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Chris Linnell's Longevity Review Newsletter - July 2024 Longevity Review 06 August 2024 - 05:01 PM

Entering the height of the summer, as soon as I post this newsletter and video, I’m going to be taking a couple of weeks off from all things longevity for the first time in more than five years. But, before I do that, I'll still bring you the latest developments in longevity, as July was a bit of a blockbuster month, or it at least had a standout study - the blocking of an inflammatory signalling molecule resulting in a massive increase of mouse health & lifespan. In Roundup, there is also an epigenetic reprogramming study for cognition, and even a lifespan extension study coming out of Canada!

In the Supplemental Section, you will find in Diet, the benefits of switching to a whole foods diet; in Exercise, long term improvement of learning via HIIT; Astaxanthin & Resveratrol for PCOS; in Combinations, Lutein/Zeaxanthin Supplements help with AMD; in Lifespan, HK extract increases mouse lifespan by 12-13%; in Microbiome, fecal transplantation improves vascular aging; in Other Ageing Biology, PEPITEM protects against inflammaging; in Reviews, a look at the effects of road traffic noise exposure; in Skin & Beauty, yet another study of the benefits of collagen; and, in Odds & Sods, improving physical performance with HBOT. Plus of course much more! (To make these suggestions easier to find, I’ve marked them with ***)

Canadian Longevity Association News

I had a meeting with my local MP, Nathaniel Erskine-Smith, to give him an update on developments in the field of longevity. He is a supporter of our mission, and gave some useful advice for when we take our advocacy to the federal government.

We also held our third Longevity Boardwalk, with the weather this time fully cooperating with some glorious sunshine. And, our online store continues to take shape - we’re getting some samples delivered, and if they’re up to scratch, we will launch!

Donate to the Canadian Longevity Association to help bring about a future where we don’t die of aging related diseases!

Please also follow, or join us on social media:

Twitter/X (I also have a personal account with more frequent longevity updates)

Facebook Instagram LinkedIn Meetup

Canadian Longevity Association YouTube Channel - where you can find video talk-throughs of these reviews.

Discord for longevity related chats and the place to have all your longevity related questions answered.

Previous newsletters can be found in the CLA Facebook Group, and also my Patreon account, which includes bonus material for supporters if you want to buy us a coffee.
Finally, we are always looking for more help or volunteers, regardless of your skill set or time availability. If you’d be interested in helping us, please fill out this Volunteer Registration Form.

July 2024 Round-Up:

This lifespan study in mice is the standout study of July, and perhaps even the year so far. It is the type of study that excites me and gives me optimism that effective longevity treatments are not too far off in our future.

The study involved both genetic knockout and pharmacological inhibition of IL-11, an inflammatory signalling molecule, and saw an increase in mouse health, such as a reduction in frailty, and a whopping 22-25% increase in median lifespan, depending on the sex and mode of treatment. This is on par with the current single intervention leader, rapamycin, but without any potential side effects. Even more promising is that drugs of this class have already passed human safety studies for pulmonary fibrosis, and could be on the market in a few years.
Mice live longer when inflammation-boosting protein is blocked Lifespan.io Analysis Full Text

Partial epigenetic reprogramming is one of the most exciting areas of longevity research, as it involves resetting gene expression to a more youthful state, and has so far shown great promise. Here is the first study showing improved cognition and memory using epigenetic reprogramming in normal, not transgenic, animals. It reduced the epigenetic age of the hippocampus and also showed a reversal of gene expressions which increase with age. It was a very small study, so did not show statistical significance, but it almost reached it, which hopefully larger studies will be able to confirm.
Cellular Reprogramming Improves Cognition in Aged Rats Full Text

Canadian Content Study

I was so thrilled to see this study, as it’s the first time I’ve seen a lifespan extension study coming out of Canada (though that doesn’t mean there haven’t been others before that I missed!).

Coming out of McGill University, this study has to do with the mitochondria, the powerhouses in our cells, and the processes of fission and fusion, which involve the break up for recycling of defective mitochondria and improved performance respectively. The authors found that increasing either fission or fusion increased worm lifespan mainly by activating multiple pathways of cellular resilience. This is very basic research, so it will be a long time before this becomes relevant to humans.
Overexpression of mitochondrial fission or mitochondrial fusion genes enhances resilience and extends longevity Full Text

Further Canadian content is indicated by CAN

Supplemental Section

Lifestyle
*New study finds 40-percent of cancer cases and almost half of all deaths in the US linked to modifiable risk factors Full Text
*Effect of Multimodal Intervention in Individuals with Mild Cognitive Impairment: A Randomized Clinical Trial in Shanghai Full Text

Fasting/Dietary Restriction – certainly the cheapest & also one of the most effective anti-ageing interventions currently available. It comes in many flavours, but I fast for at least 12 hours every day.
Extended lifespan in female Drosophila melanogaster through late-life calorie restriction Full Text
The effects of time restricted feeding on age-related changes in the mouse retina Full Text
Intermittent Fasting Targets Osteocyte Neuropeptide Y to Relieve Osteoarthritis Full Text

Diet – let food be thy medicine…
*Blood fat profiles confirm health benefits of replacing butter with high-quality plant oils Full Text
*A Switch to Whole Food Diets Benefits Elderly People Full Text***
*Unveiling the epigenetic impact of vegan vs. omnivorous diets on aging: insights from the Twins Nutrition Study (TwiNS) Full Text
Coffee consumption and cardiometabolic health: a comprehensive review of the evidence Full Text

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*Long-Term Improvement in Hippocampal-Dependent Learning Ability in Healthy, Aged Individuals Following High Intensity Interval Training Full Text***
*Dose-response relationship between physical activity and frailty: A systematic review and meta-analysis Full Text
*Effects of walking on epigenetic age acceleration: a Mendelian randomization study Full Text

Non-prescription Supplements (in alphabetical order)
NOTE - the supplements selected below are not exhaustive. They reflect what I thought were the most interesting ones back in 2019, with only a few updates since. I do individual searches for each and simply do not have time to do all others. Additionally, I’ve noticed how a lot of natural supplements affect the same genetic pathways, so I think that there is a lot of overlap and redundancy.

Astaxanthin – which is behind the pink colour of salmon & shrimp. Considered the most powerful carotenoid, it has anti-oxidative, anti-inflammatory, anti-cancer, neuro-protective and skin-protective qualities.
Astaxanthin attenuates diabetic kidney injury through upregulation of autophagy in podocytes and pathological crosstalk with mesangial cells Full Text***
*Randomized clinical trial of astaxanthin supplement on serum inflammatory markers and ER stress-apoptosis gene expression in PBMCs of women with PCOS Full Text

Curcumin – the spice which gives curries their yellow colour. Anti-inflammatory and neuroprotective. Needs to be taken with black pepper (piperine) to improve bioavailability.
*Meta-analysis of the effect of curcumin supplementation on skeletal muscle damage status Full Text
Curcumin and Gut Microbiota: A Narrative Overview with Focus on Glycemic Control Full Text
Target analysis and identification of curcumin against vascular calcification Full Text

Fisetin
The Flavonoid Fisetin Reduces Multiple Physiological Risk Factors for Dementia

Melatonin
*Effect of melatonin supplementation on cardiometabolic risk factors, oxidative stress and hormonal profile in PCOS patients: a systematic review and meta-analysis of randomized clinical trials Full Text
*Melatonin mediates intestinal barrier dysfunction and systemic inflammation in moderate-severe OSA patients Full Text
Immunoregulatory Properties of Melatonin in the Humoral Immune System: A Narrative Review Full Text

Nicotinamide MonoNucleotide (NMN)
Therapeutic effect of nicotinamide mononucleotide on Alzheimer’s disease through activating autophagy and anti-oxidative stress Full Text
NAD+ overconsumption by poly (ADP-ribose) polymerase (PARP) under oxidative stress induces cytoskeletal disruption in vascular endothelial cell Full Text

Nicotinamide Riboside (NR)
*Acute nicotinamide riboside supplementation increases human cerebral NAD+ levels in vivo Full Text
Nicotinamide riboside restores nicotinamide adenine dinucleotide levels and alleviates brain injury by inhibiting oxidative stress and neuroinflammation in a mouse model of intracerebral hemorrhage Full Text
Protective Effect of Nicotinamide Riboside on Glucocorticoid-Induced Glaucoma: Mitigating Mitochondrial Damage and Extracellular Matrix Deposition Full Text

Resveratrol
*Resveratrol ameliorates mitochondrial biogenesis and reproductive outcomes in women with polycystic ovary syndrome undergoing assisted reproduction: a randomized, triple-blind, placebo-controlled clinical trial Full Text***
Effects of resveratrol on biochemical and structural outcomes in osteoarthritis: A systematic review and meta-analysis of preclinical studies Full Text

Spermidine
Spermidine supplementation in honey bees: Autophagy and epigenetic modifications Full Text
Spermidine as an epigenetic regulator of autophagy in neurodegenerative disorders Full Text

Other available supplements or natural substances (in alphabetical order)
Alpha-ketoglutarate ameliorates age-related and surgery induced temporomandibular joint osteoarthritis via regulating IKK/NF-κB signaling Full Text
*β-Alanine supplementation improves fractional anisotropy scores in the hippocampus and amygdala in 60–80-year-old men and women Full Text
*Whole Coffee Cherry Extract Improves Working Memory and Response Inhibition: Acute and Longitudinal Results from a Remote, Randomized, Double-Blind, Placebo-Controlled Clinical Trial Full Text
*Associations of fish oil with cardiovascular disease events: results from the Taiwan longitudinal study in aging Full Text
Late-life dietary folate restriction reduces biosynthesis without compromising healthspan in mice Full Text
PDZK1 protects against mechanical overload-induced chondrocyte senescence and osteoarthritis by targeting mitochondrial function Full Text mitoQ
*Targeting aging with urolithin A in humans: A systematic review Full Text

Combinations
Medium-chain triglycerides combined with DHA improve cognitive function by inhibiting neurocyte apoptosis of the brain in SAMP8 mice Full Text
*Supplements slow disease progression during late stage of 'dry' age-related macular degeneration Abstract ***
Effectiveness and mechanisms of combined use of antioxidant nutrients in protecting against oxidative stress-induced neuronal loss and related neurological deficits Full Text
*Investigating the Effects and Mechanisms of Combined Vitamin D and K Supplementation in Postmenopausal Women: An Up-to-Date Comprehensive Review of Clinical Studies Full Text
*Metabolic effects of very-low calorie diet, Semaglutide, or combination of the two, in individuals with type 2 diabetes mellitus Full Text

Prescription Supplements

Metformin
A Mechanistic Analysis of Metformin's Biphasic Effects on Lifespan and Healthspan in C. elegans: Elixir in Youth, Poison in Elder
Metformin prevents the onset and progression of intervertebral disc degeneration: New insights and potential mechanisms (Review) Full Text
Metformin beyond type 2 diabetes: Emerging and potential new indications Full Text

Miscellaneous Molecules & Prescription Drugs
Chronic angiotensin converting enzyme inhibition attenuates frailty and protects against atrial fibrillation in aging mice CAN
*Discontinuation versus continuation of statins: A systematic review Full Text CAN
*Impact of SGLT2 Inhibitors on Very Elderly Population with Heart Failure with Reduce Ejection Fraction: Real Life Data Full Text
Age-Related Effects of AT1 Receptor Antagonist Losartan on Cognitive Decline in Spontaneously Hypertensive Rats Full Text
Empagliflozin protects against heart failure with preserved ejection fraction partly by inhibiting the senescence-associated STAT1–STING axis Full Text
*Effect of low-dose terazosin on arterial stiffness improvement: A pilot study Full Text

Novel Molecules
Nicotinamide N-methyltransferase inhibition mimics and boosts exercise-mediated improvements in muscle function in aged mice Full Text
Recombinant FOXN1 fusion protein increases T cell generation in old mice Full Text
Discovery and characterization of a new class of NAD+-independent SIRT1 activators Full Text

Other Areas of Interest (in alphabetical order)

Ageing Clocks & other biomarkers of ageing
PRC2-AgeIndex as a universal biomarker of aging and rejuvenation Full Text
Proteomic signatures improve risk prediction for common and rare diseases Full Text
Epistemic uncertainty challenges aging clock reliability in predicting rejuvenation effects Full Text

Epigenetics & Cellular Reprogramming
Strategies for modeling aging and age-related diseases Full Text
Targeting neuronal epigenomes for brain rejuvenation Full Text

Exosomes (small packets of information released by cells)
Hypoxia-Preconditioned BMSC-Derived Exosomes Induce Mitophagy via the BNIP3–ANAX2 Axis to Alleviate Intervertebral Disc Degeneration Full Text
Exosomes derived from hTERT-immortalized cells delay cellular senescence of human fibroblasts Full Text

Lifespan Lengthening Interventions
Targeting senescence induced by age or chemotherapy with a polyphenol-rich natural extract improves longevity and healthspan in mice Full Text HK Extract ***
An expedited screening platform for the discovery of anti-ageing compounds in vitro and in vivo Full Text
A Senomorphlytic Three-Drug Combination Discovered in Salsola collina for Delaying Aging Phenotypes and Extending Healthspan Full Text

Microbiome
The Gut and Skin Microbiome and Its Association with Aging Clocks Full Text
Fecal Microbiota Transfer from Young Mice Reverts Vascular Aging Hallmarks and Metabolic Impairments in Aged Mice Full Text***
*Probiotic Lactobacillus fermentum TSF331, Lactobacillus reuteri TSR332, and Lactobacillus plantarum TSP05 improved liver function and uric acid management-A pilot study Full Text

Observational Studies
*Is the relationship between chronic pain and mortality causal? A propensity score analysis Full Text CAN
*SEDENTARY BEHAVIOUR AND FALL-RELATED INJURIES IN AGING ADULTS: RESULTS FROM THE CANADIAN LONGITUDINAL STUDY ON AGING (CLSA) Full Text CAN
*Exploring the relationship between marital quality and cognitive function: A systematic review Full Text CAN
*Obesity and risk of diseases associated with hallmarks of cellular ageing: a multicohort study Full Text
*Gratitude and Mortality Among Older US Female Nurses Full Text
*Phthalate exposure and markers of biological aging: The mediating role of inflammation and moderating role of dietary nutrient intake Full Text

Opinion/Editorials/Theory
Can geroscience be translated into healthcare? Full Text
Aging and “Age-Related” Diseases - What Is the Relation? Full Text
How evolution makes us age: Introducing the evolvable soma theory of ageing

Other Ageing Biology
PEPITEM -- a novel protective agent for 'inflammageing' Full Text***
NFκB dynamics-dependent epigenetic changes modulate inflammatory gene expression and induce cellular senescence Full Text

Reproductive Health
*Hormone therapy is associated with lower Alzheimer’s disease tau biomarkers in post-menopausal females -evidence from two independent cohorts Full Text CAN
*Antioxidants and Fertility in Women with Ovarian Ageing: a Systematic Review and Meta-Analysis Full Text
FOXO4-DRI improves spermatogenesis in aged mice through reducing senescence-associated secretory phenotype secretion from Leydig cells Full Text

Reviews
Road traffic noise exposure and its impact on health: evidence from animal and human studies—chronic stress, inflammation, and oxidative stress as key components of the complex downstream pathway underlying noise-induced non-auditory health effects Full Text***
Extraordinary model systems for regeneration Full Text
Natural Compounds for Preventing Age-Related Diseases and Cancers Full Text
The influence of sex-specific factors on biological transformations and health outcomes in aging processes Full Text

Senolytics/Senescent Cells
Inhibitory immune checkpoints suppress the surveillance of senescent cells promoting their accumulation with aging and in age-related diseases Full Text
Procyanidin C1 inhibits bleomycin-induced pulmonary fibrosis in mice by selective clearance of senescent myofibroblasts Full Text
*Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial

Skin & Beauty
*Senomorphic activity of a combination of niacinamide and hyaluronic acid: correlation with clinical improvement of skin aging Full Text
*A Clinical Trial Shows Improvement in Skin Collagen, Hydration, Elasticity, Wrinkles, Scalp, and Hair Condition following 12-Week Oral Intake of a Supplement Containing Hydrolysed Collagen Full Text***
Triethylene Glycol Squalene Improves Hair Regeneration by Maintaining the Inductive Capacity of Human Dermal Papilla Cells and Preventing Premature Aging

Stem Cells
11β hydroxysteroid dehydrogenase type 1 transgenic mesenchymal stem cells attenuate inflammation in models of sepsis Full Text
Three-dimensional cultured human umbilical cord mesenchymal stem cells attenuate pulmonary fibrosis by improving the balance of mitochondrial fusion and fission Full Text

Telomeres
*Pharmacotherapeutic Considerations on Telomere Biology: The Positive Effect of Pharmacologically Active Substances on Telomere Length Full Text
*The association of metabolic syndrome with telomere length as a marker of cellular aging: a systematic review and meta-analysis Full Text
*Association between telomere length and erectile dysfunction: a cross-sectional study Full Text

Odds & Sods
*The lifelong orgasm gap: exploring age’s impact on orgasm rates Full Text
*Physical enhancement of older adults using hyperbaric oxygen: a randomized controlled trial Full Text***
Feline Cognition and the Role of Nutrition: An Evolutionary Perspective and Historical Review Full Text
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***Disclaimer 1 – I am NOT a doctor or indeed a scientist. All the information pertained within is for information purposes only; use at your own risk. Please consult with a healthcare practitioner if you need medical advice.***

**Disclaimer 2 – In no way should supplements be a replacement for an unhealthy diet or lifestyle. A varied, plant dominant dietary pattern is the cornerstone for health. Try to eat the rainbow – the greater the variety, the greater the benefit. Even though I might take a supplement derived from a plant source, I still eat the plant in question. Also, make sure you move as much as possible – that is what we evolved to do.**

*Also bear in mind that most of the studies mentioned above are in rodents, not humans. Rodents, needless to say, do not always react the same way to drugs as humans do – witness the countless times cancer or another disease has been cured in rodents only to subsequently fail human trials. I have *starred any human trials.*
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Chris Linnell's Longevity Review Newsletter - June 2024 Longevity Review 29 July 2024 - 08:45 PM

With summer in full swing, we will take a look at how early Alzheimer’s could be slowed, stopped or even reversed through extensive lifestyle changes; how CRISPR gene therapy could be used to repair damaged organs; the first lifespan study of NMN; a look at Longevity Summit Dublin; and, how natural antioxidants could prevent the loss of testosterone in older men in the Canadian Content Study.

In the supplemental section you will find in Exercise, how heavy resistance training can have long lasting effects; in Nicotinamide Riboside (NR) how it improves walking in a human trial; In Other Supplements, how Taurine reduces the risk of metabolic syndrome; in Microbiome, how probiotics improve cognition and inflammation; in Observational Studies, how 70 is the new 60; in Skin & Beauty, a couple more studies on the benefits of collagen; and in Odds and Sods, how organic light-emitting diode therapy promotes longevity. Plus of course much more!

Canadian Longevity Association News

The big news this month is that we launched the first phase of our website update! The website had been relatively unchanged for the past two years due to a lack of resources, but we’ve now finally made some changes to improve its look and content. It is still very much a work in progress, but should see further improvements as the year progresses. Please take a look and tell us what you think!

We have started the process of creating our online merchandise store, so you will soon be able to purchase CLA branded items such as T-shirts, coffee mugs etc. It’s important for us to get more revenue so that we can do more to advocate for longevity, and ultimately improve YOUR health and wellbeing.

We held our second monthly Longevity Walk along the Boardwalk, which was once again marred by a rainy forecast, but also once again, by the time we left on the walk, the heavens had cleared.

Chris Linnell's Longevity Review Newsletter - May 2024 Longevity Review 30 June 2024 - 07:38 PM

As we transition towards summer you will find in this month’s Longevity Review, a study showing that senolytics might already be in widespread use; further proof of the mortality benefits of the Mediterranean diet; a Canadian study showing how increased protein intake boosts muscle building in the elderly; news from a longevity conference and a heavyweight debate on the path forward for longevity.
In the supplemental section you will find in Fasting, how intermittent fasting improves gut health; in Exercise, how exercise acts as a senolytic; in Combinations, a pair of studies showing synergistic effects between vitamin D intake and physical activity; in Genetics, a gene therapy for dementia; in Lifespan, the latest Interventions Testing Program results; in Other Ageing Biology, how the naked mole rat continues to defy the law of mortality; in Skin & Beauty, successful skin care trials; in Stem Cells, a therapy for low grade inflammation; and in Odds & Sods, more studies on the benefits of hyperbaric oxygen therapy. And, of course, much more!

Canadian Longevity Association News

We had our first in-person event of the year, with a longevity walk along the boardwalk in Toronto. Although the weather didn’t start off being cooperative, by the time the walk started, the heavens had cleared and it turned out to be nice and sunny so that good times were had by all.
We also had another volunteer join our ever expanding team - welcome Mike Cottrill!

Donate to the Canadian Longevity Association to help bring about a future where we don’t die of aging related diseases!

Please also follow, or join us on social media:

Twitter/X (I also have a personal account with more frequent longevity updates)

Facebook Instagram LinkedIn Meetup

Canadian Longevity Association YouTube Channel - where you can find video talk-throughs of these reviews.

Discord for longevity related chats and the place to have all your longevity related questions answered.

May 2024 Round-Up:

Are millions of people already taking senolytics? That is the intriguing question posed by this paper which posits that SGLT2 inhibitors, used to treat diabetes, heart failure and chronic kidney disease, also act as an indirect senolytic. The evidence appears to be that this is true, which opens up the possibility of expanding their indications to treat aging more generally.
SGLT2 inhibition eliminates senescent cells and alleviates pathological aging Full Text

By now we should all be aware of the health benefits of the Mediterranean diet, with countless studies to back up that claim. However, most of those studies were over short timeframes, not exceeding a few years. This study, on the other hand, tracked 25K women over 25 years and found that those who more closely followed the diet had a 23% lower risk of mortality than those who didn’t.
*Mediterranean Diet Adherence and Risk of All-Cause Mortality in Women Full Text

One of the first major longevity conferences of the year, the Rejuvenation Startup Summit, took place in Berlin in May, with numerous talks from researchers and biotechs working on longevity. You can read more about it in this detailed write up from Lifespan.io. You can also check out the videos of the talks, which have begun to be posted on YouTube.
“Everything Happens in Berlin”: Highlights from the Summit
Rejuvenation Startup Summit Videos

There was also a highly anticipated debate between Aubrey de Grey and Peter Fedichev, over the best strategy to defeat aging with (in simplistic terms) Aubrey arguing for reversal, while Peter argued for a halting of the aging process. There was a $10K prize for the winner.
How to Defeat Aging? Two Scientists Offer Their Visions
Debate Video

Canadian Content Study

The importance of having enough muscle mass when you age cannot be overstated - the lower the muscle mass, the greater the risk of frailty and ultimately, mortality. But, how to achieve that? Apart from resistance training, adequate protein intake is essential. In fact, older people need substantially more than younger adults as they don’t synthesize it as effectively.

This study, from McMaster University, looked at giving older men an additional 50 grams of protein over the recommended daily amount (0.8g/kg) in the form of whey, pea or collagen protein to be consumed over breakfast and lunch. This resulted in a 9% increase in protein synthesis for both whey and pea protein, but not for collagen.
*The effects of whey, pea, and collagen protein supplementation beyond the recommended dietary allowance on integrated myofibrillar protein synthetic rates in older males: a randomized controlled trial Full Text

Other Canadian studies can be found marked as CAN throughout this newsletter.

Supplemental Section

Lifestyle
*Protein Intake and Physical Activity Levels as Determinants of Sarcopenia Risk in Community-Dwelling Older Adults Full Text
*Epigenetic Age Mediates the Association of Life's Essential 8 With Cardiovascular Disease and Mortality Full Text
*Physical activity and fiber intake beneficial for muscle mass and strength preservation during aging: A comprehensive cross-sectional study in the UK biobank cohort Full Text

Fasting/Dietary Restriction – certainly the cheapest & also one of the most effective anti-ageing interventions currently available. It comes in many flavours, but I fast for at least 12 hours every day.
*Intermittent fasting shows promise in improving gut health, weight management Full Text
Intermittent fasting protects against liver inflammation and liver cancer Full Text
*Effect of time-restricted eating and intermittent fasting on cognitive function and mental health in older adults: A systematic review Full Text

Diet – let food be thy medicine…
*Dietary protein and amino acid intakes for mitigating sarcopenia in humans Full Text
*Association of coffee and tea consumption with osteoporosis risk: A prospective study from the UK biobank
*Effect of Food Groups on Aging in Older Women
*Identifying the relation between food groups and biological ageing: a data-driven approach Full Text

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*Exercise May Remove Senescent Cells Through Inflammation Full Text
*Effects of physical exercise on neuromuscular junction degeneration during ageing: A systematic review Full Text
Potential molecular mechanism of exercise reversing insulin resistance and improving neurodegenerative diseases Full Text

Astaxanthin – which is behind the pink colour of salmon & shrimp. Considered the most powerful carotenoid, it has anti-oxidative, anti-inflammatory, anti-cancer, neuro-protective and skin-protective qualities.
*Comparative Pharmacokinetic Study of Standard Astaxanthin and its Micellar Formulation in Healthy Male Volunteers Full Text
Protective effects of astaxanthin on particulate matter 2.5‑induced senescence in HaCaT keratinocytes via maintenance of redox homeostasis Full Text

Curcumin – the spice which gives curries their yellow colour. Anti-inflammatory and neuroprotective. Needs to be taken with black pepper (piperine) to improve bioavailability.
*Effect of nano-curcumin supplementation on angina status, and traditional and novel cardiovascular risk factors in overweight or obese patients with coronary slow flow phenomenon: a randomized double-blind placebo-controlled clinical trial Full Text
*Effects of curcumin in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis Full Text

Fisetin
*Clinical validation of C12FDG as a marker associated with senescence and osteoarthritic phenotypes Full Text

Melatonin
Melatonin promotes hair regeneration by modulating the Wnt/β-catenin signalling pathway Full Text
*Clinical Studies Using Topical Melatonin Full Text

Nicotinamide MonoNucleotide (NMN)
Integrated transcriptome and metabolome study reveal the therapeutic effects of nicotinamide riboside and nicotinamide mononucleotide on nonalcoholic fatty liver disease Full Text & NR
Toxicology study profile of Nicotinamide mononucleotide after acute and 90-day sub chronic dosing in Wistar rats and mutagenicity tests Full Text
*Ingestion of β-nicotinamide mononucleotide increased blood NAD levels, maintained walking speed, and improved sleep quality in older adults in a double-blind randomized, placebo-controlled study

Nicotinamide Riboside (NR)
Nicotinamide riboside attenuates myocardial ischemia-reperfusion injury via regulating SIRT3/SOD2 signaling pathway Full Text
Hepatic steatosis induced by nicotine plus Coca-Cola™ is prevented by nicotinamide riboside (NR) Full Text

Resveratrol
SIRT1, resveratrol and aging Full Text

Other available supplements or natural substances (in alphabetical order)
Potential Effects of Traditional Chinese Medicine in Anti-Aging and Aging-Related Diseases: Current Evidence and Perspectives Full Text
Real-world Chinese herbal medicine for Parkinson's disease: a hospital-based retrospective analysis of electronic medical records Full Text
*Emerging Roles of Vitamin B12 in Aging and Inflammation Full Text
The evidence to date: implications of l-ascorbic acid in the pathophysiology of aging Full Text
Why One Antioxidant Might Alleviate Disc Degeneration Full Text
Quercetin promotes the proportion and maturation of NK cells by binding to MYH9 and improves cognitive functions in aged mice Full Text
*The effects of omega-3 polyunsaturated fatty acids on muscle and whole-body protein synthesis: a systematic review and meta-analysis Full Text
Urolithin A improves Alzheimer's disease cognition and restores mitophagy and lysosomal functions Full Text

Combinations
*Synergistic impact of 25-hydroxyvitamin D concentrations and physical activity on delaying aging Full Text
*Association of physical activity and vitamin D deficiency with cognitive impairment in older adults: a population based cross-sectional analysis Full Text
A cocktail of rapamycin, acarbose, and phenylbutyrate prevents age-related cognitive decline in mice by targeting multiple aging pathways Full Text
Docosahexaenoic Acid (DHA), Vitamin D3, and Probiotics Supplementation Improve Memory, Glial Reactivity, and Oxidative Stress Biomarkers in an Aluminum-Induced Cognitive Impairment Rat Model Full Text
A randomized, controlled clinical trial demonstrates improved owner-assessed cognitive function in senior dogs receiving a senolytic and NAD+ precursor combination Full Text

Prescription Supplements

Metformin
*Metformin mitigates dementia risk among individuals with type 2 diabetes Full Text

Rapamycin (sirolimus)
Inhibition of mTOR prevents glucotoxicity-mediated increase of SA-beta-gal, p16INK4a, and insulin hypersecretion, without restoring electrical features of mouse pancreatic islets Full Text

Miscellaneous Molecules & Prescription Drugs
Intermittent glucocorticoid treatment improves muscle metabolism via the PGC1α/Lipin1 axis in an aging-related sarcopenia model Full Text
Hydroxycitrate delays early mortality in mice and promotes muscle regeneration while inducing a rich hepatic energetic status Full Text
SGLT2 inhibition to target kidney aging Full Text
Hypothalamic sex-specific metabolic shift by canagliflozin during aging Full Text

Novel Molecules
Small-molecule-induced epigenetic rejuvenation promotes SREBP condensation and overcomes barriers to CNS myelin regeneration

Other Areas of Interest (in alphabetical order)

Ageing Clocks & other biomarkers of ageing
How biological aging clocks tick Full Text
Quantifying the stochastic component of epigenetic aging Full Text
*Proteomic aging clock (PAC) predicts age-related outcomes in middle-aged and older adults Full Text
*The effect of epigenetic aging on neurodegenerative diseases: a Mendelian randomization study Full Text

Blood Factors or other Heterochronic Transplantation
Young blood-mediated cerebromicrovascular rejuvenation through heterochronic parabiosis: enhancing blood-brain barrier integrity and capillarization in the aged mouse brain
Long-term hematopoietic transfer of the anti-cancer and lifespan-extending capabilities of a genetically engineered blood system by transplantation of bone marrow mononuclear cells Full Text

Epigenetics & Cellular Reprogramming
A youthful touch: Reversal of aging hallmarks by cell reprogramming Full Text

Exosomes (small packets of information released by cells)
Strategies in product engineering of mesenchymal stem cell-derived exosomes: unveiling the mechanisms underpinning the promotive effects of mesenchymal stem cell-derived exosomes Full Tex
Mesenchymal Stem Cells-based Cell-free Therapy Targeting Neuroinflammation Full Text

Genetics including CRISPR
Emerging technology has a brilliant future: the CRISPR-Cas system for senescence, inflammation, and cartilage repair in osteoarthritis Full Text
*Progranulin AAV gene therapy for frontotemporal dementia: translational studies and phase 1/2 trial interim results Full Text
*Genetic effects and causal association analyses of 14 common conditions/diseases in multimorbidity patterns Full Text

Lifespan Lengthening Interventions
Lifespan effects in male UM-HET3 mice treated with sodium thiosulfate, 16-hydroxyestriol, and late-start canagliflozin
Targeting CK2 eliminates senescent cells and prolongs lifespan in Zmpste24-deficient mice Full Text
Translatability of life-extending pharmacological treatments between different species Full Text
Low-dose naltrexone extends healthspan and lifespan in C. elegans via SKN-1 activation Full Text

Microbiome
Enhancing probiotic impact: engineering Saccharomyces boulardii for optimal acetic acid production and gastric passage tolerance Full Text
Oral Administration of Bifidobacterium lactis Ameliorates Cognitive Deficits in Mice Intracerebroventricularly Administered Amyloid Beta via Regulation the Activation of Mitogen-activated Protein Kinases Full Text
*Association of the oral microbiome with cognitive function among older adults: NHANES 2011–2012 Full Text

Observational Studies
*Arthritis is associated with high nutritional risk among older Canadian adults from the Canadian Longitudinal Study on Aging Full Text CAN
*Short communication: Lifetime musical activity and resting-state functional connectivity in cognitive networks Full Text
*Circulating microRNA profile of long-lived Okinawans identifies novel potential targets for optimizing lifespan and health span Full Text
*Predictive values of relative fat mass and body mass index on cardiovascular health in community-dwelling older adults: Results from the Longevity Check-up (Lookup) 7+ Full Text

Opinion/Editorials/Theory
Gerogenes and gerosuppression: the pillars of precision geromedicine Full Text May
The beginning of becoming a human Full Text
Successful Aging and Subjective Aging: Toward a Framework to Research a Neglected Connection Full Text
Psychogenic Aging: A Novel Prospect to Integrate Psychobiological Hallmarks of Aging Full Text

Other Ageing Biology
Identification and characterization of small molecule inhibitors of the LINE-1 retrotransposon endonuclease Full Text
Intracellular cytokines in peritoneal leukocytes relate to lifespan in aging and long-lived female mice Full Text
Trio preserves motor synapses and prolongs motor ability during aging Full Text
Five years later, with double the demographic data, naked mole-rat mortality rates continue to defy Gompertzian laws by not increasing with age Full Text

Reproductive Health
*Examining the Effects of Nutrient Supplementation on Metabolic Pathways via Mitochondrial Ferredoxin in Aging Ovaries Full Text
Expert Consensus on Prevention and Treatment of Aging-Related Gonadal Dysfunction Full Text
Preservation of ovarian function using human pluripotent stem cell-derived mesenchymal progenitor cells Full Text
*The efficacy of oral Lavandula angustifolia Mill. essential oil on menopausal symptoms, serum lipid profile, and cortisol concentration in postmenopausal women: A triple-blind, randomized, controlled trial Full Text

Reviews
Impact of Aging on Cardiovascular Diseases: From Chronological Observation to Biological Insights: JACC Family Series Full Text
Molecular mechanisms of aging and anti-aging strategies Full Text
Physical Activity and Oxidative Stress in Aging Full Text

Senolytics/Senescent Cells
Senolytics and cell senescence: historical and evolutionary perspectives Full Text
Senolytic combination of dasatinib and quercetin attenuates renal damage in diabetic kidney disease Full Text
Failure of senolytic treatment to prevent cognitive decline in a female rodent model of aging Full Text
The potential for senotherapy as a novel approach to extend life quality in veterinary medicine Full Text

Skin & Beauty
*Anti-aging Effects of Tirbanibulin 1% Ointment: A Real-Life Experience Full Text
*Beneficial Effects of Multi-Micronutrient Supplementation with Collagen Peptides on Global Wrinkles, Skin Elasticity and Appearance in Healthy Female Subjects Full Text
*Low-level laser therapy for skin rejuvenation: A safe and effective solution baked by data and visual evidence Full Text

Stem Cells
*Safety and efficacy of autologous adipose tissue-derived stem cell transplantation in aging-related low-grade inflammation patients: a single-group, open-label, phase I clinical trial Full Text
Dental pulp stem cells ameliorate D-galactose-induced cardiac ageing in rats Full Text
Rejuvenation of peripheral immune cells attenuates Alzheimer’s disease-like pathologies and behavioral deficits in a mouse model Full Text

Telomeres
Elevated tissue status of omega-3 fatty acids protects against age-related telomere attrition in fat-1 transgenic mice Full Text

Chris Linnell's Longevity Review Newsletter - April 2024 Longevity Review 16 May 2024 - 06:26 PM

In this month’s Longevity Review you will find how small extracellular vesicles, which cells use to communicate with each other, can increase lifespan in mice; how stem cells taken from umbilical cords can help with frailty in humans; the best time of day to exercise to reduce your mortality if you suffer from obesity or diabetes; and, in the Canadian Content section, how the nuclear envelope is more dynamic than initially thought, and helps repair DNA damage.

In the supplemental section you will find, under exercise, the effects of different intensities of resistance training; in additional supplements, two reviews of vitamin D and one of magnesium; in opinion an interesting piece on how we need a new discipline of juventology; in reproduction, a number of ways to delay Ovarian aging using stem cells, NMN, NR & quercetin; and, in stem cells, how transplanting mitochondria can improve muscle function. In addition, there are a record six Canadian studies in this edition, marked by CAN. Plus of course much more!

Canadian Longevity Association News

We onboarded two more volunteers who will help with content creation for the website and help with cybersecurity - welcome aboard Brennan and Mike! Please consider bringing your own unique skills to help us and join our growing team.

We have also finally started work on improving and expanding our website. Some initial changes will soon be going live.

Donate to the Canadian Longevity Association to help bring about a future where we don’t die of aging related diseases!

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April 2024 Round-Up:
In this study, small extracellular vesicles (sEVs)(small packets of chemical information cells use to communicate with each other) from young male mice extended the average lifespan of old male mice by 12% - a considerable amount considering treatment only started in old age. In addition, various physiological functions improved, including fertility. Additionally, this treatment seemed to cross the species barrier as sEVs taken from younger human males had a similar effect on the mice, which indicates, if the reverse held true, that we might be able to get an abundant source of young sEVs from farm animals for example.
Young Extracellular Vesicles Extend Life in Old Mice Full Text

Further showing the potential of sEVs and their ilk, this small human study of umbilical cord stem cells improved various parameters of frailty in elderly Chinese, which improved their quality of life. I link this to sEVs as the main benefit of stem cells derives from the substances they excrete, sEVs among them, as the cells themselves do not last long in the body.
*Stem Cells Alleviate Frailty in Clinical Trial Full Text

Here is a very actionable association study using data from the UK Biobank. For older people with obesity, the best time of day to perform moderate to vigorous physical activity was in the evenings, with a whopping 61% reduction in mortality compared to those who did not exercise. This was considerably better than exercising in the morning or afternoon, though any time of day is better than none.
*Evening Aerobic Exercise Associated with Least Mortality Full Text

Canadian Content Highlight
In this groundbreaking study from the lab of University of Toronto professor Dr. Karim Mekhail, they showed that the envelope which surrounds the nucleus in our cells is actively involved in the repair of DNA damage. Although this paper mainly concentrates on the effects on cancer, they also briefly touch on progeria and by extension, aging. The lab is actively pursuing studies related to this on aging, including means to reverse changes to the envelope with age.
Toronto researchers uncover human DNA repair by nuclear metamorphosis
Team effort reveals cells reshape their nucleus to repair DNA, impacting cancer and aging
DNA double-strand break–capturing nuclear envelope tubules drive DNA repair Abstract
Full Text

Supplemental Section

Lifestyle
*Protein-enriched soup and weekly exercise improve muscle health: A randomized trial in mid-to-old age with inadequate protein intake Full Text
*Association between Life’s Essential 8 and cognitive function: insights from NHANES 2011–2014 Full Text
*Lifestyle-related factors in late midlife as predictors of frailty from late midlife into old age: a longitudinal birth cohort study Full Text

Fasting/Dietary Restriction – certainly the cheapest & also one of the most effective anti-ageing interventions currently available. It comes in many flavours, but I fast for at least 12 hours every day.
*Effect of calorie restriction and intermittent fasting on glucose homeostasis, lipid profile, inflammatory, and hormonal markers in patients with polycystic ovary syndrome: a systematic review Full Text
*Neuroprotective effects of intermittent fasting in the aging brain Full Text
*Effect of Isocaloric, Time-Restricted Eating on Body Weight in Adults With Obesity: A Randomized Controlled Trial

Diet – let food be thy medicine…
*The association of the dietary inflammatory potential with risk of overall and site-specific cancers: A community-based longitudinal study in the UK Biobank Full Text
*Wild Blueberry Extract Intervention in Healthy Older Adults: A Multi-Study, Randomised, Controlled Investigation of Acute Cognitive and Cardiovascular Effects Full Text
*Alcohol consumption and accelerated biological ageing in middle-aged and older people: A longitudinal study from two cohorts

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*Effect of resistance circuit training on comprehensive health indicators in older adults: a systematic review and meta-analysis Full Text
*Presence of specific lipids indicate tissue ageing and can be decreased through exercise Full Text

Curcumin – the spice which gives curries their yellow colour. Anti-inflammatory and neuroprotective. Needs to be taken with black pepper (piperine) to improve bioavailability.
*Patient-reported outcomes of curcumin supplementation in rheumatoid arthritis and psoriatic arthritis: a cross-sectional survey
*The efficacy of curcumin in relieving osteoarthritis: A meta-analysis of meta-analyses
Advancing Gastrointestinal Health: Curcumin’s Efficacy and Nanopreparations Full Text
Curcumin attenuates brain aging by reducing apoptosis and oxidative stress
*Curcumin as a Multifunctional Spice Ingredient against Mental Disorders in Humans: Current Clinical Studies and Bioavailability Concerns Full Text

Melatonin
A Clinical, Pharmacological, and Formulation Evaluation of Melatonin in the Treatment of Ocular Disorders—A Systematic Review Full Text
*The Positive Association between Melatonin-Containing Food Consumption and Older Adult Life Satisfaction, Psychoemotional State, and Cognitive Function Full Text
Antioxidant Actions of Melatonin: A Systematic Review of Animal Studies Full Text

Nicotinamide MonoNucleotide (NMN)
A Magnesium Binding Site And The Anomeric Effect Regulate The Abiotic Redox Chemistry Of Nicotinamide Nucleotides Full Text CAN
LXR/CD38 activation drives cholesterol-induced macrophage senescence and neurodegeneration via NAD+ depletion Full Text

Pterostilbene
Pterostilbene Protects against Osteoarthritis through NLRP3 Inflammasome Inactivation and Improves Gut Microbiota as Evidenced by In Vivo and In Vitro Studies Full Text

Resveratrol
Resveratrol alleviates acute lung injury in mice by promoting Pink1/Parkin-related mitophagy and inhibiting NLRP3 inflammasome activation Full Text
Exploring the multimodal health-promoting properties of resveratrol: A comprehensive review Full Text
Potential role of resveratrol in prevention and therapy of diabetic complications: a critical review Full Text

Other available supplements or natural substances (in alphabetical order)
Comparing the efficacy of concomitant treatment of resistance exercise and creatine monohydrate versus multiple individual therapies in age related sarcopenia Full Text
*Consensus Statement on Vitamin D Status Assessment and Supplementation: Whys, Whens, and Hows Full Text
*The Power of Vitamin D: Is the Future in Precision Nutrition through Personalized Supplementation Plans? Full Text
L-Ergothioneine slows the progression of age-related hearing loss in CBA/CaJ mice
Association between dietary magnesium intake, inflammation, and neurodegeneration Full Text
*The efficacy and safety of Nigella sativa in the management of osteoarthritis: A systematic review Full Text
*Improvement in Visceral Adipose Tissue and LDL Cholesterol by High PUFA Intake: 1-Year Results of the NutriAct Trial Full Text
Methylated urolithin A, mitigates cognitive impairment by inhibiting NLRP3 inflammasome and ameliorating mitochondrial dysfunction in aging mice

Combinations
*The effect of curcumin and high-content eicosapentaenoic acid supplementations in type 2 diabetes mellitus patients: a double-blinded randomized clinical trial Full Text
*Effects of vitamin D3, omega-3 s and a simple strength training exercise program on bone health: the DO-HEALTH randomized controlled trial Full Text
Combined Metabolic Activators with Different NAD+ Precursors Improve Metabolic Functions in the Animal Models of Neurodegenerative Diseases Full Text

Prescription Supplements

Metformin
Causal association of metformin treatment with diverse cardiovascular diseases: a Mendelian randomization analysis Full Text

Rapamycin (sirolimus)
*Evaluating the effect of rapamycin treatment in Alzheimer’s disease and aging using in vivo imaging: the ERAP phase IIa clinical study protocol Full Text
Effect and Mechanism of Rapamycin on Cognitive Deficits in Animal Models of Alzheimer's Disease: A Systematic Review and Meta-analysis of Preclinical Studies

Miscellaneous Molecules & Prescription Drugs
Transcriptome-based deep learning analysis identifies drug candidates targeting protein synthesis and autophagy for the treatment of muscle wasting disorder Full Text
Canagliflozin inhibits PASMCs proliferation via regulating SGLT1/AMPK signaling and attenuates artery remodeling in MCT-induced pulmonary arterial hypertension Full Text
Itaconate alleviates anesthesia/surgery-induced cognitive impairment by activating a Nrf2-dependent anti-neuroinflammation and neurogenesis via gut-brain axis Full Text
Doxycycline decelerates aging in progeria mice Full Text
GLP-2 ameliorates D-galactose induced muscle aging by IGF-1/Pi3k/Akt/FoxO3a signaling pathway in C2C12 cells and mice Full Text

Novel Molecules
BRD2-specific inhibitor, BBC0403, inhibits the progression of osteoarthritis pathogenesis in osteoarthritis-induced C57BL/6 male mice Full Text

Other Areas of Interest (in alphabetical order)

Ageing Clocks & other biomarkers of ageing
*Aging Measurements Can Vary by Time of Day Full Text
*A Comparison of 5 Measures of Accelerated Biological Aging and Their Association With Incident Cardiovascular Disease: The CARDIA Study Full Text
*Accelerated epigenetic age is associated with whole-brain functional connectivity and impaired cognitive performance in older adults Full Text

Epigenetics & Cellular Reprogramming
Nonlinear DNA methylation trajectories in aging male mice Full Text
*Very Long-Lived People Have Protected Epigenetics
*Methylation entropy landscape of Chinese long-lived individuals reveals lower epigenetic noise related to human healthy aging Full Text

Exosomes (small packets of information released by cells)
Stem cell secretome treatment improves whole-body metabolism, reduces adiposity, and promotes skeletal muscle function in aged mice Full Text
The complexity of extracellular vesicles: Bridging the gap between cellular communication and neuropathology Full Text CAN
Young osteocyte-derived extracellular vesicles facilitate osteogenesis by transferring tropomyosin-1 Full Text

Genetics including CRISPR
*Cognitively healthy centenarians are genetically protected against Alzheimer's disease Full Text
*Polygenic markers of survival and longevity in the antioxidant genes PON1, PON2, MTHFR, MSRA, SOD1, NQO1, and CAT in a 20-year follow-up study in the population from the Volga-Ural region

Lifespan Lengthening Interventions
Low-Molecular Weight Compounds that Extend the Chronological Lifespan of Yeasts, Saccharomyces cerevisiae, and Schizosaccharomyces pombe Full Text
A Re-Analysis Finds Potential Life-Prolonging Compounds Full Text

Microbiome
*Oral microbial signatures associated with age and frailty in Canadian adults Full Text CAN
Polyphenolic Compounds: Orchestrating Intestinal Microbiota Harmony during Aging Full Text
*Age and aging process alter the gut microbes Full Text

Observational Studies
*Associations Between Age at Menopause, Vascular Risk, and 3-Year Cognitive Change in the Canadian Longitudinal Study on Aging CAN
*Serum klotho levels and mortality patterns in frail individuals: unraveling the u-shaped association Full Text
*The prognostic value of serum α-klotho in age-related diseases among the US population: A prospective population-based cohort study Full Text
*Systolic Blood Pressure and Survival to Very Old Age: Results From the Women’s Health Initiative Full Text
*Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021 Full Text
*People think 'old age' starts later than it used to, study finds Abstract

Opinion/Editorials/Theory
Exploring juventology: unlocking the secrets of youthspan and longevity programs Full Text
Ageing as a two-phase process: theoretical framework Full Text
NIA Translational Geroscience Network: An infrastructure to facilitate geroscience-guided clinical trials Full Text

Other Ageing Biology
Identification of prospective aging drug targets via Mendelian randomization analysis Full Text
The coupling between healthspan and lifespan in Caenorhabditis depends on complex interactions between compound intervention and genetic background Full Text
Predictive Models of Life Span in Old Female Mice Based on Immune, Redox, and Behavioral Parameters Full Text
Mitochondria Injection Alleviates Parkinson’s in Mice
Mitochondrial transplantation exhibits neuroprotective effects and improves behavioral deficits in an animal model of Parkinson's disease Full Text

Regenerative Medicine
Regeneration of Nonhuman Primate Hearts With Human Induced Pluripotent Stem Cell–Derived Cardiac Spheroids Full Text

Reproductive Health
Efficacy and safety of mesenchymal stem cell therapy for ovarian ageing in a mouse model Full Text
NMN and NR Reverse Ovarian Aging in Rats Full Text
*The impact of resveratrol on the outcome of the in vitro fertilization: an exploratory randomized placebo-controlled trial Full Text
Quercetin Delays Ovarian Aging in Middle-Aged Mice Full Text

Reviews
Genetic, Environmental, and Stochastic Components of Lifespan Variability: The Drosophila Paradigm Full Text
Will cellular immunotherapies end neurodegenerative diseases? Full Text
How does a fly die? Insights into ageing from the pathophysiology of Drosophila mortality Full Text

Senolytics/Senescent Cells
Chemical Strategies for the Detection and Elimination of Senescent Cells Full Text
Senescence and senolysis in cancer: The latest findings Full Text
Cellular Senescence as a Targetable Risk Factor for Cardiovascular Diseases: Therapeutic Implications: JACC Family Series Full Text

Skin & Beauty
Discovery of a novel and highly selective JAK3 inhibitor as a potent hair growth promoter Full Text
*Exosomes and Signaling Nanovesicles from the Nanofiltration of Preconditioned Adipose Tissue with Skin-B® in Tissue Regeneration and Antiaging: A Clinical Study and Case Report Full Text
*Use of platelet rich plasma for skin rejuvenation Full Text

Stem Cells
Rebuilding and rebooting immunity with stem cells Full Text CAN
Transplanting Mitochondria Improves Muscle Function Full Text
The Effect of Short-Term NAD3® Supplementation on Circulating Adult Stem Cells in Healthy Individuals Aged 40-70 Years Full Text

Telomeres
*Telomeres and aging: on and off the planet! Full Text
New insights from bidirectional Mendelian randomization: causal relationships between telomere length and mitochondrial DNA copy number in aging biomarkers Full Text
*Genetic susceptibility to chronic diseases leads to heart failure among Europeans: the influence of leukocyte telomere length Full Text

Odds & Sods
Hyperbaric oxygen therapy promotes the browning of white fat and contributes to the healing of diabetic wounds Full Text
*Cannabis smoking is associated with advanced epigenetic age Full Text
FNDC5/irisin mediates the protective effects of Innovative theta-shaking exercise on mouse memory Full Text
*Effect of whole-body vibration stimulation on plasma soluble TNF receptors in elderly with sarcopenia: a randomized controlled trial Full Text
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***Disclaimer 1 – I am NOT a doctor or indeed a scientist. All the information pertained within is for information purposes only; use at your own risk. Please consult with a healthcare practitioner if you need medical advice.***

Chris Linnell's Longevity Review Newsletter - March 2024 Longevity Review 14 April 2024 - 05:27 PM

As winter enters the rearview mirror, March’s highlights included three lifespan extending studies involving young blood plasma, a two drug synergistic combo and the main bioactive molecule found in mushrooms, and the Canadian content section returns with a groundbreaking study leveraging the powers of AI for drug development.

In addition to the above you will also find under NMN, a study showing it improves the lifespan of age accelerated mice; in Other Supplements, reviews of Apigenin and Kaempferol; in Epigenetics, an examination of chemical partial reprogramming; in Reproductive Health, two studies using stem cells to preserve ovarian function; in Skin & Beauty, two studies on the benefits of of taking collagen; and, at the very end in Odds & Sods, you can find a write up of the recent longevity network state of Vitalia and how, with the Million Molecule Challenge, you can help discover new longevity molecules. Plus of course much more!

Canadian Longevity Association News

We onboarded a new volunteer who has some skills with AI and is using them to help automate some of our processes, which will give us more time to work on more important stuff. Welcome aboard Barzin!

Our team is slowly but surely growing, and with each additional member and skillset, we will be able to accomplish more. Please consider joining our team to help us make even further progress.

Donate to the Canadian Longevity Association to help bring about a future where we don’t die of aging related diseases!

Please also follow, or join us on social media:

Twitter/X (I also have a personal account with more frequent longevity updates)

Facebook Instagram LinkedIn Meetup

Canadian Longevity Association YouTube Channel - where you can find video talk-throughs of these reviews.

Discord for longevity related chats and the place to have all your longevity related questions answered.

March 2024 Round-Up:

This is the first published study showing that young blood plasma can potentially extend the lifespan of a rat. I say potentially as this was a very small study, and one of the controls had the longest lifespan overall. However, the methylation age of the treated rats was also reduced, they supposedly showed more activity and their fur had an improved appearance. This is one field of longevity which has the potential to be transformative, but of course it is still early days and a lot more studies are needed before we can conclusively determine whether or not young plasma is rejuvenatory.
Young Plasma Rejuvenates Blood Dna Methylation Profile, Extends Mean Lifespan And Improves Physical Appearance In Old Rats Full Text

In this study, a couple of the popular NAD+ precursors were combined with another drug to synergistically extend the lifespan, and improve the physical performance, of fruit flies. Median lifespan extension went from 17% individually to 30% in combination. For us to make any headway in finding effective longevity interventions, we need to discover more of these synergistic combinations.
Dual treatment with kynurenine pathway inhibitors and NAD+ precursors synergistically extends life span in Drosophila Full Text

Great news if you love mushrooms as much as I do - ergothioneine, found mainly in fungi, is shown in this study to improve median male mouse lifespan by 16% and maximum lifespan by 29%, as well as improving physical and mental performance.
Ergothioneine promotes longevity and healthy aging in male mice Full Text

Extra mushroom/ergothioneine studies from March:

Unlocking the Power: New Insights into the Anti-Aging Properties of Mushrooms Full Text

Canadian Content Highlight

In this groundbreaking study, Insilico Medicine, founded by Canadian Alex Zhavoronkov and with one of their sites in Montreal, used AI to generate a target and novel molecule candidate to treat Idiopathic Pulmonary Fibrosis. They reduced the time needed for pre-clinical work from around six years to 18 months! The drug candidate has already passed Phase 1 safety trials and is currently in Phase 2a.

This is not so much about this particular drug, although it also targets several Hallmarks of Aging, it is about the method and its potential to slash the time needed to develop new drugs. As Alex is a long time supporter of longevity, we can be fairly certain that they will also in the future (if not already) use this platform for more specifically longevity focused drugs.
InSilico Shares Details on AI-Generated Drug Candidate Full Text CAN

Supplemental Section

Lifestyle
*Better Life’s Essential 8 contributes to slowing the biological aging process: a cross-sectional study based on NHANES 2007–2010 data Full Text
*Combined effects of sleep and objectively-measured daily physical activity on arterial stiffness in middle-aged and older adults Full Text

Fasting/Dietary Restriction – certainly the cheapest & also one of the most effective anti-ageing interventions currently available. It comes in many flavours, but I fast for at least 12 hours every day.
*Integration of a fasting-mimicking diet programme in primary care for type 2 diabetes reduces the need for medication and improves glycaemic control: a 12-month randomised controlled trial Full Text
*Effect of long-term caloric restriction on telomere length in healthy adults: CALERIE™ 2 trial analysis Full Text
Supplementing probiotics during intermittent fasting proves more effective in restoring ileum and colon tissues in aged rats Full Text

Diet – let food be thy medicine…
*Short-Term Ingestion of Essential Amino Acid Based Nutritional Supplements or Whey Protein Improves the Physical Function of Older Adults Independently of Gut Microbiome Full Text
*Association between dietary inflammatory index and cognitive impairment among American elderly: a cross-sectional study Full Text
*Role of fermented dairy products in the health benefits of a mediterranean diet Full Text

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*Increased frequency of light physical activity during midlife and old age buffers against cognitive declines Full Text
*Daily step count of 9,000 to 10,000 may counteract risk of death and cardiovascular disease in highly sedentary people Full Text
*Do changes in the frailty score differ by the type of group sports and exercises participated in? A 3-year longitudinal study Full Text

Astaxanthin – which is behind the pink colour of salmon & shrimp. Considered the most powerful carotenoid, it has anti-oxidative, anti-inflammatory, anti-cancer, neuro-protective and skin-protective qualities.
The Effects of Astaxanthin on Cognitive Function and Neurodegeneration in Humans: A Critical Review Full Text
Astaxanthin targets IL-6 and alleviates the LPS-induced adverse inflammatory response of macrophages Full Text

Curcumin – the spice which gives curries their yellow colour. Anti-inflammatory and neuroprotective. Needs to be taken with black pepper (piperine) to improve bioavailability.
Curcumin in Cancer and Inflammation: An In-Depth Exploration of Molecular Interactions, Therapeutic Potentials, and the Role in Disease Management Full Text
*A systematic review of the efficacy and safety of turmeric in the treatment of digestive disorders Full Text
Enhancing the Bioavailability and Bioactivity of Curcumin for Disease Prevention and Treatment Full Text

Fisetin
Fisetin alleviates cerebral ischemia/reperfusion injury by regulating Sirt1/Foxc1/Ubqln1 pathway-mediated proteostasis

Nicotinamide MonoNucleotide (NMN)
β-Nicotinamide mononucleotide supplementation prolongs the lifespan of prematurely aged mice and protects colon function in ageing mice Full Text
NAD+ precursor supplementation modulates neurite complexity and survival in motor neurons from ALS models

Nicotinamide Riboside (NR)
The mitochondrial UPR induced by ATF5 attenuates intervertebral disc degeneration via cooperating with mitophagy Full Text
Insulin and glycolysis dependency of cardioprotection by nicotinamide riboside Full Text
The Role and Mechanism of Nicotinamide Riboside in Oxidative Damage and a Fibrosis Model of Trabecular Meshwork Cells Full Text

Resveratrol
Resveratrol Shows Potent Senescence Reversal in Experimental Cellular Models of Particular Matter 2.5-induced Cellular Senescence in Human Dermal Papilla Cells Full Text
Unraveling the therapeutic efficacy of resveratrol in Alzheimer’s disease: an umbrella review of systematic evidence Full Text
Resveratrol as a Promising Nutraceutical: Implications in Gut Microbiota Modulation, Inflammatory Disorders, and Colorectal Cancer Full Text

Spermidine
Spermidine treatment: induction of autophagy but also apoptosis? Full Text

Other available supplements or natural substances (in alphabetical order)
Apigenin: a natural molecule at the intersection of sleep and aging Full Text
*Increased nitrate intake from beetroot juice over 4 weeks affects nitrate metabolism, but not vascular function or blood pressure in older adults with hypertension Full Text
Exploring the anti-atherosclerosis mechanism of ginsenoside Rb1 by integrating network pharmacology and experimental verification Full Text
Targeting the Hallmarks of Aging with Vitamin D: Starting to Decode the Myth Full Text
Kaempferol: Paving the path for advanced treatments in aging-related diseases Full Text
*The duration of lithium use and biological ageing: telomere length, frailty, metabolomic age and all-cause mortality Full Text
*Association of taurine intake with changes in physical fitness among community-dwelling middle-aged and older Japanese adults: an 8-year longitudinal study Full Text
Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia Full Text

Combinations of Supplements
The Combined Antioxidant Effects of N-Acetylcysteine, Vitamin D3, and Glutathione from the Intestinal–Neuronal In Vitro Model Full Text
Cardioprotective effect of antioxidant combination therapy: A highlight on MitoQ plus alpha-lipoic acid beneficial impact on myocardial ischemia-reperfusion injury in aged rats Full Text
*A combination nutritional supplement reduces DNA methylation age only in older adults with a raised epigenetic age Full Text
Mitochondrial transplantation combined with coenzyme Q10 induces cardioprotection and mitochondrial improvement in aged male rats with reperfusion injury Full Text

Prescription Supplements

Rapamycin (sirolimus)
A Low Dose of Rapamycin Promotes Hair Cell Differentiation by Enriching SOX2+ Progenitors in the Neonatal Mouse Inner Ear Organoids
Effects of low-dose rapamycin on lymphoid organs of mice prone and resistant to accelerated senescence Full Text
Rapamycin facilitates the tendon-bone interface healing in an aging rat model of chronic rotator cuff injury

Miscellaneous Molecules & Prescription Drugs
*Can a pill (Ca2+ channel blockade) rescue the vascular endothelium from ageing? Full Text
The protective effects of Irbesartan in cognitive impairment in hypertension Full Text
Sitagliptin elevates plasma and CSF incretin levels following oral administration to nonhuman primates: relevance for neurodegenerative disorders Full Text

Novel Molecules
Tetramethylpyrazine Nitrone alleviates D-galactose-induced murine skeletal muscle aging and motor deficits by activating the AMPK signaling pathway Full Text
A Small Molecule to Restore the Liver Full Text
An Experimental Brain Protector May Fight Obesity Full Text

Other Areas of Interest (in alphabetical order)

Ageing Clocks & other biomarkers of ageing
*Clarifying the biological and statistical assumptions of cross-sectional biological age predictors: an elaborate illustration using synthetic and real data Full Text
*Causal association of obesity with epigenetic aging and telomere length: a bidirectional mendelian randomization study Full Text
Integration of polygenic and gut metagenomic risk prediction for common diseases Full Text

Epigenetics & Cellular Reprogramming
Looking for Safety in Epigenetic Rejuvenation Full Text
Multi-omics characterization of partial chemical reprogramming reveals evidence of cell rejuvenation Full Text
Restoration of neuronal progenitors by partial reprogramming in the aged neurogenic niche

Exosomes (small packets of information released by cells)
BMSCs-derived exosomes inhibit macrophage/microglia pyroptosis by increasing autophagy through the miR-21a-5p/PELI1 axis in spinal cord injury Full Text
Extracellular vesicles from human urine-derived stem cells delay aging through the transfer of PLAU and TIMP1 Full Text
Extracellular vesicles derived from mesenchymal stem cells: the wine in Hebe's hands to treat skin aging Full Text

Genetics including CRISPR
Gene therapy approaches for obesity-induced adipose neuropathy: device-targeted AAV-mediated neurotrophic factor delivery to adipocytes in subcutaneous adipose Full Text
*Novel protective effect of the FOXO3 longevity genotype on mechanisms of cellular aging in Okinawans Full Text
Harnessing Genetics to Extend Lifespan and Healthspan: Current Progress and Future Directions Full Text

Lifespan Lengthening Interventions
Lack of telomerase reduces cancer incidence and increases lifespan of zebrafish tp53M214K mutants Full Text
Queen bee gut microbiota extends honeybee lifespan by inhibiting insulin signaling
Elimination of virus-like particles reduces protein aggregation and extends replicative lifespan in Saccharomyces cerevisiae Full Text

Microbiome
Achieving healthy aging through gut microbiota-directed dietary intervention: Focusing on microbial biomarkers and host mechanisms Full Text
*The Interplay between Gut Microbiota and Cognitive Functioning in the Healthy Aging Population: A Systematic Review Full Text
*The interaction between Mediterranean diet and intestinal microbiome: relevance for preventive strategies against frailty in older individuals Full Text

Observational Studies
*Effects from medications on functional biomarkers of aging in three longitudinal studies of aging in Sweden Full Text
*Association between Body Mass Index and Brain Health in Adults: A 16-Year Population-Based Cohort and Mendelian Randomization Study Full Text
*Sleep duration in midlife and old age and risk of mortality over a 48-year follow-up: The Helsinki businessmen study (HBS) cohort Full Text
*U-shaped association between sleep duration and biological aging: Evidence from the UK Biobank study Full Text

Opinion/Editorials/Theory
Timely Yet Long Overdue: Canadian Standards for Long-Term Care Homes Full Text CAN
National Institute on Aging's 50th anniversary: Advancing aging research and the health and well-being of older adults Full Text
Mother’s Curse effects on lifespan and aging Full Text
AagingBase: a comprehensive database of anti-aging peptides Full Text

Other Ageing Biology
Our cells are less likely to express longer genes as we age, researchers say Full Text
Degeneration via Correcting Progerin Mislocalization Full Text
LPD-3 as a megaprotein brake for aging and insulin-mTOR signaling in C. elegans Full Text

Reproductive Health
Multiple treatments with human embryonic stem cell-derived mesenchymal progenitor cells preserved the fertility and ovarian function of perimenopausal mice undergoing natural aging Full Text
Transplantation of the LRP1high subpopulation of human umbilical cord-derived mesenchymal stem cells improves ovarian function in mice with premature ovarian failure and aged mice Full Text
Research Advances in Stem Cell Therapy for Erectile Dysfunction Full Text

Reviews
CAR T therapy from haematological malignancies to aging-related diseases: An ever-expanding universe Full Text
Vascular Aging and Atherosclerosis: A Perspective on Aging Full Text
A Narrative Review Exploring the Similarities between Cilento and the Already Defined “Blue Zones” in Terms of Environment, Nutrition, and Lifestyle: Can Cilento Be Considered an Undefined “Blue Zone”? Full Text

Senolytics/Senescent Cells
Selective targeting of dipeptidyl-peptidase 4 (DPP-4) positive senescent chondrocyte ameliorates osteoarthritis progression Full Text
Repurposing Drugs for Senotherapeutic Effect: Potential Senomorphic Effects of Female Synthetic Hormones Full Text
Natural Senotherapeutics that Mimic Dasatinib Full Text
An in vivo screening platform identifies senolytic compounds that target p16INK4a+ fibroblasts in lung fibrosis Full Text

Skin & Beauty
*Efficacy and Safety of Skin Radiance Collagen on Skin and Hair Matrix: A Placebo-Controlled Clinical Trial in Healthy Human Subjects Full Text
*Oral consumption of Bonito fish-derived elastin peptide (VGPG Elastin®) improves biophysical properties in aging skin: A randomized, double-blinded, placebo-controlled study Full Text
The Potential of Exercise on Lifestyle and Skin Function: Narrative Review Full Text

Stem Cells
Restoring Lymphoid-Myeloid Balance Boosts Immunity in Mice Abstract
The Rejuvenation and Functional Restoration of Aged Adipose Stem Cells by DUXAP10 Knockdown via the Regulation of the miR-214-3p/RASSF5 Axis Full Text
Osteopontin Rejuvenates Senescent Adipose-Derived Stem Cells and Restores their Bone Tissue Regenerative Function Full Text
Mesenchymal stem cells reverse thymus aging by reprogramming the DNA methylation of thymic epithelial cells Full Text

Telomeres
*Efficacy of a dietary supplement derived from five edible plants on telomere length in Thai adults: A randomized, double-blind, placebo-controlled trial Full Text
*Exploring the interplay of psychological and biological components of stress response and telomere length in the transition from middle age to late adulthood: A systematic review Full Text
*Aging Processes Are Affected by Energy Balance: Focused on the Effects of Nutrition and Physical Activity on Telomere Length Full Text

Chris Linnell's Longevity Review Newsletter - February 2024 Longevity Review 24 March 2024 - 01:18 PM

As we get past the heart of winter, this month we will take a look at how partial reprogramming extends the remaining lifespan of old naturally aged mice; how the Fasting Mimicking Diet reduces biological age; a comparison of intermittent versus continuous dosing of rapamycin in mice; and, a human senolytic trial which raises some concerning questions.

In the supplemental section, you will find additional studies on protein sources and their effect on ageing; a reanalysis of an NMN human trial showing a dose response; the combination of choline and B12 on cognitive impairment; a systematic review of rapamycin in humans for ageing; young plasma for chronic kidney disease progression; modulating the gut microbiome to improve cognitive function; and a link between spirituality and longevity. Plus of course much more!

Canadian Longevity Association News

We had our first board meeting in February, which marks an important milestone in becoming a more professional organization. The CLA also attended a Life Sciences Ontario networking event and visited Dr Karim Mekail, who is doing some amazing longevity research at the U of T, and who has agreed to join our nascent scientific advisory board.

Donate to the Canadian Longevity Association

Please also follow, or join us on social media:

Twitter/X (I also have a personal account with more frequent longevity updates)

Facebook Instagram LinkedIn Meetup

Canadian Longevity Association YouTube Channel - where you can find video talk-throughs of these reviews.

Discord for longevity related chats and the place to have all your longevity related questions answered.

February 2024 Round-Up:

Partial reprogramming is one of the hot areas in longevity research and shows great potential. But, until now we haven’t known what lifespan effects it has in normal aged mice. This study puts an end to that by showing that when given to mice at the equivalent human age of 77, it increased remaining lifespan by 109%.
Gene Therapy-Mediated Partial Reprogramming Extends Lifespan and Reverses Age-Related Changes in Aged Mice Full Text

Fasting has many beneficial effects, especially if it can be done over multiple days, yet it is hard to accomplish. The Fasting Mimicking Diet (FMD) seeks to make it easier by providing a minimal amount of food and reduced protein over five days while maintaining the benefits. In this latest study, it reduced participants' median biological age by 2.5 years.
*Fasting-Mimicking Diet Might Extend Lifespan in Humans Full Text

There is no longer any question that rapamycin can extend health and lifespan (in mice at least!), but what treatment regime should be used is still up for question. This study, once again in mice, compares the sex specific effects between continuous and intermittent dosing. Continuous dosing overall had greater benefits, but one week on/off kept a lot of those benefits while reducing some side effects.
Intermittent Rapamycin Lessens Negative Effects in Mice Full Text

Finally another senolytic clinical has released its results using Dasatinib & Quercetin in the first part, before Fisetin was added to the mix in the second half. The study sought to see how various epigenetic clocks responded to these senolytics, and it turned out to be a bit of a mixed bag, with there being some age acceleration with some of the clocks.
*Exploring the effects of Dasatinib, Quercetin, and Fisetin on DNA methylation clocks: a longitudinal study on senolytic interventions Full Text

Supplemental Section

Fasting/Dietary Restriction – certainly the cheapest & also one of the most effective anti-ageing interventions currently available. It comes in many flavours, but I fast for at least 12 hours every day.
*Effectiveness of an intermittent fasting diet versus regular diet on fat loss in overweight and obese middle-aged and olderly people without metabolic disease: a systematic review and meta-analysis of randomized controlled trials Full Text
Short-term periodic restricted feeding elicits metabolome-microbiome signatures with sex dimorphic persistence in primate intervention Full Text
Short-term fasting of a single amino acid extends lifespan Full Text

Diet – let food be thy medicine…
Eating too much protein is bad for your arteries, and this amino acid is to blame Abstract
*Empirically derived dietary patterns are associated with major adverse cardiovascular events, all-cause mortality, and congestive cardiac failure in older men: The Concord Health and Ageing in Men Project Full Text
*The MIND diet for the ageing brain: a systematic review Full Text
*Dietary protein intake in midlife in relation to healthy aging – results from the prospective Nurses’ Health Study cohort Full Text

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*High-intensity acute exercise impacts motor learning in healthy older adults Full Text
*Enhanced memory and hippocampal connectivity in humans 2 days after brief resistance exercise Full Text
*The intensity paradox: A systematic review and meta-analysis of its impact on the cardiorespiratory fitness of older adults Full Text
*Sedentary behavior increases mortality risk Full Text

Fisetin
Fisetin orchestrates neuroinflammation resolution and facilitates spinal cord injury recovery through enhanced autophagy in pro-inflammatory glial cells

Melatonin
*The Effect of Melatonin Supplement on High Arterial Blood Pressure: An Overview from Clinicaltrials.gov Full Text
Systematic review of melatonin in cerebral ischemia-reperfusion injury: critical role and therapeutic opportunities Full Text
*The Effect of Melatonin Supplementation on Cancer-Related Fatigue during Chemotherapy Treatment of Breast Cancer Patients: A Double-Blind, Randomized Controlled Study Full Text

Nicotinamide MonoNucleotide (NMN)
*Towards personalized nicotinamide mononucleotide (NMN) supplementation: Nicotinamide adenine dinucleotide (NAD) concentration Full Text
β-Nicotinamide Mononucleotide Promotes Cell Proliferation and Hair Growth by Reducing Oxidative Stress Full Text
Glycolysis-Mediated Activation of v-ATPase by Nicotinamide Mononucleotide Ameliorates Lipid-Induced Cardiomyopathy by Repressing the CD36-TLR4 Axis Full Text

Nicotinamide Riboside (NR)
Comparison of protective effects of nicotinamide mononucleotide and nicotinamide riboside on DNA damage induced by cisplatin in HeLa cells Full Text
Nicotinamide Riboside Regulates Chemotaxis to Decrease Inflammation and Ameliorate Functional Recovery Following Spinal Cord Injury in Mice Full Text

Pterostilbene
Design, synthesis, in vitro and in vivo biological evaluation of pterostilbene derivatives for anti-inflammation therapy Full Text

Resveratrol
Resveratrol prevents age-related heart impairment through inhibiting the Notch/NF-κB pathway Full Text
A novel model of sensorineural hearing loss induced by repeated exposure to moderate noise in mice: the preventive effect of resveratrol Full Text
*Effects of resveratrol on the anthropometric indices and inflammatory markers: an umbrella meta-analysis

Spermidine
Spermidine ameliorates osteoarthritis via altering macrophage polarization
Synergistic effect of spermidine and ciprofloxacin against Alzheimer's disease in male rat via ferroptosis modulation

Other available supplements or natural substances (in alphabetical order)
Caffeine Ameliorates Age-Related Hearing Loss by Downregulating the Inflammatory Pathway in Mice Full Text
Glycine supplementation can partially restore oxidative stress associated glutathione deficiency in ageing cats
Effects of Ferulic Acid on Cognitive Function: A Systematic Review Full Text
Magnesium and the Hallmarks of Aging Full Text
*An analysis of omega-3 clinical trials and a call for personalized supplementation for dementia prevention Full Text

Combinations of Supplements
*Combining Choline Bitartrate and Vitamin B12 Ameliorates Cognitive Impairment in Hypertensive Elders with Cognitive Frailty Full Text
The Potential Use of Vitamin D3 and Phytochemicals for Their Anti-Ageing Effects Full Text

Prescription Supplements

Metformin
Examining the clinical relevance of metformin as an antioxidant intervention Full Text

Rapamycin (sirolimus)
The Latest in Rapamycin Research on Humans Full Text
Activating autophagy promotes skin regeneration induced by mechanical stretch during tissue expansion Full Text
Rapamycin rescues loss-of-function in blood-brain barrier-interacting regulatory T cells Full Text

Miscellaneous Molecules & Prescription Drugs
Minocycline alleviates LPS-induced cognitive dysfunction in mice by inhibiting the NLRP3/caspase-1 pathway Full Text

Novel Molecules
COP-22 Alleviates D-Galactose–Induced Brain Aging by Attenuating Oxidative Stress, Inflammation, and Apoptosis in Mice Full Text

Other Areas of Interest (in alphabetical order)

Ageing Clocks & other biomarkers of ageing
*Epigenetic Clocks Help Predict Health Outcomes Full Text
Aging clock based on nucleosome reorganisation derived from cell-free DNA Full Text
Genome-wide transcriptome profiling and development of age prediction models in the human brain Full Text

Blood Factors or other Heterochronic Transplantation
Young Plasma Attenuated Chronic Kidney Disease Progression after Acute Kidney Injury by Inhibiting Inflammation in Mice Full Text

Epigenetics & Cellular Reprogramming
Cell Reprogramming Strategies for Treating Osteoarthritis and Intervertebral Disc Degeneration Full Text
Cellular reprogramming as a tool to model human aging in a dish Full Text

Exosomes (small packets of information released by cells)
Myogenic exosome miR-140-5p modulates skeletal muscle regeneration and injury repair by regulating muscle satellite cells Full Text
Extracellular vesicles from UTX-knockout endothelial cells boost neural stem cell differentiation in spinal cord injury Full Text

Genetics including CRISPR
Therapeutic potential of AAV-FL-Klotho in obesity: Impact on weight loss and lipid metabolism in mice

Lifespan Lengthening Interventions
Restricting bioenergetic efficiency enhances longevity and mitochondrial redox capacity in Drosophila melanogaster Full Text
Betulinic Acid Increases the Lifespan of Drosophila melanogaster via Sir2 and FoxO Activation Full Text
Endogenous chondroitin extends the lifespan and healthspan in C. elegans Full Text

Microbiome
*Probiotics supplementation or probiotic-fortified products on sarcopenic indices in older adults: systematic review and meta-analysis from recent randomized controlled trials Full Text
*Alterations of the gut microbiome are associated with epigenetic age acceleration and physical fitness Full Text
*Effect of gut microbiome modulation on muscle function and cognition: the PROMOTe randomised controlled trial Full Text
*Association of dietary live microbe intake with frailty in US adults: evidence from NHANES Full Text

Observational Studies
*Higher Abdominal Fat Associated with Cognitive Decline Full Text
*Consequences of heterogeneity in aging: parental age at death predicts midlife all-cause mortality and hospitalization in a Swedish national birth cohort Full Text
*Comparison of three frailty measures for predicting hospitalization and mortality in the Canadian Longitudinal Study on Aging Full Text CAN

Opinion/Editorials/Theory
Why death and aging ? All memories are imperfect
Is Aging a Disease? A Critical Review Within the Framework of Ageism Full Text
A unified framework for evolutionary genetic and physiological theories of aging Full Text

Other Ageing Biology
Pharmacological interventions in human aging database
Restoration of norepinephrine release, cognitive performance, and dendritic spines by amphetamine in aged rat brain Full Text
Age-, sex- and proximal–distal-resolved multi-omics identifies regulators of intestinal aging in non-human primates Full Text
PandaOmics: An AI-Driven Platform for Therapeutic Target and Biomarker Discovery Full Text CAN

Reproductive Health
The Antioxidant Salidroside Ameliorates the Quality of Postovulatory Aged Oocyte and Embryo Development in Mice Full Text
Cellular senescence in the pathogenesis of ovarian dysfunction Full Text
Senolytic treatment fails to improve ovarian reserve or fertility in female mice
New insights into ginsenoside Rg1 regulating the niche to inhibit age-induced germline stem cells depletion through targeting ECR/BMP signaling pathway in Drosophila Full Text

Reviews
The therapeutic perspective of NAD+ precursors in age-related diseases Full Text
The interplay between obesity, immunosenescence, and insulin resistance Full Text
The salamander limb: a perfect model to understand imperfect integration during skeletal regeneration Full Text

Senolytics/Senescent Cells
MicroRNA-146a gene transfer ameliorates senescence and senescence-associated secretory phenotypes in tendinopathic tenocytes Full Text
Cellular senescence: Neither irreversible nor reversible Full Text
Senolytics: from pharmacological inhibitors to immunotherapies, a promising future for patients’ treatment Full Text

Skin & Beauty
*Polynucleotides HPT for Asian Skin Regeneration and Rejuvenation Full Text
Dietary Isoeugenol Supplementation Attenuates Chronic UVB-Induced Skin Photoaging and Modulates Gut Microbiota in Mice Full Text
*Evaluation of an advanced antioxidant and double-conjugated retinoid/AHA cream in participants with FST IV–V Full Text

Stem Cells
MiR-145-5p overexpression rejuvenates aged adipose stem cells and accelerates wound healing Full Text
Mesenchymal Stem Cell Transplantation Has a Regenerative Effect in Ischemic Myocardium: An Experimental Rat Model Evaluated by SPECT-CT Assessment Full Text
MSX1+PDGFRAlow limb mesenchyme-like cells as an efficient stem cell source for human cartilage regeneration Full Text

Telomeres
*Association between modifiable lifestyle factors and telomere length: a univariable and multivariable Mendelian randomization study Full Text

Odds & Sods
Cumulative Deleterious Effects of Tetrahydrocannabinoid (THC) and Ethanol on Mitochondrial Respiration and Reactive Oxygen Species Production Are Enhanced in Old Isolated Cardiac Mitochondria Full Text
Enriched oxygen improves age-related cognitive impairment through enhancing autophagy Full Text
The link between spirituality and longevity Full Text
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***Disclaimer 1 – I am NOT a doctor or indeed a scientist. All the information pertained within is for information purposes only; use at your own risk. Please consult with a healthcare practitioner if you need medical advice.***

Chris Linnell's Longevity Review Newsletter - January 2024 Longevity Review 27 February 2024 - 12:04 AM

Kicking off the new year with a bevy of interesting longevity research including the intriguing possibility of lifelong protection against senescent cells, harnessing the immune system’s pathogen response to treat ageing, using rapamycin to encourage hair growth, and, in a new addition focusing on Canadian researchers working on longevity, a novel compound which shows potential to rapidly reverse certain aspects of ageing.

In the supplemental section you will find a scoping review of intermittent fasting, a study making me reconsider my aversion to taking a multivitamin, how brain to fat tissue communication increases mouse lifespan, and three general reviews of anti-ageing interventions, plus of course much more!

In addition, and in light of a greater focus on Canadian longevity research (we are the CLA after all), any Canadian research making the grade of this newsletter will be denoted by a CAN after the link.

And in a little bit of housekeeping news, I’ve made a few changes to how these newsletters and videos are put together, including finally getting a video editor instead of relying on YouTube’s inbuilt version (I know, I know!), so that they are easier to produce and should come out in a more timely manner henceforth.

Donate to the Canadian Longevity Association

Canadian Longevity Association Website

Please also follow, or join us on social media so that we can grow our reach:

Twitter/X (I also have a personal account with more frequent longevity updates)

Facebook Instagram LinkedIn Meetup

Canadian Longevity Association YouTube Channel - where you can find video talk-throughs of these reviews.

Discord for longevity related chats and the place to have all your longevity related questions answered.

January 2024 Highlights:

This paper is not the first time that CAR T cells, which have been successfully deployed against blood cancers, have been repurposed to clear senescent cells from a mouse. However, this is the first time that they have shown the same persistence as seen in cancer, leading to the possibility of a “once and done” treatment for senescent cells. This treatment also prevented mice from developing metabolic syndrome on a high fat diet.
The fountain of youth is ... a T cell? CAR T Therapy Lowers Senescence, Improves Health in Mice Lifespan,io Reveiw Full Text

Researchers in this paper discovered that activating an immune system receptor led to life extension in mice ( and improvement in various physiological parameters. A quite impressive result which brings up the possibility of modulating the immune system to improve longevity.
Mucosal TLR5 activation controls healthspan and longevity Full Text

Although primarily concerned with basic biology, this paper is sure to interest those who are, shall we say, “follically challenged”, as it shows that not only is autophagy needed for hair growth in mice, but that rapamycin, as an autophagy activator, greatly encourages it. This seems very readily translatable to humans.
Rapamycin Rescues Hair Growth in Mice Full Text

Canadian Research Highlight - longevity research involving Canadian researchers, wholly or in part:

An in silico screen of molecules against a genetic longevity database brought up a novel compound which showed potential for reversing certain aspects of ageing in the kidney, brain and hearts of mice. With contributions from the University of Ottawa researchers.
HDAC1/2 inhibitor therapy improves multiple organ systems in aged mice Full Text

Supplemental Section

Lifestyle
*The combination of physical activity with fruit and vegetable intake associated with life satisfaction among middle-aged and older adults: a 16-year population-based cohort study Full Text
*Life’s Essential 8 in relation to self-rated health and health-related quality of life in a large population-based sample: the SCAPIS project Full Text
*Effectiveness of a combined lifestyle intervention for older people in long-term care: A randomized controlled trial Full Text

Fasting/Dietary Restriction – certainly the cheapest & also one of the most effective anti-ageing interventions currently available. It comes in many flavours, but I fast for at least 12 hours every day.
*What Time-Restricted Eating Does and Doesn’t Affect Full Text
*Impact of Intermittent Fasting and/or Caloric Restriction on Aging-Related Outcomes in Adults: A Scoping Review of Randomized Controlled Trials Full Text
*Effect of Calorie Restriction and Intermittent Fasting Regimens on Brain-Derived Neurotrophic Factor Levels and Cognitive Function in Humans: A Systematic Review Full Text

Diet – let food be thy medicine…
*High Tyrosol and Hydroxytyrosol Intake Reduces Arterial Inflammation and Atherosclerotic Lesion Microcalcification in Healthy Older Populations Full Text CAN
*Composite dietary antioxidant index associated with delayed biological aging: a population-based study Full Text
*Metabolome biomarkers linking dietary fibre intake with cardiometabolic effects: results from the Danish Diet, Cancer and Health-Next Generations MAX study Full Text

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*How Cardiovascular Mortality Goes Down with Exercise Full Text
*New research finds half-cardio, half-strength training reduces cardiovascular disease risks Full Text
*High‐Intensity Interval Training Is Associated With Improved 10‐Year Survival by Mediating Left Ventricular Remodeling in Patients With Heart Failure With Reduced and Mid‐Range Ejection Fraction Full Text

Astaxanthin – which is behind the pink colour of salmon & shrimp. Considered the most powerful carotenoid, it has anti-oxidative, anti-inflammatory, anti-cancer, neuro-protective and skin-protective qualities.
*Effects of Astaxanthin Supplementation on Fatigue, Motor Function and Cognition: A Meta-Analysis of Randomized Controlled Trials
Astaxanthin Alleviates the Process of Cardiac Hypertrophy by Targeting the METTL3/Circ_0078450/MiR-338-3p/GATA4 Pathway Full Text
PEGylated-liposomal astaxanthin ameliorates Aβ neurotoxicity and Alzheimer-related phenotypes by scavenging formaldehyde Full Text

Curcumin – the spice which gives curries their yellow colour. Anti-inflammatory and neuroprotective. Needs to be taken with black pepper (piperine) to improve bioavailability.
*Curcumin effects on glycaemic indices, lipid profile, blood pressure, inflammatory markers and anthropometric measurements of non-alcoholic fatty liver disease patients: A systematic review and meta-analysis of randomized clinical trials Full Text
*Curcumin supplementation effect on liver enzymes in patients with nonalcoholic fatty liver disease: a GRADE-assessed systematic review and dose–response meta-analysis of randomized controlled trials
*Nanocurcumin supplementation improves pulmonary function in severe COPD patients: A randomized, double blind, and placebo-controlled clinical trial

Fisetin
Fisetin suppresses chondrocyte senescence and attenuates osteoarthritis progression by targeting sirtuin 6

Melatonin
Mitochondrial Melatonin: Beneficial Effects in Protecting against Heart Failure Full Text
The potential influence of melatonin on mitochondrial quality control: a review Full Text
Comprehensive review of melatonin as a promising nutritional and nutraceutical supplement Full Text

Nicotinamide MonoNucleotide (NMN)
*Safety and efficacy of long-term nicotinamide mononucleotide supplementation on metabolism, sleep, and nicotinamide adenine dinucleotide biosynthesis in healthy, middle-aged Japanese men Full Text
NAD+ supplementation prevents STING-induced senescence in CD8+ T cells by improving mitochondrial homeostasis
NAD+ dependent UPRmt activation underlies intestinal aging caused by mitochondrial DNA mutations Full Text

Nicotinamide Riboside (NR)
NAD+ Precursors Reverse Experimental Diabetic Neuropathy in Mice Full Text

Pterostilbene
Pterostilbene in the treatment of inflammatory and oncological diseases Full Text

Resveratrol
Resveratrol attenuates advanced glycation end product-induced senescence and inflammation in human gingival fibroblasts Full Text
Unveiling the potential effects of resveratrol in lung cancer treatment: Mechanisms and nanoparticle-based drug delivery strategies Full Text

Other available supplements & natural substances (in alphabetical order)
α-Ketoglutarate improves cardiac insufficiency through NAD+-SIRT1 signaling-mediated mitophagy and ferroptosis in pressure overload-induced mice Full Text
Relationship of Low Vitamin B6 Status with Sarcopenia, Frailty, and Mortality: A Narrative Review Full Text
*Effect of the ketone beta-hydroxybutyrate on markers of inflammation and immune function in adults with type 2 diabetes
*Vitamin D3 inhibits p38 MAPK and senescence-associated inflammatory mediator secretion by senescent fibroblasts that impacts immune responses during ageing Full Text
*The associations of serum vitamin D status and vitamin D supplements use with all-cause dementia, Alzheimer’s disease, and vascular dementia: a UK Biobank based prospective cohort study Full Text
Therapeutic applications of ginseng for skeletal muscle-related disorder management Full Text
Red Ginseng Attenuates the Hepatic Cellular Senescence in Aged Mice Full Text
Hydrogen Water: Extra Healthy or a Hoax?—A Systematic Review Full Text
Exploring the Neuroprotective Effects of Lithium in Ischemic Stroke: A literature review Full Text
*Effect of Nigella sativa Consumption on Lipid Profile and Glycemic Index in Patients with Metabolic Syndrome: A Systematic Review and Meta-analysis of Randomized Controlled Trials
*Cuban policosanol improves high-density lipoprotein cholesterol efflux capacity in healthy Japanese subjects Full Text
Mitophagy curtails cytosolic mtDNA-dependent activation of cGAS/STING inflammation during aging Full Text urolithin A

Combinations of Supplements
*Third major study finds evidence that daily multivitamin supplements improve memory and slow cognitive aging in older adults Abstract
Combination of phytochemicals, including ginsenoside and curcumin, shows a synergistic effect on the recovery of radiation-induced toxicity Full Text
*Combined Turmeric, Vitamin C, and Vitamin D Ready-to-Drink Supplements Reduce Upper Respiratory Illness Symptoms and Gastrointestinal Discomfort in Elite Male Football Players Full Text

Prescription Supplements

Metformin
*Incident dementia risk among patients with type 2 diabetes receiving metformin versus alternative oral glucose-lowering therapy: an observational cohort study using UK primary healthcare records Full Text
*Association of metformin use and cancer incidence: a systematic review and meta-analysis
*Effect of metformin and lifestyle intervention on adipokines and hormones in breast cancer survivors: a pooled analysis from two randomized controlled trials Full Text

Rapamycin (sirolimus)
Rapamycin mitigates inflammation-mediated disc matrix homeostatic imbalance by inhibiting mTORC1 and inducing autophagy through Akt activation Full Text
Rapamycin Alleviates Neuronal Injury and Modulates Microglial Activation After Cerebral Ischemia
Mitophagy Activation by Rapamycin Enhances Mitochondrial Function and Cognition in 5×FAD Mice Full Text

Miscellaneous Molecules & Prescription Drugs
*Cholinesterase inhibitors are associated with reduced mortality in patients with Alzheimer's disease and previous myocardial infarction Full Text
*Effects of SGLT2 Inhibition via Empagliflozin on Cognitive and Physical Impairment in Frail Diabetic Elders with Chronic Kidney Disease Full Text
*(SGLT2) in frail or older people with type 2 diabetes and heart failure: a systematic review and meta-analysis Full Text

Other Areas of Interest (in alphabetical order)

Ageing Clocks & other biomarkers of ageing
*Prognostic accuracy of 70 individual frailty biomarkers in predicting mortality in the Canadian Longitudinal Study on Aging Full Text CAN
Epigenetic drift underlies epigenetic clock signals, but displays distinct responses to lifespan interventions, development, and cellular dedifferentiation Full Text
*Body size, diet quality, and epigenetic ageing: cross-sectional and longitudinal analyses Full Text

Epigenetics & Cellular Reprogramming
Epigenetic Reprogramming as a Key to Reverse Ageing and Increase Longevity Full Text
Epigenetic Reprogramming to Repair Genetic Damage Full Text

Exosomes (small packets of information released by cells)
Exosomes in skin photoaging: biological functions and therapeutic opportunity Full Text
*Acute exercise-induced release of innate immune proteins via small extracellular vesicles changes with aerobic fitness and age Full Text

Genetics including CRISPR
*Alzheimer’s Disease and Aging Association: Identification and Validation of Related Genes
*Investigation of genetic determinants of cognitive change in later life Full Text
Longevity-CancerDB: unlocking the distinctive features and roles of longevity-associated genes in tumourigenesis Full Text

Lifespan Lengthening Interventions
Improved Brain-Fat Communication Extends Lifespan in Mice Full Text
GV1001 reduces neurodegeneration and prolongs lifespan in 3xTg-AD mouse model through anti-aging effects Full Text
Longevity interventions modulate mechanotransduction and extracellular matrix homeostasis in C. elegans Full Text
PICLS with human cells is the first high throughput screening method for identifying novel compounds that extend lifespan Full Text

Microbiome
A gut aging clock using microbiome multi-view profiles is associated with health and frail risk Full Text
Potential of dietary polyphenols for protection from age-related decline and neurodegeneration: a role for gut microbiota? Full Text
Identification of Muscle Strength-Related Gut Microbes through Human Fecal Microbiome Transplantation Full Text

Observational Studies
*Impact of sleep duration and sleep disturbances on the incidence of dementia and Alzheimer's disease: A 10-year follow-up study Full Text
*The Influence of Metabolic Syndrome on Potential Aging Biomarkers in Participants with Metabolic Syndrome Compared to Healthy Controls Full Text
*Implications of metabolism on multi-systems healthy aging across the lifespan Full Text

Opinion/Editorials/Theory
Should the European Medicines Agency consider ageing a disease? Full Text
Growing old while staying young: The unique mechanisms that defy aging in plants Full Text
Seven knowledge gaps in modern biogerontology Full Text
The Gompertz Law emerges naturally from the inter-dependencies between sub-components in complex organisms Full Text
The hallmarks of aging as a conceptual framework for health and longevity research Full Text

Other Ageing Biology
The unfolded protein response of the endoplasmic reticulum protects Caenorhabditis elegans against DNA damage caused by stalled replication forks Full Text CAN
Fibroblast growth factor 21 alleviates diabetes-induced cognitive decline Full Text
Intermittent cytomegalovirus infection alters neurobiological metabolism and induces cognitive deficits in mice Full Text

Regenerative Medicine
Hydrogel-Based Strategies for Intervertebral Disc Regeneration: Advances, Challenges and Clinical Prospects Full Text
Dual delivery gene-activated scaffold directs fibroblast activity and keratinocyte epithelization Full Text

Reproductive Health
The influence of the gut microbiome on ovarian aging Full Text
Human Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes Rescue Testicular Aging Full Text
*Muscle Strength and Male Sexual Function Full Text
Cellular and molecular mechanisms of highly active mesenchymal stem cells in the treatment of senescence of rhesus monkey ovary Full Text
Chitosan Treatment Reduces Ovarian Senescence in Mice Full Text

Reviews
Anti-Aging Drugs and the Related Signal Pathways Full Text
Antiaging Strategies and Remedies: A Landscape of Research Progress and Promise Full Text
Eternal Youth: A Comprehensive Exploration of Gene, Cellular, and Pharmacological Anti-Aging Strategies Full Text

Senolytics/Senescent Cells
Researching New Drug Combinations with Senolytic Activity Using Senescent Human Lung Fibroblasts MRC-5 Cell Line Full Text
Senolytic treatment alleviates doxorubicin-induced chemobrain Full Text

Skin & Beauty
*A proof of concept: Clinical anti-aging efficacy and safety of Lactiplantibacillus plantarum LB244R® applied topically in a double-blinded placebo-controlled study Full Text
*Skin rejuvenation and photoaging protection using adipose-derived stem cell extracellular vesicles loaded with exogenous cargos Full Text
*Beverage consumption and facial skin aging: Evidence from Mendelian randomization analysis Full Text

Telomeres
*Effects of Physical Exercise on Telomere Length in Healthy Adults: Systematic Review, Meta-Analysis, and Meta-Regression Full Text
*The Relationship between Dietary Macronutrient Composition and Telomere Length Among US Adults Full Text

Odds & Sods
Fighting with Aging: The Secret for Keeping Health and Longevity of Naked Mole Rats Full Text
*How aging shapes our sense of agency Full Text
*Social network type contributes to purpose in life among older people, mediated by social support Full Text
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***Disclaimer 1 – I am NOT a doctor or indeed a scientist. All the information pertained within is for information purposes only; use at your own risk. Please consult with a healthcare practitioner if you need medical advice.***

Chris Linnell's Longevity Review Newsletter - November 2023 Longevity Review 26 February 2024 - 10:57 PM

This review was a few sentences and an intro away from being finished a few weeks ago before the drama of needing to get a last minute passport derailed my ambitions. I also then used the festive period visiting family in Germany to do a social media/digital/longevity detox for the first time in a number of years. Mea culpa aside, this month’s review is bristling with actionable studies, especially in the diet and exercise sections, which have been expanded to help your motivation for those New Year's resolutions!

In addition, I saw so many studies on sleep and the longevity molecule klotho this month that they both got their own mini-section. Among the other highlights of the supplemental section include using electricity to combat skin senescence, the benefits adding astaxanthin or coffee to exercise, a review of berberine for diabetes and resveratrol for muscle insulin resistance, and the first time I’ve seen a clinical trial brown seaweed for maintaining muscle strength in older humans.

And finally, worth checking out in the opinions section is a novel hypothesis for the ageing of mammals - blame the dinosaurs! Plus of course much more...

Canadian Longevity Association Website

Please also follow or join us on social media so that we can grow our reach:

Twitter/X (I also have a personal account with more frequent longevity updates)

Facebook Instagram LinkedIn Meetup

Discord for longevity related chats and the place to have all your longevity related questions answered.

Donate to the Canadian Longevity Association

December 2023 Round-Up:

In this intriguing study, researchers used mechanical means to partially reprogram and rejuvenate aged skin cells (75 year old donor), and when implanted into an in vitro human full thickness aged skin model, improved it by increasing production of collagen, elastin and fibronectin - the last two even more than young cells. In addition, the cells also facilitated better wound closure. This mechanical method of reprogramming could be a means of circumventing some of the issues found with current methods.
Mechanically Reprogrammed Fibroblasts for Skin Rejuvenation Full Text

In this study, researchers found a subset of bone marrow derived cells which could help rejuvenate aged blood vessels, and that a substance, pamidronate (PAM), could achieve the same results. Not only that, but PAM also extended the lifespan of both progeroid and naturally aged mice, though the numbers used in the experiments were very small.
CD133+ endothelial-like stem cells restore neovascularization and promote longevity in progeroid and naturally aged mice Full Text

The authors of this study propose and find evidence that there exists a class of cells which fall between normal functioning young and senescent old cells, which they term “Mid-old cells”. These mid-old cells have upregulated pro-inflammatory genes and downregulated anti-inflammatory genes, as well as a general decline in function. They also found that an anti-inflammatory cytokine, SLIT2, which is secreted by young cells, could reverse this, and when injected into old mice, increased muscle mass and how far they could run.
Pre-Senescent Cells May Be Damaging and Treatable Full Text

Originally behind a paywall, this review of longevity related rapamycin clinical trials is now available to all. There are ten trials either ongoing or due to start soon, including the PEARL trial which I helped with the crowdfunding. They should hopefully give us an indication of whether the substantial benefits seen in humans translate to humans.
*Blazing a trail for the clinical use of rapamycin as a geroprotecTOR Full Text (October 2023)

Supplemental Section

Lifestyle
Lifestyle Interventions Against Cellular Senescence Full Text
*Comprehensive lifestyle modification interventions for metabolic syndrome: A systematic review and meta-analysis Full Text

Fasting/Dietary Restriction – certainly the cheapest & also one of the most effective anti-ageing interventions currently available. It comes in many flavours, but I fast for at least 12 hours every day.
*Caloric Restriction Associated With Reduced Senescence Full Text
Aging Might Blunt the Effects of Fasting Full Text
Mechanisms underlying retardation of aging by dietary energy restriction Full Text

Diet – let food be thy medicine…
*New research links high salt consumption to risk of Type 2 diabetes Full Text
*Effect of Dietary Sodium on Blood Pressure Full Text
*Plant-Based Alternatives Are Associated With Less Disease Full Text
*Twin Study: Healthy Vegan Diet Beats Healthy Omnivorous Diet Full Text
*Healthy Diet Linked to Massive Gains in Life Expectancy Full Text

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*Effects of exercise interventions on cognitive functions in healthy populations: A systematic review and meta-analysis Full Text
*Efficacy of morning versus afternoon aerobic exercise training on reducing metabolic syndrome components: A randomized controlled trial Full Text
*Dose-response of accelerometer-measured physical activity, step count, and cancer risk in the UK Biobank: a prospective cohort analysis
*Effect of physical activity on risk of Alzheimer's disease: a systematic review and meta-analysis of twenty-nine prospective cohort studies
*Running Is Associated With Better Health Biomarkers Full Text
*The effect of regular running on body weight and fat tissue of individuals aged 18 to 65 Full Text

Curcumin – the spice which gives curries their yellow colour. Anti-inflammatory and neuroprotective. Needs to be taken with black pepper (piperine) to improve bioavailability.
*Nano-curcumin effects on nicotine dependence, depression, anxiety and metabolic parameters in smokers: A randomized double-blind clinical study Full Text
*The effect of curcumin supplementation on circulating adiponectin and leptin concentration in adults: A GRADE-assessed systematic review and meta-analysis of randomized controlled trials
*Effects of curcumin/turmeric supplementation on the liver enzymes, lipid profiles, glycemic index, and anthropometric indices in non-alcoholic fatty liver patients: An umbrella meta-analysis

Fisetin
Role of Fisetin in Selected Malignant Neoplasms in Women Full Text
Exploring the therapeutic potential of fisetin: a comprehensive study on its anti-nociceptive and anti-inflammatory effects Full Text
Exploring the underlying mechanisms of fisetin in the treatment of hepatic insulin resistance via network pharmacology and in vitro validation Full Text

Melatonin
*Melatonin supplementation enhances pulmonary rehabilitation outcomes in COPD: A randomized, double-blind, placebo-controlled study

Nicotinamide MonoNucleotide (NMN)
Tumor cell-induced macrophage senescence plays a pivotal role in tumor initiation followed by stable growth in immunocompetent condition Full Text (NMN potentially protective against cancer)
Nicotinamide mononucleotide pretreatment improves long-term isoflurane anesthesia-induced cognitive impairment in mice Full Text

Nicotinamide Riboside (NR)
*A randomized placebo-controlled trial of nicotinamide riboside in older adults with mild cognitive impairment
*NR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson’s disease Full Text

Pterostilbene
Unlocking the therapeutic potential of natural stilbene: Exploring pterostilbene as a powerful ally against aging and cognitive decline

Resveratrol
Resveratrol improves the prognosis of rats after spinal cord injury by inhibiting mitogen-activated protein kinases signaling pathway Full Text
Resveratrol and Its Derivatives in Inflammatory Skin Disorders—Atopic Dermatitis and Psoriasis: A Review Full Text
Resveratrol as a potential protective compound against skeletal muscle insulin resistance Full Text*

Spermidine
*Dietary polyamine intake and all-cause and cause-specific mortality in Japanese adults in the Takayama study Full Text

Other available supplements (in alphabetical order)
Addressing the preventive and therapeutic perspective of berberine against diabetes Full Text
Effect of vitamin D on cardiac hypertrophy in D-galactose-induced aging model through cardiac mitophagy Full Text
*A Combination Study of Pre- and Clinical Trial: Seaweed Consumption Reduces Aging-Associated Muscle Loss Full Text
*N-Acetylcysteine Alleviates the Progression of Chronic Kidney Disease: A Three-Year Cohort Study Full Text
Mitophagy Activation by Urolithin A to Target Muscle Aging Full Text

Combinations of Supplements/Treatments
Vitamin B12-folic acid supplementation improves memory by altering mitochondrial dynamics, dendritic arborization, and neurodegeneration in old and amnesic male mice
The Effect of Glycine and N-Acetylcysteine on Oxidative Stress in the Spinal Cord and Skeletal Muscle After Spinal Cord Injury Full Text
An Evaluation of the Effectiveness of Melatonin and n-Acetylcysteine in Cerebral Ischemia-Reperfusion Injury in Adult Rats Full Text
Tomato and Lemon Extracts Synergistically Improve Cognitive Function by Increasing Brain-derived Neurotrophic Factor Levels in Aged Mice Full Text
Preclinical Studies of Canagliflozin, a Sodium-Glucose Co-Transporter 2 Inhibitor, and Donepezil Combined Therapy in Alzheimer’s Disease Full Text
Aerobic exercise combined with chlorogenic acid exerts neuroprotective effects and reverses cognitive decline in Alzheimer’s disease model mice (APP/PS1) via the SIRT1/ /PGC-1α/PPARγ signaling pathway Full Text (Coffee + exercise)

Prescription Supplements

Metformin
Metformin attenuates inflammation and boosts autophagy in the liver and intestine of chronologically aged rats Full Text
*Effects of metformin therapy on HMGB1 levels in rheumatoid arthritis patients Full Text
The Role and Mechanism of Metformin in Inflammatory Diseases Full Text

Rapamycin (sirolimus)
Therapeutic effect of autophagy induced by rapamycin versus intermittent fasting in animal model of fatty liver Full Text
Inhibition of the mTORC1 pathway alleviates adipose tissue fibrosis Full Text
Endothelial cell-specific reduction in mTOR ameliorates age-related arterial and metabolic dysfunction Full Text (not rapamycin, but its effects should be similar)

Miscellaneous Molecules & Prescription Drugs
Anti–NF-κB peptide derived from nuclear acidic protein attenuates ovariectomy-induced osteoporosis in mice Full Text

Other Areas of Interest (in alphabetical order)

Ageing Clocks & other biomarkers of ageing
*ATAC-clock: An aging clock based on chromatin accessibility Full Text
*ExplaiNAble BioLogical Age (ENABL Age): an artificial intelligence framework for interpretable biological age Full Text
*LensAge index as a deep learning-based biological age for self-monitoring the risks of age-related diseases and mortality Full Text

Epigenetics & Cellular Reprogramming
Mammals Accumulate Epigenetic Noise With Age Full Text
In vivo reprogramming leads to premature death linked to hepatic and intestinal failure

Exosomes (small packets of information released by cells)
A Microvesicle Hydrogel to Treat Arthritis
Microvesicles-hydrogel breaks the cycle of cellular senescence by improving mitochondrial function to treat osteoarthritis Full Text
Plant-derived nanovesicles: harnessing nature's power for tissue protection and repair Full Text
Extracellular Delivery of Functional Mitochondria Rescues the Dysfunction of CD4+ T Cells in Aging Full Text

Genetics including CRISPR
Genetics of human longevity: From variants to genes to pathways Full Text
NeuroD1 administration ameliorated neuroinflammation and boosted neurogenesis in a mouse model of subarachnoid hemorrhage Full Text
Cpt1a silencing in AgRP neurons improves cognitive and physical capacity and promotes healthy aging in male mice Full Text
SIRT2 transgenic over-expression does not impact lifespan in mice Full Text

Klotho Observational Studies
The Longevity Protein Klotho: A Promising Tool to Monitor Lifestyle Improvements Full Text
*L-shaped association of serum α-Klotho and frailty among the middle-aged and older adults: results from NHANES 2007–2016 Full Text
*U-shaped association between serum Klotho and accelerated aging among the middle-aged and elderly US population: a cross-sectional study Full Text
*Relationship between klotho and physical function in healthy aging Full Text

Lifespan Lengthening Interventions
Antibiotics that target mitochondria extend lifespan in C. elegans Full Text
Fermented cereal-origin gerobiotic cocktails promote healthy longevity in Caenorhabditis elegans
Isoleucine Restriction Boosts Lifespan in Mice Abstract

Microbiome
Engraftment of aging-related human gut microbiota and the effect of a seven-species consortium in a pre-clinical model Full Text
Probiotic treatment with Bifidobacterium animalis subsp. lactis LKM512 + arginine improves cognitive flexibility in middle-aged mice Full Text
*Gut microbiome in healthy aging versus those associated with frailty Full Text

Observational Studies
*Social Capital Associates With Better Cognitive Health, Oral Health and Epigenetic Age Deceleration: Findings From the Canadian Longitudinal Study on Aging Full Text
*Self-rated physical health predicts mortality in aging persons beyond objective health risks Full Text
*Improvement of frailty prevalence: difference in factors affecting frailty prevalence among 75 year-old individuals between 2006 and 2019 Full Text

Opinion/Editorials/Theory
Was Mammals’ Longevity Shaped by Living Among Dinosaurs? Full Text
The economics of aging with infectious and chronic diseases

Other Ageing Biology
Parental age effect on the longevity and healthspan in Drosophila melanogaster and Caenorhabditis elegans Full Text
Cartilage tissues regulate systemic aging via ectonucleotide pyrophosphatase/phosphodiesterase 1 in mice Full Text
GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21 Full Text

Regenerative Medicine
'Super melanin' heals skin injuries from sunburn, chemical burns Full Text

Reproductive Health
Cordycepin delays postovulatory aging of oocytes through inhibition of maternal mRNAs degradation via DCP1A polyadenylation suppression Full Text
SIRT6 deficiency causes ovarian hypoplasia by affecting Plod1-related collagen formation Full Text

Reviews
Some HIV-Fighting Drugs May Also Fight Aging Full Text
Mitochondrial-Derived Peptides in Cardiovascular Disease: Novel Insights and Therapeutic Opportunities Full Text
Healthy ageing: Herpes zoster infection and the role of zoster vaccination Full Text
Interventions to Attenuate Cardiovascular Calcification Progression: A Systematic Review of Randomized Clinical Trials Full Text

Senolytics/Senescent Cells
Senolytics May Work Against Long COVID in the Brain Full Text
Current senolytics: mode of action, efficacy and limitations, and their future Full Text
*Translating the Biology of Aging into New Therapeutics for Alzheimer’s Disease: Senolytics Full Text (October 2023) Good summary, also details the results of a clinical trial which was behind a paywall

Skin & Beauty
Electric currents of 448 kHz upregulate anti-senescence pathways in human dermal fibroblasts Full Text
Collagen study advances for photoaging skin Full Text
Human Skin Aging and the Anti-Aging Properties of Retinol Full Text

Sleep Observational Studies
*Sleep regularity and mortality: a prospective analysis in the UK Biobank Full Text
*Daytime napping, biological aging and cognitive function among middle-aged and older Chinese: insights from the China health and retirement longitudinal study Full Text
*Association Between Sleep Traits and Biological Aging Risk: A Mendelian Randomization Study Based on 157,227 Cases and 179,332 Controls

Stem Cells
Mesenchymal Stem Cells in the Pathogenesis and Therapy of Autoimmune and Autoinflammatory Diseases Full Text
The Epigenetic Regulation of Quiescent in Stem Cells Full Text

Telomeres
A novel nutraceutical formulation increases telomere length and activates telomerase activity in middle‑aged rats Full Text
*Can Antidiabetic Medications Affect Telomere Length in Patients with Type 2 Diabetes? A Mini-Review Full Text

Odds & Sods
*Social connectedness, functional capacity, and longevity: A focus on positive relations with others Full Text
*Survival and longevity of European rulers: geographical influences and exploring potential factors, including the Mediterranean diet — a historical analysis from 1354 to the twentieth century Full Text
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***Disclaimer 1 – I am NOT a doctor or indeed a scientist. All the information pertained within is for information purposes only; use at your own risk. Please consult with a healthcare practitioner if you need medical advice.***

*Also bear in mind that most of the studies mentioned above are in rodents, not humans. Rodents, needless to say, do not always react the same way to drugs as humans do – witness the countless times cancer or another disease has been cured in rodents only to subsequently fail human trials. I have *starred any human trials.*
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Chris Linnell's Longevity Review Newsletter - December 2023 Longevity Review 30 January 2024 - 09:30 PM

As we wrapped up the year and took a well deserved holiday break, the longevity studies kept on coming. This month we will take a look at the latest results from the ITP, the gold standard of longevity studies; how CD38 is a prime culprit for ovarian ageing and lung fibrosis, and how it can be counteracted; how high consumption of fruits and vegetables increases mouse average lifespan; and, how a new substance, originally from carrots, increases the healthspan of elderly mice.

In addition, in the supplemental section, you’ll find reviews collagen for skin, magnesium for muscles and NAC for the arteries; how drinking tea reduces biological age; how fisetin improves arterial function; how organs age at different rates; and even how the lifespan of bumblebees can be extended! Plus of course much more.

Canadian Longevity Association News

December saw two new volunteers, Elizabeth and Tayseer, join our growing team - so a warm welcome to them both! We also received our first major (for us) donation, which will allow us to expand our activities in 2024. In addition, we had our first Christmas longevity dinner, which turned out to be a great success with 17 people attending. If you’re in Toronto, make sure to join next year’s one!

Donate to the Canadian Longevity Association

Please also follow, or join us on social media so that we can grow our reach:

Twitter/X (I also have a personal account with more frequent longevity updates)

Facebook Instagram LinkedIn Meetup

Canadian Longevity Association YouTube Channel - where you can find video talk-throughs of these reviews.

Discord for longevity related chats and the place to have all your longevity related questions answered.

December 2023 Round-Up:

It's always a good day when the Interventions Testing Program releases a new set of results, especially when a couple of the molecules are shown to extend median lifespan - and extra especially if one of those molecules is a supplement I take!
In this latest release, astaxanthin (which I take) increased median lifespan in males by 12%, while meclizine increased it by 8%. Unfortunately, the results were sex specific. Also unfortunately, fisetin, SG1002 (hydrogen sulfide donor), dimethyl fumarate, mycophenolic acid, and 4-phenylbutyrate did not show a statistically significant change at the doses tested.
Astaxanthin and Meclizine Extend Lifespan in Mice
Astaxanthin and meclizine extend lifespan in UM-HET3 male mice; fisetin, SG1002 (hydrogen sulfide donor), dimethyl fumarate, mycophenolic acid, and 4-phenylbutyrate do not significantly affect lifespan in either sex at the doses and schedules used Full Text

We all know that fruit & vegetables (F&V) are good for us, but here is the first study to show what elevated consumption of F&V does over the course of an entire life. Mice were fed high or low fat diets, with or without high levels of F&V, and those with high F&V had a higher median lifespan, lower tumor incidence and improvements in various other biomarkers.
Life-long consumption of high level of fruits and vegetables reduces tumor incidence and extends median lifespan in mice Full Text

Originally found in carrots, isofalcarintriol extended the lifespan of worms, and improved glucose metabolism and exercise endurance while decreasing frailty in mice. Although it didn’t extend lifespan in mice, it’s beneficial effects were observed at very low doses which could indicate that its bioavailability is much better than similar natural substances such as resveratrol.
A naturally occurring polyacetylene isolated from carrots promotes health and delays signatures of aging Full Text

Ovaries are the first major organ to succumb to ageing, leading to much earlier female age-related infertility. The main culprit, according to the first paper, is elevated levels of CD38, which deplete NAD+ and which can be reversed by a CD38 inhibitor, c78, leading to improved egg quality and increased litter size in aged mice. The second paper unveils a new CD38 inhibitor, Ab68, which prevents fibrosis in mice and might be superior for potential side effects as it does not cross the blood-brain barrier.
Heavy-chain antibody targeting of CD38 NAD+ hydrolase ectoenzyme to prevent fibrosis in multiple organs Full Text
NADase CD38 is a key determinant of ovarian aging Full Text

Supplemental Section

Lifestyle
*Impact of 8 lifestyle factors on mortality and life expectancy among United States veterans: The Million Veteran Program

Fasting/Dietary Restriction – certainly the cheapest & also one of the most effective anti-ageing interventions currently available. It comes in many flavours, but I fast for at least 12 hours every day.
*Earlier Meals Associated with Less Vascular Disease Full Text
Exercise and Caloric Restriction Exert Different Benefits on Skeletal Muscle Metabolism in Aging Condition Full Text
A long-term ketogenic diet in young and aged rats has dissociable effects on prelimbic cortex and CA3 ensemble activity Full Text

Diet – let food be thy medicine…
*Adherence to the EAT-Lancet reference diet is associated with a reduced risk of incident cancer and all-cause mortality in UK adults Full Text
*The Southern European Atlantic diet and all-cause and cause-specific mortality: a European multicohort study Full Text
*Tea consumption and attenuation of biological aging: a longitudinal analysis from two cohort studies Full Text (Nov 2023)

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*Different resistance training volumes on strength, functional fitness, and body composition of older people: A systematic review with meta-analysis
*The association between chrononutrition behaviors and muscle health among older adults: The study of muscle, mobility and aging Full Text
*An acute bout of high-intensity exercise affects nocturnal sleep and sleep-dependent memory consolidation Full Text

Astaxanthin – which is behind the pink colour of salmon & shrimp. Considered the most powerful carotenoid, it has anti-oxidative, anti-inflammatory, anti-cancer, neuro-protective and skin-protective qualities.
Astaxanthin Protects against Alcoholic Liver Injury via Regulating Mitochondrial Redox Balance and Calcium Homeostasis
Dietary Astaxanthin: A Promising Antioxidant and Anti-Inflammatory Agent for Brain Aging and Adult Neurogenesis Full Text

Curcumin – the spice which gives curries their yellow colour. Anti-inflammatory and neuroprotective. Needs to be taken with black pepper (piperine) to improve bioavailability.
*The effects of curcumin-piperine supplementation on inflammatory, oxidative stress and metabolic indices in patients with ischemic stroke in the rehabilitation phase: a randomized controlled trial Full Text
Targeted therapies of curcumin focus on its therapeutic benefits in cancers and human health: Molecular signaling pathway-based approaches and future perspectives Full Text
Anti-inflammatory effect of curcumin in an accelerated senescence model of Wistar rat: an in vivo and in-silico study

Fisetin
Exploring the anti-aging effects of fisetin in telomerase-deficient progeria mouse model Full Text
Fisetin, a dietary flavonoid, promotes transintestinal cholesterol excretion through the activation of PPARδ
Fisetin Inhibits UVA-Induced Expression of MMP-1 and MMP-3 through the NOX/ROS/MAPK Pathway in Human Dermal Fibroblasts and Human Epidermal Keratinocytes Full Text

Melatonin
*Melatonin supplementation does not alter vascular function or oxidative stress in healthy normotensive adults on a high sodium diet Full Text
Melatonin facts: Lack of evidence that melatonin is a radical scavenger in living systems Full Text
Melatonin as a chronobiotic/cytoprotective agent in bone. Doses involved Full Text

Nicotinamide MonoNucleotide (NMN)
Nicotinamide mononucleotide as a therapeutic agent to alleviate multi-organ failure in sepsis Full Text
Nicotinamide mononucleotide alleviates endotoxin-induced acute lung injury by modulating macrophage polarization via the SIRT1/NF-κB pathway Full Text
The identification of new roles for nicotinamide mononucleotide after spinal cord injury in mice: an RNA-seq and global gene expression study Full Text

Nicotinamide Riboside (NR)
Chronic dietary supplementation with nicotinamide riboside reduces sleep need in the laboratory mouse Full Text

Pterostilbene
Pterostilbene alleviates abdominal aortic aneurysm via inhibiting macrophage pyroptosis by activating the miR-146a-5p/TRAF6 axis
Stilbenes: a promising small molecule modulator for epigenetic regulation in human diseases Full Text

Resveratrol
Cardiovascular risk of dietary trimethylamine oxide precursors and the therapeutic potential of resveratrol and its derivatives Full Text
Resveratrol and Gut Microbiota Synergy: Preventive and Therapeutic Effects Full Text
Prophylactic oral application of resveratrol to alleviate acute campylobacteriosis in human gut microbiota associated IL-10−/− mice Full Text

Spermidine
Metabolism of Polyamines and Kidney Disease: A Promising Therapeutic Target Full Text

Other available supplements or natural substances (in alphabetical order)
*Daily low-dose aspirin and incident type 2 diabetes in community-dwelling healthy older adults: a post-hoc analysis of efficacy and safety in the ASPREE randomised placebo-controlled trial
Therapeutic Applications of Ginseng Natural Compounds for Health Management Full Text
*Supplementation with β-hydroxy-β-methylbutyrate after resistance training in post-acute care patients with sarcopenia: A randomized, double-blind placebo-controlled trial
The Integral Role of Magnesium in Muscle Integrity and Aging: A Comprehensive Review Full Text
N-Acetylcysteine and Atherosclerosis: Promises and Challenges Full Text
*Omega-3 Blood Levels and Stroke Risk: A Pooled and Harmonized Analysis of 183 291 Participants From 29 Prospective Studies Full Text
Traditional herbs: mechanisms to combat cellular senescence Full Text
Preventative and therapeutic potential of tocotrienols on musculoskeletal diseases in ageing Full Text

Combinations of Supplements/Treatments
Geroprotector drugs and exercise: friends or foes on healthy longevity? Full Text
Reprogramming Macrophage Polarization, Depleting ROS by Astaxanthin and Thioketal-Containing Polymers Delivering Rapamycin for Osteoarthritis Treatment Full Text
*Combined Rehabilitation with Alpha Lipoic Acid, Acetyl-L-Carnitine, Resveratrol, and Cholecalciferolin Discogenic Sciatica in Young People: A Randomized Clinical Trial Full Text

Prescription Supplements

Metformin
*The effect of metformin on adipokines levels: A systematic review and meta-analysis of randomized-controlled trials
*Metformin reduces decline in the estimated glomerular filtration rate during progression of autosomal dominant polycystic kidney disease: a systematic review and meta-analysis Full Text

Miscellaneous Molecules & Prescription Drugs
BIO101 stimulates myoblast differentiation and improves muscle function in adult and old mice Full Text
Cabozantinib prevents AGEs-induced degradation of type 2 collagen and aggrecan in human chondrocytes Full Text
*Statins, Mortality, and Major Adverse Cardiovascular Events Among US Veterans With Chronic Kidney Disease Full Text
*Statins and cognitive decline in patients with Alzheimer’s and mixed dementia: a longitudinal registry-based cohort study Full Text

Other Areas of Interest (in alphabetical order)

Ageing Clocks & other biomarkers of ageing
*Organ aging signatures in the plasma proteome track health and disease Full Text
*Associations between biological ageing and the risk of, genetic susceptibility to, and life expectancy associated with rheumatoid arthritis: a secondary analysis of two observational studies Full Text
*Predicting 1-, 3-, 5-, and 8-year all-cause mortality in a community-dwelling older adult cohort: relevance for predictive, preventive, and personalized medicine Full Text

Blood Factors or other Heterochronic Transplantation
Supernatant of activated platelet-rich plasma rejuvenated aging-induced hyposalivation in mouse Full Text
Rejuvenation of cerebromicrovascular function in aged mice through heterochronic parabiosis: insights into neurovascular coupling and the impact of young blood factors

Epigenetics & Cellular Reprogramming
Partial cellular reprogramming: A deep dive into an emerging rejuvenation technology Full Text
DNA methylation rates scale with maximum lifespan across mammals Full Text
Sustained Vision Recovery by OSK Gene Therapy in a Mouse Model of Glaucoma

Exosomes (small packets of information released by cells)
Effect of miR-21 in mesenchymal stem cells-derived extracellular vesicles behavior Full Text
Extracellular vesicles (EVs): A promising therapeutic tool in the heart tissue regeneration Full Text

Genetics including CRISPR
*Evidence for the role of selection for reproductively advantageous alleles in human aging Full Text
*Genetic associations with longevity are on average stronger in females than in males Full Text
*Genetic insights into the association of statin and newer nonstatin drug target genes with human longevity: a Mendelian randomization analysis Full Text

Lifespan Lengthening Interventions
DNA methylation extends lifespan in the bumblebee Bombus terrestris Full Text
Anti-aging Effect of Rutin in Caenorhabditis elegans and D-Gal-Induced Aging Mouse Model
SKN-1/NRF2 upregulation by vitamin A is conserved from nematodes to mammals and is critical for lifespan extension in Caenorhabditis elegans Full Text

Microbiome
Probiotics Attenuate Myopathic Changes in Aging Rats via Activation of the Myogenic Stellate Cells Full Text
*Disentangling the age-related manner in the associations between gut microbiome and women’s health: a multi-cohort microbiome study Full Text
Targeting gut microbiota in aging-related cardiovascular dysfunction: focus on the mechanisms Full Text

Observational Studies
*Low-density-lipoprotein cholesterol and mortality outcomes among healthy older adults: A post-hoc analysis of ASPREE trial Full Text
*The Phenotypic Characterization of the Oldest Italian Man from December 28, 2020, to September 23, 2021, A.T., Strengthens the Idea That the Immune System can Play a Key Role in the Attainment of Extreme Longevity Full Text
*Does urban greenness reduce loneliness and social isolation among Canadians? A cross-sectional study of middle-aged and older adults of the Canadian Longitudinal Study on Aging (CLSA) Full Text

Opinion/Editorials/Theory
Leveraging AI to identify dual-purpose aging and disease targets Full Text
Enabling translational geroscience by broadening the scope of geriatric care Full Text
Three common assumptions about inflammation, aging, and health that are probably wrong
Healthy aging: Linking causal mechanisms with holistic outcomes Full Text

Other Ageing Biology
Recapitulation of anti-aging phenotypes by global overexpression of PTEN in mice Full Text
Systematic assessment of transcriptomic and metabolic reprogramming by blue light exposure coupled with aging Full Text

Reproductive Health
Impact of NAD+ metabolism on ovarian aging Full Text
Delivering umbilical cord mesenchymal stem cell exosomes through hydrogel ameliorates vaginal atrophy in ovariectomized rats Full Text

Reviews
Aging Hallmarks and Progression and Age-Related Diseases: A Landscape View of Research Advancement Full Text
The regulatory effect of growth differentiation factor 11 on different cells Full Text
Umbrella review and Delphi study on modifiable factors for dementia risk reduction Full Text
PCSK9: an emerging player in cardiometabolic aging and its potential as a therapeutic target and biomarker Full Text
Metabolic pathways in immune senescence and inflammaging: Novel therapeutic strategy for chronic inflammatory lung diseases. An EAACI position paper from the Task Force for Immunopharmacology Full Text
Age-Related Alternative Splicing: Driver or Passenger in the Aging Process? Full Text

Senolytics/Senescent Cells
Senotherapeutic drug treatment ameliorates chemotherapy-induced cachexia Full Text
Intermittent supplementation with fisetin improves arterial function in old mice by decreasing cellular senescence Full Text
Non-Intrinsic, Systemic Mechanisms of Cellular Senescence Full Text

Skin & Beauty
Umbilical cord-derived mesenchymal stem cell secretome promotes skin regeneration and rejuvenation: From mechanism to therapeutics Full Text
*Exploring the Impact of Hydrolyzed Collagen Oral Supplementation on Skin Rejuvenation: A Systematic Review and Meta-Analysis Full Text
*Immunomodulation with AM3 and antioxidants creates an adequate framework for skin repair and decreases the monocyte proinflammatory stage in smoker women Full Text

Stem Cells
Endothelial progenitor cells systemic administration alleviates multi-organ senescence by down-regulating USP7/p300 pathway in chronic obstructive pulmonary disease Full Text
Rewiring of IGF1 secretion and enhanced IGF1R signaling induced by co-chaperone carboxyl-terminus of Hsp70 interacting protein in adipose-derived stem cells provide augmented cardioprotection in aging-hypertensive rats Full Text
Mesenchymal stem cells lose the senescent phenotype under 3D cultivation Full Text

Telomeres
*Unraveling the causal genes and transcriptomic determinants of human telomere length Full Text
Diet and Aging: The Role of Polyphenol-Rich Diets in Slow Down the Shortening of Telomeres: A Review Full Text

Odds & Sods
Exergames improve cognitive function in older adults and their possible mechanisms: A systematic review Full Text
Songbirds avoid the oxidative stress costs of high blood glucose levels: a comparative study Full Text
Optimum ratio of dietary protein and carbohydrate that maximises lifespan is shared among related insect species Full Text
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***Disclaimer 1 – I am NOT a doctor or indeed a scientist. All the information pertained within is for information purposes only; use at your own risk. Please consult with a healthcare practitioner if you need medical advice.***

Chris Linnell's Longevity Review Newsletter - October 2023 Longevity Review 25 November 2023 - 01:08 AM

Hello and welcome again to this month’s longevity review. The big news this month is that exosomes (small packets of chemical information cells use to communicate with each other) from young pig plasma were able to cross the species barrier and rejuvenate certain biomarkers in old rats. In addition, a small molecule was found to help repair older tendon injuries, a post conception rejuvenation event was confirmed in humans with big implications, and it was shown that the very old (+85) are still able to gain muscle mass and strength.

In the supplemental section, you’ll find the unsurprising news that alcohol and vaping accelerate epigenetic ageing, NMN and spermidine for reproductive health, reviews of glycine and resveratrol, how vaccinations can reduce incidence of dementia, hyperbaric oxygen therapy to improve bone health, and how in the last century the health and lifespan of marine mammals in captivity have mirrored the advances seen in humans. Plus of course much more!

Canadian Longevity Association News

The CLA celebrated International Longevity Day on the 1st of October with a photo in front of the 3D Toronto sign in Nathan Philip’s Square in Toronto, followed by drinks and discussion at a nearby venue. We had a banner of our logo specially printed for the photos. This event kicked off regular monthly meetups in Toronto - details of future events can be found on our FB group, LinkedIn page and newly resurrected Meetup group. Come and join us if you are around!
The CLA also attended a fantastic conference in Hamilton called Next Great Big Ideas, where some potentially very useful contacts were made. We also expanded our outreach, with some interesting developments slated for the new year - watch this space!

Donate to the Canadian Longevity Association

Please also follow, or join us on social media so that we can grow our reach:

Twitter/X (I also have a personal account with more frequent longevity updates)

Facebook
Instagram
LinkedIn
Meetup

Canadian Longevity Association YouTube Channel - where you can find video talk-throughs of these reviews.

Discord for longevity related chats and the place to have all your longevity related questions answered.

October 2023 Round-Up:

I was super excited to read this paper, which almost falls into the too good to be true category. I’ve been following this research from the beginning and one of the primary leads is a reader of this newsletter, so risk of bias alert! In a nutshell, using a youthful plasma fraction containing an abundance of exosomes (small packets of chemical information cells use to communicate with each other), they cut the epigenetic age of rats by more than half and various other biomarkers returned to youthful levels. Equally noteworthy, the plasma fraction came from young pigs! This suggests that this modality crosses the species barrier and thus could also potentially be used for us, removing any ethical concerns and availability issues. The group are next validating this in dogs, which if equally efficacious will lead to human trials.
Plasma from Young Pigs Halves Old Rats’ Epigenetic Age Full Text

Damaged tendons are a major source of disability, which increases with age as their regenerative capacity decreases. Using machine learning, researchers discovered a natural small molecule, POG, that could improve the regenerative capacity of old tendons by decreasing senescence and inflammation, and increasing autophagy via suppressing mTOR and NF-kb. This was achieved either systematically or by localised injection for torn tendon repair, and by utilising a biomaterial scaffold for complete tendon cuts in rats. Results were replicated using older human tendon cell samples. This is a promising avenue for people to maintain or recover their activity levels in older ages.
Prim-O-glucosylcimifugin ameliorates aging-impaired endogenous tendon regeneration by rejuvenating senescent tendon stem/progenitor cells Full Text

A very important, but underappreciated paper in my view, which has some quite profound implications. Building on work in mice, this paper potentially confirms in humans that there is a rejuvenation event following conception. We are all born much biologically younger than the spermatozoa and ovum we originated from - a newborn looks like a newborn, not aged like its parents! This paper indicates that this rejuvenation event occurs 14 to 21 days after fertilisation, and is the moment we start to age. So, if we’ve already been rejuvenated once in our lives, why can’t science eventually rejuvenate us again?
Intersection clock reveals a rejuvenation event during human embryogenesis Full Text

Finally, onto a study applicable in the here and now. Loss of muscle mass not only leads to frailty, but is also associated with mortality. However, there is a common fear that people become too old to gain benefit from resistance exercise. This study should dispel that, as it showed that +85 year olds gained just as much muscle mass and strength as those 65-75, with both groups increasing muscle mass by around 10% and strength by 46% & 38% respectively over 12 weeks of 3x per week whole body progressive resistance training at 60%-80% 1 repetition maximum.
*Muscle Mass and Strength Gains Following Resistance Exercise Training in Older Adults 65–75 Years and Older Adults Above 85 Years Full Text

Supplemental Section

Lifestyle
*Association between a mediterranean lifestyle and Type 2 diabetes incidence: a prospective UK biobank study Full Text
*Association of a healthy lifestyle with mortality in older people Full Text
*Healthy lifestyle in late-life, longevity genes, and life expectancy among older adults: a 20-year, population-based, prospective cohort study Full Text

Fasting/Dietary Restriction – certainly the cheapest & also one of the most effective anti-ageing interventions currently available. It comes in many flavours, but I fast for at least 12 hours every day.
*Calorie restriction modulates the transcription of genes related to stress response and longevity in human muscle: The CALERIE study Full Text
*Diet composition, adherence to calorie restriction, and cardiometabolic disease risk modification Full Text
*Effect of Time-Restricted Eating on Weight Loss in Adults With Type 2 Diabetes Full Text

Diet – let food be thy medicine…
*Diet strategies for promoting healthy aging and longevity: An epidemiological perspective Full Text
*Relationship between Composite Dietary Antioxidant Index and Aging Full Text
*The effects of olive oil consumption on cognitive performance: a systematic review Full Text

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*Dose–response effects of resistance training on physical function in frail older Chinese adults: A randomized controlled trial Full Text
*Effect of resistance training volume on body adiposity, metabolic risk, and inflammation in postmenopausal and older females: Systematic review and meta-analysis of randomized controlled trials Full Text

Astaxanthin – which is behind the pink colour of salmon & shrimp. Considered the most powerful carotenoid, it has anti-oxidative, anti-inflammatory, anti-cancer, neuro-protective and skin-protective qualities.
*Astaxanthin supplementation impact on insulin resistance, lipid profile, blood pressure, and oxidative stress in polycystic ovary syndrome patients: A triple-blind randomized clinical trial
Astaxanthin protects human ARPE-19 retinal pigment epithelium cells from blue light-induced phototoxicity by scavenging singlet oxygen
Astaxanthin promotes locomotor function recovery and attenuates tissue damage in rats following spinal cord injury: a systematic review and trial sequential analysis Full Text

Curcumin – the spice which gives curries their yellow colour. Anti-inflammatory and neuroprotective. Needs to be taken with black pepper (piperine) to improve bioavailability.
Evaluation of oxidative stress indicators as toxicity parameters after chronic exposure of Drosophila melanogaster to free curcumin and curcumin-loaded nanocapsules*
Targeting endothelial cells with golden spice curcumin: A promising therapy for cardiometabolic multimorbidity Full Text

Fisetin
PPARγ activation by fisetin mitigates vascular smooth muscle cell senescence via the mTORC2-FoxO3a-autophagy signaling pathway
DNA hypomethylation by fisetin preserves mitochondria functional genes and contributes to the protection of I/R rat heart

Melatonin
*Significant potential of melatonin therapy in Parkinson’s disease – a meta-analysis of randomized controlled trials Full Text
*The Effects of Melatonin Supplementation on Professional Football Player Performance: A Systematic Review Full Text
Non-Excitatory Amino Acids, Melatonin, and Free Radicals: Examining the Role in Stroke and Aging Full Text

Nicotinamide MonoNucleotide (NMN)
Improving lysosomal ferroptosis with NMN administration protects against heart failure Full Text
Inherited myogenic abilities in muscle precursor cells defined by the mitochondrial complex I-encoding protein Full Text
Hydroxyapatite-based nano-drug delivery system for nicotinamide mononucleotide (NMN): significantly enhancing NMN bioavailability and replenishing in vivo nicotinamide adenine dinucleotide (NAD+) levels

Nicotinamide Riboside (NR)
NAD+ Precursors: A Physiological Reboot? Full Text
*Long-Term Nicotinamide Riboside Use Improves Coordination and Eye Movements in Ataxia Telangiectasia Full Text

Pterostilbene
Changes in brown adipose tissue induced by resveratrol and its analogue pterostilbene in rats fed with a high-fat high-fructose diet Full Text

Resveratrol
*Effect of Resveratrol on Endothelial Function in Patients with CKD and Diabetes: A Randomized Controlled Trial
Resveratrol in Rheumatological Diseases: A Systematic Review Full Text
Resveratrol combats chronic diseases through enhancing mitochondrial quality Full Text

Spermidine
Changes in Whole Blood Polyamine Levels and Their Background in Age-Related Diseases and Healthy Longevity Full Text

Other available supplements (in alphabetical order)
*Vitamin C supplementation showed greater effects on systolic blood pressure in hypertensive and diabetic patients: an updated systematic review and meta-analysis of randomised clinical trials
Effects of the Acute and Chronic Administration of Cannabidiol on Cognition in Humans and Animals: A Systematic Review
Cannabidiol Modulates Emotional Function and Brain-Derived Neurotrophic Factor Expression in Middle-Aged Female Rats Exposed to Social Isolation Full Text
Protective Actions of Cannabidiol on Aging-Related Inflammation, Oxidative Stress and Apoptosis Alterations in Liver and Lung of Long Evans Rats Full Text
The Potential of Collagen Treatment for Comorbid Diseases Full Text
*Resistance Exercise and Creatine Supplementation on Fat Mass in Adults < 50 Years of Age: A Systematic Review and Meta-Analysis Full Text
Vitamin D Improves Cognitive Impairment and Alleviates Ferroptosis via the Nrf2 Signaling Pathway in Aging Mice Full Text
*Effects of DHA on cognitive dysfunction in aging and Alzheimer's disease: The mediating roles of ApoE Full Text
The effect of glycine administration on the characteristics of physiological systems in human adults: A systematic review Full Text
*Cognitive impact of multidomain intervention and omega 3 according to blood Aβ42/40 ratio: a subgroup analysis from the randomized MAPT trial Full Text
Unraveling the impact of Omega-3 polyunsaturated fatty acids on blood-brain barrier (BBB) integrity and glymphatic function Full Text
*Early Intervention in Cognitive Aging with Strawberry Supplementation Full Text
Pharmacological Effects of Urolithin A and Its Role in Muscle Health and Performance: Current Knowledge and Prospects Full Text
Overview of Ursolic Acid Potential for the Treatment of Metabolic Disorders, Autoimmune Diseases, and Cancers via Nuclear Receptor Pathways Full Text

Combinations of Supplements
The Combination of Citicoline and Nicotinamide Mononucleotide Induces Neurite Outgrowth and Mitigates Vascular Cognitive Impairment via SIRT1/CREB Pathway
Treatment of stroke in aged male and female rats with Vepoloxamer and tPA reduces neurovascular damage Full Text
Nicotinamide Riboside and Phycocyanin Oligopeptides Affect Stress Susceptibility in Chronic Corticosterone-Exposed Rats Full Text
Combination of curcumin and catalase protects against chondrocyte injury and knee osteoarthritis progression by suppressing oxidative stress Full Text

Prescription Supplements

Metformin
*Heterogeneous treatment effects of metformin on risk of dementia in patients with type 2 diabetes: A longitudinal observational study Full Text
*Metformin, age-related cognitive decline, and brain pathology
Old drug, new tricks: the utility of metformin in infection and vaccination responses to influenza and SARS-CoV-2 in older adults Full Text

Rapamycin (sirolimus)
Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease Full Text
Rapamycin Responds to Alzheimer’s Disease: A Potential Translational Therapy Full Text
Mechanistic target of rapamycin (mTOR): a potential new therapeutic target for rheumatoid arthritis Full Text

Miscellaneous Molecules & Prescription Drugs
Head-to-head comparison of BAM15, semaglutide, rosiglitazone, NEN, and calorie restriction on metabolic physiology in female db/db mice Full Text
A short peptide protects from age-onset proteotoxicity Full Text
The Effect of Liraglutide on Lung Cancer and Its Potential Protective Effect on High Glucose-Induced Lung Senescence and Oxidative Damage Full Text
Omentin-1 ameliorates the progress of osteoarthritis by promoting IL-4-dependent anti-inflammatory responses and M2 macrophage polarization Full Text
SGLT inhibitors for improving healthspan and lifespan Full Text

Other Areas of Interest (in alphabetical order)

Ageing Clocks & other biomarkers of ageing
*HOMA-IR is positively correlated with biological age and advanced aging in the US adult population Full Text
*Alcohol consumption and epigenetic age acceleration across human adulthood Full Text
*Accelerated epigenetic age, inflammation, and gene expression in lung: comparisons of smokers and vapers with non-smokers Full Text

Epigenetics & Cellular Reprogramming
*Blood DNA methylation signature of diet quality, and association with cardiometabolic traits Full Text

Exosomes (small packets of chemical information released by cells)
Nanotopographical Cues Tune the Therapeutic Potential of Extracellular Vesicles for the Treatment of Aged Skeletal Muscle Injuries Full Text
Extracellular Vesicles Derived from Osteogenic-Differentiated Human Bone Marrow-Derived Mesenchymal Cells Rescue Osteogenic Ability of Bone Marrow-Derived Mesenchymal Cells Impaired by Hypoxia Full Text

Genetics including CRISPR
Human Presenilin-1 delivered by AAV9 rescues impaired γ-secretase activity, memory deficits, and neurodegeneration in Psen mutant mice Full Text
Duplications of human longevity-associated genes across placental mammals Full Text
Genome-wide CRISPR activation screening in senescent cells reveals SOX5 as a driver and therapeutic target of rejuvenation

Lifespan Lengthening Interventions
Lactobacillus paracasei HII01 enhances lifespan and promotes neuroprotection in Caenorhabditis elegans Full Text
Thiadiazolidinone (TDZD) Analogs Inhibit Aggregation-Mediated Pathology in Diverse Neurodegeneration Models, and Extend C. elegans Life- and Healthspan Full Text
Hesperidin ameliorates Amyloid-β toxicity and enhances oxidative stress resistance and lifespan of Caenorhabditis elegans through acr-16 mediated activation of the autophagy pathway

Microbiome
*Effects of heat-killed Lactiplantibacillus plantarum TWK10 on exercise performance, fatigue, and muscle growth in healthy male adults Full Text
Bifidobacterium bifidum and Lactobacillus paracasei alleviate sarcopenia and cognitive impairment in aged mice by regulating gut microbiota-mediated AKT, NF-κB, and FOXO3a signaling pathways Full Text
Influence of gut microbiota on the development of most prevalent neurodegenerative dementias and the potential effect of probiotics in elderly: A scoping review Full Text

Observational Studies
*The association of herpes zoster and influenza vaccinations with the risk of developing dementia: a population-based cohort study within the UK Clinical Practice Research Datalink Full Text
*Association between daily alcohol consumption and serum alpha klotho levels among U.S. adults over 40 years old: a cross-sectional study Full Text
*Lower serum Klotho level and higher systemic immune-inflammation index: an inverse correlation Full Text
*Resting heart rate, cognitive function, and inflammation in older adults: a population-based study Full Text
*Serum Cholesterol and Impact of Age on Coronary Heart Disease Death in More Than 4 Million Veterans Full Text

Opinion/Editorials/Theory
Directional selection coupled with kin selection favors the establishment of senescence Full Text
Disease-modifying drugs for Alzheimer disease: implications for people in Canada Full Text

Other Ageing Biology
*AgingReG: a curated database of aging regulatory relationships in humans Full Text
HALL: a comprehensive database for human aging and longevity studies Full Text
A comprehensive AI-driven analysis of large-scale omic datasets reveals novel dual-purpose targets for the treatment of cancer and aging Full Text

Regenerative Medicine
Multi-species atlas resolves an axolotl limb development and regeneration paradox Full Text

Reproductive Health
β-nicotinamide mononucleotide rescues the quality of aged oocyte and improves subsequent embryo development in pigs Full Text
Spermidine May Improve Egg Health and Fertility Abstract
*Influence of Melatonin Treatment on Emotion, Sleep, and Life Quality in Perimenopausal Women: A Clinical Study Full Text

Reviews
The several ways to authentically cure Alzheimer’s dementia Full Text
A Narrative Review: The Effect and Importance of Carotenoids on Aging and Aging-Related Diseases Full Text
Mitochondria: A Potential Rejuvenation Tool against Aging Full Text

Senolytics/Senescent Cells
Senescent Schwann cells induced by aging and chronic denervation impair axonal regeneration following peripheral nerve injury Full Text
Senolytics prevent caveolar CaV3.2-RyR axis malfunction in old vascular smooth muscle Full Text
Potential Clinical Implications of Senotherapies for Cardiovascular Disease Full Text
*Biomarkers of cellular senescence and risk of death in humans Full Text

Skin & Beauty
*Low-molecular-weight collagen peptides supplement promotes a healthy skin: A randomized, double-blinded, placebo-controlled study Full Text
Skin ageing and topical rejuvenation strategies Full Text
*The Benefits of a Multimechanistic Antiaging Skin Technology Full Text

Stem Cells
How Nutrition Regulates Hematopoietic Stem Cell Features Full Text

Telomeres
*Differential Effects of Very-Low-Volume Exercise Modalities on Telomere Length, Inflammation, and Cardiometabolic Health in Obese Metabolic Syndrome Patients: A Subanalysis from Two Randomized Controlled Trials Full Text
Telomouse—a mouse model with human-length telomeres generated by a single amino acid change in RTEL1 Full Text
*The association of leukocyte telomere length with exceptional longevity among older women

Odds & Sods
*Effectiveness of photobiomodulation for people with age-related cognitive impairment: a systematic review and meta-analysis
Survival improvements of marine mammals in zoological institutions mirror historical advances in human longevity Full Text
Hyperbaric Oxygen Therapy Improves Bone Health in Rats Abstract
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***Disclaimer 1 – I am NOT a doctor or indeed a scientist. All the information pertained within is for information purposes only; use at your own risk. Please consult with a healthcare practitioner if you need medical advice.***

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