July 2024 Longevity Review

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!

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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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