LONGECITY Blogs RSS feed Last Updated: 25 December 2024 - 12:18 PM

In a bid to finally catch up with these Longevity Reviews, I took the decision to combine the results for September and October. This led to a fair amount of hand wringing as I sought to include only the biggest and most important studies for those two months, but my final selection for the Highlights Sections sees us taking a look at the most comprehensive dietary restriction study in mice to date; how the rat lifespan record might have been broken with exosome treatment; how an inhibitor of hyaluronan synthesis increases lifespan in mice; how exercise intensity is more important than volume for mortality reduction and, in the Canadian Content Study, how a protector of neurons plays a greater role in lifespan.

As a result of this merger, the supplemental section is bigger than normal. I tried to condense it as much as possible, but there were just too many studies that had to be included. Therefore, as a brief taster, you’ll find in Lifestyle the link between cardiovascular health and cancer mortality; in Fasting, how eating late affects blood glucose; in Diet, how dietary diversity affects aging; in other Supplements, reviews of Hesperetin & NAC; in Metformin, how it slows down aging in non-human primates; in Epigenetics, reprogramming senescent cells extends mouse lifespan; in Genetics, the use of CRISPR to find new ways to rejuvenate brain stem cells; in Opinion, some new theories on aging; in Reproductive Health, how genistein can help with menopause; and finally, in Telomeres, how astragalus increased telomere length in a human trial. (To make these suggestions easier to find, I’ve marked them with ***)

NOTE: The original post was too long, so I have split the Supplemental Section in two to accomodate the limit.

Canadian Longevity Association News

The big news over the last two months is that we’ve opened up an online shop!

That’s right, just in time for Christmas, you have all your shopping needs sorted! LOL

But seriously, you can now help fund the CLA’s activities, while sporting our logo on a wide and growing range of apparel. Take a look at our shop and if there is anything missing that you’d like to purchase, then drop us a line and we’ll happily and quickly add it.

Link to the CLA’s Online Store

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.

Sep/Oct 2024 Highlights:

In the largest comparative study of different forms of dietary restriction in female mice, scientists from CALICO discovered some really interesting and puzzling results. They studied 20% and 40% caloric restriction, as well as 1 and 2 days a week fasting. The median and maximum respectively for each compared to the control were as follows: 20CR: 18% & 22%; 40CR: 36% & 38%; 1DF: 12% & 6%; 2DF: 11% & 15%.

The 40% caloric restriction mice were clearly the winners, but changes to their immune system might make them more susceptible to infection. Another big puzzle was that lower weight and fat was better in early life, but then reversed in late life. As the authors put it, “DR extends lifespan while decreasing body weight and fat mass, yet preserving body weight and fat mass is associated with longer lifespan. This paradox is a recurrent theme in this study.”

This is a really in depth and readable study, and I do recommend that you take a look at it.
Study probes how eating less can extend lifespan Full Text

A research group who have been following since they started out, and who I have covered several times in these highlights, have released their latest results. E5, a young blood plasma fraction mainly consisting of exosomes, was previously shown to reduce the epigenetic age and improve various biomarkers in rats. This new study, along with once again showing improved biomarkers and grip strength, takes it further by including lifespan. And, the result of that was that the median lifespan improved by 9.7% over controls. More tantalizingly, one of the rats potentially broke the rat lifespan record for this strain, dying at the age of 48 months, which was a 21.7% increase over the longest lived control rat!

This was a very small study, with only 8 rats in each group, however I believe this to have great potential. Especially as they used young plasma from a different species, in case pigs, which means that if it were to work in humans, there would not be an issue of supply or ethical considerations. In correspondence with the researchers, I was told that they have now moved on to larger animals, specifically beagle dogs, with so far positive results, including a 50% reduction in IL-6, which they intend to publish in the coming year. This time, to further prove the cross species applicability, they have used young blood plasma from horses. In addition, they plan to test it on old cats with chronic kidney disease next year as well. If these studies are successful, the next step will be into humans. Needless to say, my fingers are crossed as I impatiently await the results!
Exosomes Break Rat Lifespan Record Full Text

In this study, it was found that an inhibitor of hyaluronan (hyaluronic acid) synthesis, 4-MU, increased the average and maximum lifespan of male mice by more than 20%. It seemed to do this by reducing blood glucose and increasing insulin sensitivity. Interestingly, the mice weighed less despite eating the same amount of food. This was a very small study, but this molecule is already in human trials, where it has recently passed phase 2a for pulmonary hypertension. I will be watching out for this molecule in the future.
Hymecromone Promotes Longevity and Insulin Sensitivity in Mice Full Text

Taking data from 7.5K US adults who wore actigraphs to measure their physical activity and were followed for seven years to assess mortality risk, it was unsurprisingly found that a greater volume and intensity of exercise was associated with reduced risk of death. However, it appears that intensity is more important than volume. Also longer continuous bouts of exercise were better than the same amount of exercise broken down into smaller chunks. There is a really nice infographic at the beginning of the article which does a good job summarizing these findings, and is worth checking out.
*Exercise Intensity, Duration, and Amount All Matter Full Text

Canadian Content Study

From McMaster University, researchers led by Bhagwati Gupta, have discovered how MANF, a protein which helps to protect neurons, plays a greater role in cell survival by regulating protein folding and clumping, as well as autophagy, the recycling system in cells. Working with c.elegans worms, those which lacked MANF had shorter survival times, while those which had more of it had 21% greater lifespan, and survived stress better. MANF is found in all animals, including us, and could play a role in healthy longevity.

From correspondence with Bhagwati, he said their current research “explores the proteins that interact with MANF to mediate its function and how secreted MANF affects different tissues and neuronal cells. We are also investigating the dynamics of MANF expression to better understand its role in cellular processes.” We wish them luck!
Protein shakeup: Researchers uncover new function of a protein that may unlock age-related illnesses Abstract Preprint Full Text

Further Canadian content is indicated by CAN

Supplemental Section

Other Areas of Interest (in alphabetical order)

Ageing Clocks & other biomarkers of ageing
*CheekAge, a next-generation epigenetic buccal clock, is predictive of mortality in human blood Full Text
*A metabolomic profile of biological aging in 250,341 individuals from the UK Biobank Full Text
*Effects of testosterone and metformin on the GlycanAge index of biological age and the composition of the IgG glycome Full Text
*There are multiple clocks that time us: Cross-sectional and longitudinal associations among 14 alternative indicators of age and aging Full Text

Blood Factors or other Heterochronic Transplantation
Hyaluronan and proteoglycan link protein 1 - a novel signaling molecule for rejuvenating aged skin Full Text
Cellular and transcriptomic changes by the supplementation of aged rat serum in human pluripotent stem cell-derived myogenic progenitors Full Text

Epigenetics & Cellular Reprogramming
Reprogramming Senescent Cells Extends Lifespan in Mice Abstract
Rejuvenating the Hippocampus With Metabolites Full Text
Neuronal Reprogramming Alleviates Alzheimer’s in Mice Full Text

Exosomes (small packets of information released by cells)
Young small extracellular vesicles rejuvenate replicative senescence by remodeling Drp1 translocation-mediated mitochondrial dynamics Full Text
Extracellular Vesicles to Fight Liver Fibrosis Full Text
Extracellular Vesicles for Treating Arthritis Full Text

Genetics including CRISPR
*Depletion of loss-of-function germline mutations in centenarians reveals longevity genes Full Text
CRISPR helps brain stem cells regain youth in mice Full Text***
Towards Fine-Tuned Control of Gene Expression Full Text

Lifespan Lengthening Interventions
Berberine extends healthspan and delays neurodegenerative diseases in Caenorhabditis elegans through ROS-dependent PMK-1/SKN-1 activation Full Text
Ageing-associated long non-coding RNA extends lifespan and reduces translation in non-dividing cells Full Text
Systems biology approaches identify metabolic signatures of dietary lifespan and healthspan across species Full Text

Microbiome
Effects of non-pharmacological interventions on gut microbiota and intestinal permeability in older adults: A systematic review: Non-pharmacological interventions on gut microbiota/barrier Full Text
Can longer lifespan be associated with gut microbiota involvement in lipid metabolism? Full Text
Impact of Mouthwash-Induced Oral Microbiome Disruption on Alzheimer's Disease Risk: A Perspective Review Full Text

Observational Studies
*Do people reach 100 by surviving, delaying, or avoiding diseases? A life course comparison of centenarians and non-centenarians from the same birth cohorts Full Text
*Delayed onset of cognitive terminal decline in later born cohorts: Evidence from a longitudinal study of two cohorts born 29-years apart
*Resilience among older adults with multimorbidity using the Connor-Davidson scale in the Canadian Longitudinal Study on Aging: health behaviour, socio-economic, and social support predictors Full Text CAN
*Cross-sectional and prospective associations between sleep health and multimorbidity in middle to older-aged adults: Results from the Canadian Longitudinal Study on Aging (CLSA) CAN
*Linking cognitive and behavioral reserve: Evidence from the CAN-PROTECT study Full Text CAN
*Younger epigenetic age is associated with higher cardiorespiratory fitness in individuals with airflow limitation Full Text CAN
*Association of Muscle Strength With All-Cause Mortality in the Oldest Old: Prospective Cohort Study From 28 Countries Full Text
*Impact of Alcohol Consumption on Lifespan: a Mendelian randomization study in Europeans Full Text

Opinion/Editorials/Theory
Defining an ageing-related pathology, disease or syndrome: International Consensus Statement Full Text
The impact of short-lived controls on the interpretation of lifespan experiments and progress in geroscience – through the lens of the “900-day rule” Preprint
*Have We Maxed Out on Life Expectancy Gains? Full Text
Five-factor theory of aging and death due to aging Full Text***
The evolution of ageing: classic theories and emerging ideas Full Text***
The Power of a Complex Systems Perspective to Elucidate Aging Full Text***

Other Ageing Biology
A New Atlas for Cellular Rejuvenation Full Text
Autodigestion From Gut Enzymes May Drive Aging Full Text
Microplastic exposure linked to accelerated aging and impaired adipogenesis in fat cells Full Text

Regenerative Medicine
Durable Muscle Extracellular Matrix Engineered with Adhesive Phenolic Moieties for Effective Skeletal Muscle Regeneration in Muscle Atrophy Full Text

Reproductive Health
Eggs from older mice regain youth when grown in young cells Abstract
New treatment extends ovarian function in older mice Abstract
*Testosterone and resistance training improved physical performance and reduced fatigue in frail older men: 1 year follow-up of a randomized clinical trial Full Text
*The association between age at natural menopause and risk of asthma among postmenopausal women from the Canadian Longitudinal Study on Aging Full Text CAN
*The Role of Curcumin in Modulating Vascular Function and Structure during Menopause: A Systematic Review Full Text
The Therapeutic Role of Genistein in Perimenopausal and Postmenopausal Women Full Text***

Reviews
Inflamm-ageing: How cytokines and nutrition shape the trajectory of ageing Full Text
Is the liver resilient to the process of ageing? Full Text
A new clinical age of aging research Full Text
Genetic and Epigenetic Alterations in Aging and Rejuvenation of Human Full Text
Longevity biotechnology: bridging AI, biomarkers, geroscience and clinical applications for healthy longevity Full Text

Senolytics/Senescent Cells
Senolytics Cocktail Dasatinib and Quercetin alleviate chondrocyte senescence and facet joint osteoarthritis in mice Full Text
A Senolytic Treatment for Liver Sepsis Full Text
Senescent cell transplantation into the skin induces age-related peripheral dysfunction and cognitive decline Full Text

Skin & Beauty
CASIN exerts anti-aging effects through RPL4 on the skin of naturally aging mice Full Text
HAPLN1 in Blood Found to Rejuvenate Skin Full Text
*The Efficacy and Safety of CollaSel Pro® Hydrolyzed Collagen Peptide Supplementation without Addons in Improving Skin Health in Adult Females Full Text
*The Effects of an Oral Supplementation of a Natural Keratin Hydrolysate on Skin Aging: A Randomized, Double-Blind, Placebo-Controlled Clinical Study in Healthy Women Full Text
*Topical Platelet Exosomes Reduce Senescence Signaling in Human Skin: An Exploratory Prospective Trial Full Text

Stem Cells
*A Bank of Centenarian Stem Cells Full Text
Rejuvenation of the reconstitution potential and reversal of myeloid bias of aged HSCs upon pH treatment Full Text
Mesenchymal Stem Cells Rejuvenate Aged Mice Full Text

Telomeres
Astragalus Supplement Lengthens Telomeres in the Middle-Aged Full Text***
Telomere stabilization by metformin mitigates the progression of atherosclerosis via the AMPK-dependent p-PGC-1α pathway Full Text
*Elevated 1-Hour Post Load Glucose as a Predictor for Telomere Attrition: a study based on a Chinese Community population Full Text

Odds & Sods
*Variety is the spice of learning, memory study suggests Full Text
*Ambient ultraviolet radiation as a cardioprotective factor: A global and regional analysis Full Text
Bats as instructive animal models for studying longevity and aging Full Text
More social species live longer, have longer generation times and longer reproductive windows Full Text

---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
***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.*
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

In a bid to finally catch up with these Longevity Reviews, I took the decision to combine the results for September and October. This led to a fair amount of hand wringing as I sought to include only the biggest and most important studies for those two months, but my final selection for the Highlights Sections sees us taking a look at the most comprehensive dietary restriction study in mice to date; how the rat lifespan record might have been broken with exosome treatment; how an inhibitor of hyaluronan synthesis increases lifespan in mice; how exercise intensity is more important than volume for mortality reduction and, in the Canadian Content Study, how a protector of neurons plays a greater role in lifespan.

As a result of this merger, the supplemental section is bigger than normal. I tried to condense it as much as possible, but there were just too many studies that had to be included. Therefore, as a brief taster, you’ll find in Lifestyle the link between cardiovascular health and cancer mortality; in Fasting, how eating late affects blood glucose; in Diet, how dietary diversity affects aging; in other Supplements, reviews of Hesperetin & NAC; in Metformin, how it slows down aging in non-human primates; in Epigenetics, reprogramming senescent cells extends mouse lifespan; in Genetics, the use of CRISPR to find new ways to rejuvenate brain stem cells; in Opinion, some new theories on aging; in Reproductive Health, how genistein can help with menopause; and finally, in Telomeres, how astragalus increased telomere length in a human trial. (To make these suggestions easier to find, I’ve marked them with ***)

NOTE: The original post was too long, so I have split the Supplemental Section in two to accomodate the limit.

Canadian Longevity Association News

The big news over the last two months is that we’ve opened up an online shop!

That’s right, just in time for Christmas, you have all your shopping needs sorted! LOL

But seriously, you can now help fund the CLA’s activities, while sporting our logo on a wide and growing range of apparel. Take a look at our shop and if there is anything missing that you’d like to purchase, then drop us a line and we’ll happily and quickly add it.

Link to the CLA’s Online Store

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.

Sep/Oct 2024 Highlights:

In the largest comparative study of different forms of dietary restriction in female mice, scientists from CALICO discovered some really interesting and puzzling results. They studied 20% and 40% caloric restriction, as well as 1 and 2 days a week fasting. The median and maximum respectively for each compared to the control were as follows: 20CR: 18% & 22%; 40CR: 36% & 38%; 1DF: 12% & 6%; 2DF: 11% & 15%.

The 40% caloric restriction mice were clearly the winners, but changes to their immune system might make them more susceptible to infection. Another big puzzle was that lower weight and fat was better in early life, but then reversed in late life. As the authors put it, “DR extends lifespan while decreasing body weight and fat mass, yet preserving body weight and fat mass is associated with longer lifespan. This paradox is a recurrent theme in this study.”

This is a really in depth and readable study, and I do recommend that you take a look at it.
Study probes how eating less can extend lifespan Full Text

A research group who have been following since they started out, and who I have covered several times in these highlights, have released their latest results. E5, a young blood plasma fraction mainly consisting of exosomes, was previously shown to reduce the epigenetic age and improve various biomarkers in rats. This new study, along with once again showing improved biomarkers and grip strength, takes it further by including lifespan. And, the result of that was that the median lifespan improved by 9.7% over controls. More tantalizingly, one of the rats potentially broke the rat lifespan record for this strain, dying at the age of 48 months, which was a 21.7% increase over the longest lived control rat!

This was a very small study, with only 8 rats in each group, however I believe this to have great potential. Especially as they used young plasma from a different species, in case pigs, which means that if it were to work in humans, there would not be an issue of supply or ethical considerations. In correspondence with the researchers, I was told that they have now moved on to larger animals, specifically beagle dogs, with so far positive results, including a 50% reduction in IL-6, which they intend to publish in the coming year. This time, to further prove the cross species applicability, they have used young blood plasma from horses. In addition, they plan to test it on old cats with chronic kidney disease next year as well. If these studies are successful, the next step will be into humans. Needless to say, my fingers are crossed as I impatiently await the results!
Exosomes Break Rat Lifespan Record Full Text

In this study, it was found that an inhibitor of hyaluronan (hyaluronic acid) synthesis, 4-MU, increased the average and maximum lifespan of male mice by more than 20%. It seemed to do this by reducing blood glucose and increasing insulin sensitivity. Interestingly, the mice weighed less despite eating the same amount of food. This was a very small study, but this molecule is already in human trials, where it has recently passed phase 2a for pulmonary hypertension. I will be watching out for this molecule in the future.
Hymecromone Promotes Longevity and Insulin Sensitivity in Mice Full Text

Taking data from 7.5K US adults who wore actigraphs to measure their physical activity and were followed for seven years to assess mortality risk, it was unsurprisingly found that a greater volume and intensity of exercise was associated with reduced risk of death. However, it appears that intensity is more important than volume. Also longer continuous bouts of exercise were better than the same amount of exercise broken down into smaller chunks. There is a really nice infographic at the beginning of the article which does a good job summarizing these findings, and is worth checking out.
*Exercise Intensity, Duration, and Amount All Matter Full Text

Canadian Content Study

From McMaster University, researchers led by Bhagwati Gupta, have discovered how MANF, a protein which helps to protect neurons, plays a greater role in cell survival by regulating protein folding and clumping, as well as autophagy, the recycling system in cells. Working with c.elegans worms, those which lacked MANF had shorter survival times, while those which had more of it had 21% greater lifespan, and survived stress better. MANF is found in all animals, including us, and could play a role in healthy longevity.

From correspondence with Bhagwati, he said their current research “explores the proteins that interact with MANF to mediate its function and how secreted MANF affects different tissues and neuronal cells. We are also investigating the dynamics of MANF expression to better understand its role in cellular processes.” We wish them luck!
Protein shakeup: Researchers uncover new function of a protein that may unlock age-related illnesses Abstract Preprint Full Text

Further Canadian content is indicated by CAN

Supplemental Section

Lifestyle
*Cardiovascular health and cancer mortality: evidence from US NHANES and UK Biobank cohort studies Full Text***
*Phenotypic age mediates effects of Life's Essential 8 on reduced mortality risk in US adults Full Text
*Optimal lifestyle patterns for delaying ageing and reducing all-cause mortality: insights from the UK Biobank Full Text
*Tree-based analysis of longevity predictors and their ten-year changes: a 35-Year mortality follow-up Full Text
*Mediterranean Diet-Based Sustainable Healthy Diet and Multicomponent Training Combined Intervention Effect on Body Composition, Anthropometry, and Physical Fitness in Healthy Aging 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.
*Associations of daily eating frequency and nighttime fasting duration with biological aging in Full Text***
*Late eating is associated with poor glucose tolerance, independent of body weight, fat mass, energy intake and diet composition in prediabetes or early onset type 2 diabetes Full Text
*The Effects of Time-Restricted Eating on Fat Loss in Adults with Overweight and Obese Depend upon the Eating Window and Intervention Strategies: A Systematic Review and Meta-Analysis Full Text

Diet – let food be thy medicine…
*Association between plant and animal protein and biological aging: findings from the UK Biobank Full Text
*Intake of vegetables and fruits at midlife and the risk of physical frailty in later life Full Text
*A reduced carbohydrate diet improves glycemic regulation in hyperglycemic older people in a retirement home: The SAGE study CAN
*Dietary Diversity Is Associated With Delayed Aging Full Text***

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*Optimal dose and type of exercise to improve cognitive function in patients with mild cognitive impairment: a systematic review and network meta-analysis of RCTs Full Text
*Hydrolyzed collagen supplementation prior to resistance exercise augments collagen synthesis in a dose-response manner in resistance-trained, middle-aged men
*Does Taking a Break Matter—Adaptations in Muscle Strength and Size Between Continuous and Periodic Resistance Training 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 improves assisted reproductive technology outcomes in poor ovarian responders through alleviating oxidative stress, inflammation, and apoptosis: a randomized clinical trial Full Text
*Astaxanthin compound nutrient improved insulin resistance, hormone levels, embryo quality and pregnancy outcomes in polycystic ovary syndrome patients undergoing in vitro fertilization/intracytoplasmic sperm injection 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 effect of curcumin supplementation on glycemic indices in adults: A meta-analysis of meta-analyses
*The effect of curcumin supplementation on endothelial function and blood pressure in patients with metabolic disorders: A meta-analysis of meta-analyses
*Curcumin extract improves beta cell functions in obese patients with type 2 diabetes: a randomized controlled trial Full Text

Fisetin
Fisetin as a Senotherapeutic Agent: Evidence and Perspectives for Age-Related Diseases Full Text

Melatonin
Dysfunctional mitochondria in age-related neurodegeneration: Utility of melatonin as an antioxidant treatment Full Text
Unlocking the health benefits of melatonin supplementation: A promising preventative and therapeutic strategy Full Text

Nicotinamide MonoNucleotide (NMN)
Nicotinamide mononucleotide supplementation rescues mitochondrial and energy metabolism functions and ameliorates inflammatory states in the ovaries of aging mice Full Text
Research advances in the function and anti-aging effects of nicotinamide mononucleotide Full Text
*The versatile multi-functional substance NMN: its unique characteristics, metabolic properties, pharmacodynamic effects, clinical trials, and diverse applications Full Text

Nicotinamide Riboside (NR)
NAD+ depletion is central to placental dysfunction in an inflammatory subclass of preeclampsia Full Text CAN

Pterostilbene
From Nature to Treatment: The Impact of Pterostilbene on Mitigating Retinal Ischemia–Reperfusion Damage by Reducing Oxidative Stress, Inflammation, and Apoptosis Full Text
Exploration of Nutraceutical Potentials of Isorhapontigenin, Oxyresveratrol and Pterostilbene: A Metabolomic Approach Full Text

Resveratrol
Resveratrol as a potential therapeutic agent for sarcopenic obesity: Insights from in vivoperiments Full Text
Resveratrol delays the progression of diabetic nephropathy through multiple pathways: A dose–response meta-analysis based on animal models Full Text
The role and current research status of resveratrol in the treatment of osteoarthritis and its mechanisms: a narrative review Full Text

Spermidine
The longevity factor spermidine is part of a highly heritable complex erythrocyte phenotype associated with longevity Full Text

Other available supplements or natural substances (in alphabetical order)
*Efficacy of Berberis vulgaris and Berberis integerrima on glycemic indices and weight profile in type 2 diabetic patients: A systematic review and meta-analysis of randomized controlled trials Full Text
*Blueberry Extract Aids Cognition in People With Inflammation Full Text
The impact of cysteine on lifespan in three model organisms: A systematic review and meta-analysis Full Text
Comprehensive review of Hesperetin: Advancements in pharmacokinetics, pharmacological effects, and novel formulations Full Text***
*N-acetylcysteine Clinical Applications Full Text***
*Dose–response relationship of dietary Omega-3 fatty acids on slowing phenotypic age acceleration: a cross-sectional study Full Text
Royal jelly a promising therapeutic intervention and functional food supplement: A systematic review Full Text

Combinations
Plant extracts and omega-3 improve short-term memory and modulate the microbiota-gut-brain axis in D-Galactose model mice Full Text
Plant extracts and omega-3 supplementation modulate hippocampal oxylipin profile in response to LPS-induced neuroinflammation Full Text
The Combined Effect of Green Tea, Saffron, Resveratrol, and Citicoline against Neurodegeneration Induced by Oxidative Stress in an In Vitro Model of Cognitive Decline Full Text

Prescription Supplements

Metformin
The brain aged more slowly in monkeys given a cheap diabetes drug
Metformin Slows Aging in Non-Human Primates Abstract ***
*Metformin Exhibits Anti-Inflammatory Effects by Regulating microRNA-451/CXCL16 and B Cell Leukemia/Lymphoma 2 in Patients With Osteoarthritis Full Text
Metformin: Beyond Type 2 Diabetes Mellitus Full Text

Rapamycin (sirolimus)
Calorie restriction and rapamycin distinctly restore non-canonical ORF translation in the muscles of aging mice Full Text
Rapamycin Treatment Reduces Brain Pericyte Constriction in Ischemic Stroke Full Text
*A single-center, double-blind, randomized, placebo-controlled, two-arm study to evaluate the safety and efficacy of once-weekly sirolimus (rapamycin) on muscle strength and endurance in older adults following a 13-week exercise program Full Text

Miscellaneous Molecules & Prescription Drugs
*Effect of frailty on effectiveness and safety of GLP-1 receptor agonists versus SGLT2 inhibitors in people with type 2 diabetes in Taiwan: a retrospective, nationwide, longitudinal study Full Text
Expanding access to weight-loss drugs could save thousands of lives a year Full Text
*Association between statin usage and mortality outcomes in aging U.S. cancer survivors: a nationwide cohort study Full Text
*Association between prescription drugs and all-cause mortality risk in the UK population Full Text

Novel Molecules
Blocking a Dopamine Receptor May Improve Memory Full Text
NX210c drug candidate peptide strengthens mouse and human blood-brain barriers Full Text

---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
***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.*
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

Hello again! I’m returning after a health related absence, so this review has taken a lot longer to get finished - trying now desperately to get back on track! I might combine the next two months into one so that I’ll have caught up.

August was highlighted by the results of the first human rapamycin study devoted to longevity; the synthesis of a novel autophagy activator which increased mouse lifespan; the improvement of aging in rats with MSC treatment; a review of combination treatments in mice; a look at the 11th Aging Research & Drug Discovery meeting; and for the Canadian content study, the discovery of a new DNA repair mechanism.

In the Supplemental Section, you’ll find in NMN, a couple of systematic reviews of human trials to date; in Other Supplements, how taking creatine can help with sleep on training days; in Combinations, how mTOR and SGLT-2 inhibitors could be synergistic; in Exosomes, how ultrasound preconditioned exosomes help with rotator cuff regeneration; in Genetics, how regenerative genes improves lifespan across the species barrier; in Observational Studies, how there are two distinct periods where rapid aging occurs; in Reproductive Health, how users of hormone therapy are biologically younger; and in Skin & Beauty, a review of Coenzyme Q10 for skiing aging. (To make these suggestions easier to find, I’ve marked them with ***)

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.

August 2024 Highlights:

I’m delighted to bring you the results of the very first rapamycin trial designed from the outset to investigate longevity. I’m especially excited as I was involved in the crowdfunding campaign, helping to write the campaign page and being one of the donors. The trial lasted for 48 weeks and featured 114 participants which took either 5mg, 10mg of rapamycin or a placebo once a week.

Although aimed at longevity as the target, this trial was still primarily a safety trial, hoping to get as many learnings as possible for subsequent larger trials. Unfortunately, the biggest learning was that the compounded form of rapamycin used was only 28% as bioavailable as the generic version, so that the 5mg and 10mg doses translated to roughly 1.4mg and 2.9mg respectively. The authors only found this out once the trial was underway and is the subject of the first paper shown below.

The most important result was that weekly low dose rapamycin was safe to take for a large number of people with minimal side effects, in fact, any minor side effects were similar to placebo. As for changes caused by rapamycin, “Lean tissue mass and self-reported pain improved significantly for women using 10mg rapamycin. Trends of improvement in bone mineral density were observed in males using 10mg rapamycin, but no other significant effects were observed.”

Although I had hoped that there would be more significant effects, it is not particularly surprising considering the reduced doses, and fortunately there were still effects at those doses. The authors will take the learnings and apply them to subsequent larger and longer lasting trials. In addition, this is only the first paper, with other parameters still to be reported on. Note: this study is still a pre-print, so it has yet to be peer reviewed.
*The bioavailability of compounded and generic rapamycin in normative aging individuals: A retrospective study and review with clinical implications Full Text
*Safety and efficacy of rapamycin on healthspan metrics after one year: PEARL Trial Results Full Text

Here, researchers synthesised a novel autophagy (a recycling mechanism in our cells) activator, CXM102, which rejuvenated bone marrow stem cells. This resulted in increased bone growth, and less bone loss in middle aged mice. In addition, inflammation and organ fibrosis was decreased. Most noteworthy, CXM102 treatment led to increased lifespan, which surpassed that of rapamycin, which acted as a positive control (though the number of animals was so small that it could just be statistical noise). Very interested to see larger lifespan studies carried out on this new molecule.
Rejuvenation of BMSCs senescence by pharmacological enhancement of TFEB-mediated autophagy alleviates aged-related bone loss and extends lifespan in middle aged mice Full Text

In this study researchers thoroughly tested the anti-aging effects of human derived umbilical Mesenchymal Stromal Cells (MSCs), a form of stem cells, in older rats. The MSCs turned out to reduce oxidative stress, repair tissue, regulate metabolism and improve immune functions across multiple organs. They also altered the microbiota towards a more youthful state. Altogether showing that MSCs “concurrently regulate multiple aging processes and improve a range of aging phenotypes”, “thus presenting a promising anti-aging therapeutic approach.”
MSC Treatment Improves Age-Related Phenotypes in Rats Full Text

I normally don’t include reviews in the Highlights section, but when that review is of all the combination studies done in mice for longevity, I make an exception! If you’ve read these reviews before, you’ll know that I continually emphasise that effective longevity treatments are going to require multiple avenues of attack as aging is such a multifaceted problem.

This review is a great resource, as it lists each of the interventions, gives the primary hallmark of aging it targets as well as giving the percentage of lifespan increase. Well worth your perusal.
Combining Treatments Against Multiple Hallmarks of Aging Full Text

Finishing off with another longevity conference, this time with the biggest and most important of them all - the Aging Research and Drug Discovery meeting (ARDD), held in Copenhagen at the end of every summer. This year was the biggest ever, with more than 160 talks, and you can read about in this write up by Arkadi Mazin of Lifespan.io:
For the 11th Year in Copenhagen: Highlights from ARDD 2024 ARDD Website
In addition, most of the talks are recorded and are uploaded to the meeting’s YouTube channel. ARDD YouTube Channel

Canadian Content Study

From Western University, first author Robert Szabla and his group have discovered a new DNA repair mechanism in the bacterium Deinococcus Radiodurans, which is one of the hardiest organisms, being able to withstand huge amounts of radiation. The mechanism consists of a single protein, DdrC, which scans DNA, and then snaps shut like a mousetrap when it detects damage, alerting the cell to then fix that damage. Equally excitingly, they were able to transfer this protein to another single celled organism, making it much more resistant to DNA damage.

This could in theory be applied to human cells as well, which is a direction the research team will be moving in, as shared to me by Robert that “we will be exploring whether exogenous DdrC can improve DNA damage resistance in human cells”. Watch this space!
Newly discovered protein stops DNA damage Full Text Brief YouTube Video

Further Canadian content is indicated by CAN

Supplemental Section

Lifestyle
*A healthy lifestyle may counteract diabetes-associated brain aging Full Text
*Association between Life's Essential 8 and cognitive function among older adults in the United States Full Text

Fasting/Dietary Restriction – certainly the cheapest & also one of the most effective anti-ageing interventions currently available.
Spermidine is essential for fasting-mediated autophagy and longevity Full Text
Fasting and calorie restriction modulate age-associated immunosenescence and inflammaging Full Text

Diet – let food be thy medicine…
*Anti-Inflammatory Diets Mitigate Risk of Dementia Full Text
*Red and processed meat consumption associated with higher type 2 diabetes risk, study of two million people finds Full Text
*Dietary trajectories over 21 years and frailty in Norwegian older adults: the Tromsø Study 1994–2016 Full Text
*Plant but not animal sourced nitrate intake is associated with lower dementia-related mortality in the Australian Diabetes, Obesity, and Lifestyle Study Full Text
*Alcohol Consumption Patterns and Mortality Among Older Adults With Health-Related or Socioeconomic Risk Factors Full Text

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*Associations Between Professional Sports and Longevity Full Text
*Weekend-Oriented Physical Activity Superior for Brain Health Abstract

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.
*The effect of astaxanthin after varicocele surgery on antioxidant status and semen quality in infertile men: A triple-blind randomized clinical trial Full Text
*Exploring the Impact of Astaxanthin Supplementation in Conjunction with a 12-Week CrossFit Training Regimen on Selected Adipo-Myokines Levels in Obese Males 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: A Golden Approach to Healthy Aging: A Systematic Review of the Evidence Full Text
Curcumin and Cognitive Function: A Systematic Review of the Effects of Curcumin on Adults With and Without Neurocognitive Disorders Full Text

Ketones
*Daily consumption of ketone ester, bis-octanoyl ®-1,3-butanediol, is safe and tolerable in healthy older adults in a randomized, parallel arm, double-blind, placebo-controlled, pilot study Full Text
A Ketosis-Related Compound Alleviates Arthritis in Rats Full Text

Nicotinamide MonoNucleotide (NMN)
*Efficacy of oral nicotinamide mononucleotide supplementation on glucose and lipid metabolism for adults: a systematic review with meta-analysis on randomized controlled trials Full Text***
*Improved Physical Performance Parameters in Patients Taking Nicotinamide Mononucleotide (NMN): A Systematic Review of Randomized Control Trials Full Text***

Nicotinamide Riboside (NR)
Nicotinamide riboside modulates the reactive species interactome, bioenergetic status and proteomic landscape in a brain-region-specific manner Full Text

Pterostilbene
Effects of Pterostilbene on Cardiovascular Health and Disease Full Text

Resveratrol
*Oral resveratrol in adults with knee osteoarthritis: A randomized placebo-controlled trial (ARTHROL) Full Text

Spermidine
A surge in endogenous spermidine is essential for rapamycin-induced autophagy and longevity Full Text
*Non-Linear Association of Dietary Polyamines with the Risk of Incident Dementia: Results from Population-Based Cohort of the UK Biobank Full Text

Other available supplements or natural substances (in alphabetical order)
*Vitamin B12 status and skeletal muscle function among elderly: A literature review and pilot study on the effect of oral vitamin B12 supplementation in improving muscle function Full Text
The impact of carnosine on biological ageing – A geroscience approach Full Text
*Creatine Improves Total Sleep Duration Following Resistance Training Days versus Non-Resistance Training Days among Naturally Menstruating Females Full Text***
*Comparison of functional performance outcomes between oral patented crystalline glucosamine sulfate and platelet-rich plasma among knee osteoarthritis patients: a propensity score matching analysis Full Text
Effects of Ginger (Zingiber officinale) on the Hallmarks of Aging Full Text
*ω-3 PUFA for Secondary Prevention of White Matter Lesions and Neuronal Integrity Breakdown in Older Adults Full Text
Omega-3 PUFAs slow organ aging through promoting energy metabolism Full Text
Rosemary extract activates oligodendrogenesis genes in mouse brain and improves learning and memory ability Full Text
Mitigation of aging-related plasticity decline through taurine supplementation and environmental enrichment Full Text
Bidirectional Effect of Long-Term Δ9-Tetrahydrocannabinol Treatment on mTOR Activity and Metabolome Full Text

Combinations
mTOR and SGLT-2 Inhibitors Impact Age-Related Processes Full Text***
*A Randomised, Double-Blind, Placebo-Controlled, Cross-Over Clinical Trial to Evaluate the Biological Effects and Safety of a Polyphenol Supplement on Healthy Ageing Full Text
Synergistic anti-aging effect of Dendrobium officinale polysaccharide and spermidine: A metabolomics analysis focusing on the regulation of lipid, nucleotide and energy metabolism
*Functional and metabolic effects of omega-3 polyunsaturated fatty acid supplementation and the role of β-hydroxy-β-methylbutyrate addition in chronic obstructive pulmonary disease: A randomized clinical trial Full Text

Prescription Supplements

Metformin
Metformin: From diabetes to cancer to prolongation of life Full Text

Rapamycin (sirolimus)
Calorie restriction and rapamycin distinctly mitigate aging-associated protein phosphorylation changes in mouse muscles Full Text
Rapamycin Attenuates H2O2-Induced Oxidative Stress-Related Senescence in Human Skin Fibroblasts

Miscellaneous Molecules & Prescription Drugs
GDF11 protects against mitochondrial-dysfunction-dependent NLRP3 inflammasome activation to attenuate osteoarthritis Full Text
*Comparative renal outcomes of matched cohorts of patients with type 2 diabetes receiving SGLT2 inhibitors or GLP-1 receptor agonists under routine care Full Text

Other Areas of Interest (in alphabetical order)

Ageing Clocks & other biomarkers of ageing
*Proteomic aging clock predicts mortality and risk of common age-related diseases in diverse populations Full Tex
New Epigenetic Clock Built on Lurking DNA Fragments Full Text
*A systematic review of phenotypic and epigenetic clocks used for aging and mortality quantification in humans Full Text

Blood Factors or other Heterochronic Transplantation
Aging insights from heterochronic parabiosis models Full Text

Epigenetics & Cellular Reprogramming
Some Cells Age Much Faster Than Others Full Text

Exosomes (small packets of information released by cells)
Engineered exosome therapeutics for neurodegenerative diseases Full Text
Exosomes derived from bone marrow mesenchymal stem cell preconditioned by low-intensity pulsed ultrasound stimulation promote bone–tendon interface fibrocartilage regeneration and ameliorate rotator cuff fatty infiltration Full Text***
Exploring senescence as a modifier of β cell extracellular vesicles in type 1 diabetes Full Text CAN

Genetics including CRISPR
Highly regenerative species-specific genes improve age-associated features in the adult Drosophila midgut Full Text***

Lifespan Lengthening Interventions
Heat-killed probiotic Levilactobacillus brevis MKAK9 and its exopolysaccharide promote longevity by modulating aging hallmarks and enhancing immune responses in Caenorhabditis elegans Full Text
Newly discovered gene may influence longevity Full Text
Characterization of effects of mTOR inhibitors on aging in C. elegans Full Text

Microbiome
Association between Accelerated Biological Aging, Diet, and Gut Microbiome Full Text
The Role of Akkermansia muciniphila on Improving Gut and Metabolic Health Modulation: A Meta-Analysis of Preclinical Mouse Model Studies Full Text

Observational Studies
*Association between weight change and serum anti-aging protein α-Klotho: a cross-sectional study in middle-aged and older adults Full Text
*Nonlinear dynamics of multi-omics profiles during human aging Full Text***
*Individual socioeconomic status, neighborhood disadvantage, and cognitive aging: A longitudinal analysis of the CLSA Full Text CAN
*The association between trajectories of marital status and successful aging varies by sex: Findings from the Canadian Longitudinal Study on Aging (CLSA) Full Text CAN

Opinion/Editorials/Theory
Inflated expectations: the strange craze for translational research on aging: Given existing confusion about the basic science of aging, why the high optimism in the private sector about the prospects of developing anti-aging treatments? Full Text
Enhanced cellular longevity arising from environmental fluctuations Full Text

Other Ageing Biology
Cleaning up the aging brain: Scientists restore brain's trash disposal system Cleaning up the aging brain Abstract
*Inflammation May Drive Fat Distribution in Older People Full Text
Why Bone Destruction Is Accelerated with Aging Full Text

Reproductive Health
*Hormone Therapy and Biological Aging in Postmenopausal Women Full Text***
A scoping review regarding reproductive capacity modulation based on alpha-ketoglutarate supplementation Full Text
*Effect of astaxanthin supplementation on female fertility and reproductive outcomes: a systematic review and meta-analysis of clinical and animal studies Full Text

Reviews
Precision epigenetic editing: Technological advances, enduring challenges, and therapeutic applications Full Text
Recent advances in Alzheimer’s disease: Mechanisms, clinical trials and new drug development strategies Full Text
Anti-ageing interventions for the treatment of cardiovascular disease Full Text
Advances in targeted therapies for age-related osteoarthritis: A comprehensive review of current research Full Text

Senolytics/Senescent Cells
Senolytic intervention improves cognition, metabolism, and adiposity in female APPNL−F/NL−F mice Full Text
Glutaminase-1 inhibition alleviates senescence of Wharton’s jelly-derived mesenchymal stem cells via senolysis Full Text
Intermittent clearance of p21-highly-expressing cells extends lifespan and confers sustained benefits to health and physical function

Skin & Beauty
The Role of Coenzyme Q10 in Skin Aging and Opportunities for Topical Intervention: A Review Full Text***
*Influence of collagen peptide supplementation on visible signs of skin and nail health and -aging in an East Asian population Full Text
*Cosmeceuticals: A Review of Clinical Studies Claiming to Contain Specific, Well-Characterized Strains of Probiotics or Postbiotics Full Text
How Supplement Formulas, Including NOVOS, Affect Skin Aging Full Text

Telomeres
The Impact of the Mediterranean Diet on Telomere Biology: Implications for Disease Management—A Narrative 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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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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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.

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.

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.

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

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.
*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

Odds & Sods
Cannabinoids and healthy ageing: the potential for extending healthspan and lifespan in preclinical models with an emphasis on Caenorhabditis elegans Full Text
Hyperbaric Oxygen Therapy Reduces the Traumatic Brain Injury–Mediated Neuroinflammation Through Enrichment of Prevotella Copri in the Gut of Male Rats Full Text
Hyperbaric oxygen therapy: future prospects in regenerative therapy and anti-aging Full Text
Hyperbaric Oxygen Improves Long-Term Learning and Memory Impairment by Attenuating Neuronal Apoptosis in aMCI Rats 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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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!

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.

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

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 prevents bone loss in osteoporotic rats with palmitic acid through suppressing oxidative stress Full Text
Nrf2 Plays a Key Role in Erythropoiesis during Aging 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.***

**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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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:

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

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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.

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

Are age-related neurodegenerative diseases caused by a lack of the diet-derived compound ergothioneine? 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

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.
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