LONGECITY Blogs RSS feed Last Updated: 30 April 2025 - 09:12 AM

As the flowers are finally starting to bloom in my garden, we will take a look at an intriguing study which uses ultrasound to reverse cellular senescence and increase mouse lifespan; two studies on reducing lower back pain, the first using epigenetic reprogramming, while the second is a Canadian study using senolytics; and, a fascinating study where an induced torpor like state (akin to hibernation) improves healthspan.

In the Supplemental Section, you’ll find in Lifestyle a couple of studies on the importance of sleep for mortality and stroke risk; in Diet, a Canadian study on optimal dietary patterns for healthy aging; in Exercise, how any form of exercise can boost brain function; in Other Supplements, how citrulline can help with aging; in Combinations, the results of human trials on two commercial supplement stacks; and, in Blood Factors, how giving blood could give yourself health benefits. Plus of course much more! (To make these suggestions easier to find, I’ve marked them with ***)

PUBLISHING NOTE: It is with a heavy heart that I have to let you know that these newsletters will be switching to bi-monthly, or every second month from now on. I’ve been producing them monthly since the beginning of 2019, with the accompanying videos starting in 2022, and have always put my soul into them. They marked my first foray into longevity advocacy and ultimately led to the founding of the CLA. However, they take an immense amount of time to put together, and in the past couple of years have been getting in the way of my CLA work. Despite various attempts to rearrange my schedule and to be more productive, it has proven to be impossible to drastically reduce the amount of time devoted to them without taking this step. But, it should result in much faster progress with the CLA. I hope for your understanding.

Canadian Longevity Association News

Apart from having done our taxes for 2024, getting corporate credit and debit cards, and starting to post on Bluesky, the major news is that the CLA is finally getting representation on the west coast, with the onboarding of our latest volunteer - a warm welcome to Stephen! The CLA is looking to get representatives in every province and territory, as most of healthcare is implemented at the provincial level and a large part of our advocacy efforts must also be tailored to that level. Get in touch if you would be interested in becoming a CLA representative where you live.

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 TikTok Bluesky

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.

March 2025 Highlights:

This study really caught my attention as it suggests that low frequency ultrasound could be a longevity treatment of the future. In this study, researchers were able to reverse cellular senescence and increase the lifespan of mice, as well as improving their appearance and movement. Animals were placed in a water bath and treated with ultrasound at a specific frequency for 30 minutes at varying doses and schedules. Animals given lower doses (every second or third day) saw the biggest improvement in lifespan. You can watch brief videos of the differences between the treated and control mice inside the paper or in my review. Looking ahead, if these results are replicated and considering how many millions of people worldwide have safely had ultrasounds, I can imagine this swiftly moving into human studies.
Rejuvenation of Senescent Cells, In Vitro and In Vivo, by Low-Frequency Ultrasound Full Text
CLA Video Review

Additional study from March showing benefits of ultrasound for senescence:
Low-intensity pulsed ultrasound inhibits chondrocyte senescence by inhibiting PI3K/AKT/mTOR signaling Full Text

Lower back pain is one of the most common chronic conditions of aging, affecting more than 80% of us at some point in our lives. It is mainly caused by intervertebral disk degeneration (IVDD) and is a leading cause of disability and loss of quality of life. Although symptoms can be reduced, there is no cure. However, that could change in the future as shown by the first of two highlighted studies into reducing lower back pain. Here, researchers used epigenetic reprogramming to reduce markers of senescence and reverse degeneration in rats, as well as reduce certain measures of pain. This is still very early days, but this is another study highlighting the potential power epigenetic reprogramming.
Reprogramming Epigenetics to Fight Back Pain Full Text CLA Video Review

In this fascinating study, researchers were able to induce a torpor-like state, which is similar to hibernation, in mice. This led to a decreased metabolic rate and lowered body temperature, which resulted in a slowing down of epigenetic aging across multiple tissues and improved healthspan. It will be interesting to see if these results end up leading to any future treatments.
A torpor-like state in mice slows blood epigenetic aging and prolongs healthspan Full Text
No video review for this one - sorry!

Canadian Content Study

Coming out of the lab of Lisbet Haglund of McGill University, our second highlighted study for reducing lower back pain uses the senolytics o-vanillin and RG-7112 to remove senescent cells from the spine and improve lower back pain in a mouse model of early IVDD. The combination of the two senolytics worked better than either alone.

Haglund’s lab is currently working on a study to see if the same senolytics can prevent back pain from occurring in the first place, as well as prevent bone loss in a separate study in wild-type mice. They are also optimising o-vanillin’s pharmacokinetic properties. Hopefully all this work will eventually result in some human clinical trials!
Senolytics Decrease Low Back Pain in Mice Full Text CLA Video Review
Further Canadian content is indicated by CAN

Supplemental Section

Lifestyle
*Healthy lifestyle habits, educational attainment, and the risk of 45 age-related health and mortality outcomes in the UK: A prospective cohort study Full Text
*Imbalanced sleep increases mortality risk by 14–34%: a meta-analysis Full Text***
*Inadequate sleep increases stroke risk: evidence from a comprehensive meta-analysis of incidence and mortality Full Text***

Fasting/Dietary Restriction
Intermittent fasting boosts sexual behavior by limiting the central availability of tryptophan and serotonin Full Text
*Relationship between dietary energy and macronutrient intake at dinner versus breakfast and biological aging and premature mortality: Assessment of 2003–2014 National Health and Nutrition Examination Survey participants
Time restricted feeding with or without ketosis influences metabolism-related gene expression in a tissue-specific manner in aged rats Full Text

Diet
*Huge Diet Study: More Butter, More Problems Full Text
*Dietary Patterns Associated With Healthy Aging Full Text*** CAN
*Almond snacking modulates gut microbiome and metabolome in association with improved cardiometabolic and inflammatory markers Full Text
*The effects of wine consumption and lipid profile: A systematic review and meta-analysis of clinical trials Full Text

Exercise
*Age-Related Differences in Adaptation of Lean Body Mass, Muscle Strength, and Performance Following 6 Weeks of Blood Flow Restriction Training in Young and Older Adults Full Text CAN
*Exercise of any kind boosts brainpower at any age Full Text***
*Sex-specific effects of intensity and dose of physical activity on BOLD-fMRI cerebrovascular reactivity and cerebral pulsatility Full Text CAN
*Impact of combined high-intensity bodyweight interval training and breathing exercise on cardiometabolic health in normal-weight middle-aged adults with hypertension Full Text

Non-prescription Supplements (in alphabetical order)

Curcumin
*An Umbrella Review of Systematic Reviews and Meta-analyses of Randomized Controlled Trials Investigating the Effect of Curcumin Supplementation on Lipid Profiles Full Text
*Impacts of Curcumin Supplementation on Cardiometabolic Risk Factors in Patients With Polycystic Ovary Syndrome: A Systematic Review and Dose−Response Analysis Full Text
Impact of curcumin on gut microbiome Full Text

Fisetin
Combination Therapy of Losartan and Fisetin Reduces Senescence and Enhances Osteogenesis in Human Bone Marrow–Derived Mesenchymal Stem Cells Full Text

Resveratrol
*Resveratrol Upregulates Antioxidant Factors Expression and Downmodulates Interferon-Inducible Antiviral Factors in Aging Full Text
*Microbiota-derived resveratrol metabolites: New biomarkers of red wine consumption are inversely associated with inflammation in a longitudinal study of a Mediterranean population Full Text
*Impact of Resveratrol Supplementation on Human Sirt1: A GRADE-Assessed Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials (RCTs) Full Text

Other available supplements or natural substances (in alphabetical order)
Carotenoids for Antiaging: Nutraceutical, Pharmaceutical, and Cosmeceutical Applications Full Text
Citrulline regulates macrophage metabolism and inflammation to counter aging in mice Full Text***
*Unveiling the geroprotective potential of Monarda didyma L.: insights from in vitro studies and a randomized clinical trial on slowing biological aging and improving quality of life Full Text
*Nicotinic acid increases adipose tissue dietary fatty acid trapping and reduces postprandial hepatic and cardiac fatty acid uptake in prediabetes Full Text CAN
*Effect of 12-week dietary nitrate supplementation on carotid arterial stiffness in postmenopausal females Full Text
*BEETter AGING: Short-Term Dietary Nitrate Supplementation Enhances Muscle Contractile Properties in Older But Not in Young Adult
*Increasing nitric oxide availability via ingestion of nitrate-rich beetroot juice improves vascular responsiveness in individuals with Alzheimer’s Disease. Full Text
*Systemic immune inflammation mediates the association of serum omega-3 and omega-6 polyunsaturated fatty acids with biological aging: a national population-based study Full Text
*Elevated urinary phytoestrogens are associated with delayed biological aging: a cross-sectional analysis of NHANES data Full Text

Combinations
*Effects of vitamin D3, omega-3 fatty acids and a simple home exercise program on change in physical activity among generally healthy and active older adults: The 3-year DO-HEALTH trial Full Text
Assessment of the Capability of Mesenchymal Stem Cells and/or Pyrroloquinoline Quinone in Compensating the Age-Related Dysfunctions of AMP-Activated Protein Kinase Pathway in Wistar Rats
*The efficacy of Sarcomeal® oral supplementation plus vitamin D3 on muscle parameters, metabolic factors, and quality of life in diabetic sarcopenia: a randomized controlled clinical trial Full Text
*Effects of a natural ingredients-based intervention targeting the hallmarks of aging on epigenetic clocks, physical function, and body composition: a single-arm clinical trial Full Text***
*Enhancement of NK Cell Cytotoxic Activity and Immunoregulatory Effects of a Natural Product Supplement Across a Wide Age Span: A 30-Day In Vivo Human Study Full Text***
Nicotinamide mononucleotide combined with PJ-34 protects microglial cells from lipopolysaccharide-induced mitochondrial impairment through NMNAT3-PARP1 axis Full Text

Prescription Supplements

Metformin
*Metformin and physical performance in older people with probable sarcopenia and physical prefrailty or frailty in England (MET-PREVENT): a double-blind, randomised, placebo-controlled trial Full Text
Metformin's Anticancer Odyssey: Revealing Multifaceted Mechanisms Across Diverse Neoplastic Terrains- A Critical Review Full Text
Opposite causal effects of type 2 diabetes and metformin on Alzheimer's disease Full Text

Rapamycin (sirolimus)
Ovarian cryopreservation with rapamycin improves fertility restoration in a murine orthotopic transplantation model Full Text
mTOR Inhibition limits LPS induced acute kidney injury and ameliorates hallmarks of cellular senescence Full Text
*Rapamycin enhances neurovascular, peripheral metabolic, and immune function in cognitively normal, middle-aged APOE4 Carriers: genotype-dependent effects compared to non-carriers Full Text PREPRINT

Miscellaneous Molecules & Prescription Drugs
*Impact of Disease-Modifying Antirheumatic Drugs on Cognitive Function in Older Adults with Rheumatoid Arthritis Full Text
*Sildenafil and risk of Alzheimer disease: a systematic review and meta-analysis Full Text
Neuroprotective effects of SGLT2 inhibitors empagliflozin and dapagliflozin on Aβ1–42-induced neurotoxicity and neuroinflammation in cellular models of Alzheimer's disease CAN

Novel Molecules
Elamipretide, a Potential New Drug, Reduces Frailty in Mice Full Text
3-Monothiopomalidomide, a new immunomodulatory imide drug (IMiD), blunts inflammation and mitigates ischemic stroke in the rat Full Text

Other Areas of Interest (in alphabetical order)

Ageing Clocks
*Chemical and Climatic Environmental Exposures and Epigenetic Aging: a Systematic Review Full Text
*Epigenetic Clocks Relate to Four Age-Related Health Outcomes Similarly across Three Countries Full Text
*Epigenetic age acceleration and mortality risk prediction in US adults Full Text

Blood Factors or other Heterochronic Transplantation
*Beneficial genetic changes observed in regular blood donors Full Text***

Epigenetics & Cellular Reprogramming
Conserved Biological Processes in Partial Cellular Reprogramming: Relevance to Aging and Rejuvenation Full Text
Epigenetic editing at individual age-associated CpGs affects the genome-wide epigenetic aging landscape Full Text

Exosomes (small packets of information released by cells)
Heme oxygenase 1‑overexpressing bone marrow mesenchymal stem cell‑derived exosomes suppress interleukin‑1 beta‑induced apoptosis and aging of nucleus pulposus cells Full Text
Extracellular Vesicles Restore Some Heart Function to Mice Full Text
Exosomal miR-499a-5p from human umbilical cord mesenchymal stem cells attenuates liver fibrosis via targeting ETS1/GPX4-mediated ferroptosis in hepatic stellate cells Full Text

Genetics including CRISPR
Genetically supported targets and drug repurposing for brain aging: A systematic study in the UK Biobank Full Text
Bcl-xL overexpression in T cells preserves muscle mitochondrial structure and function and prevents frailty in old mice Full Text
Beneficial effects of vascular endothelial growth factor B gene transfer in the aged heart Full Text

Lifespan Lengthening Interventions
High-content screening identifies ganoderic acid A as a senotherapeutic to prevent cellular senescence and extend healthspan in preclinical models Full Text
The Impact of Rosemary and Ginger Extracts on Aging and Healthspan in Drosophila Full Text
Association of α-Klotho with anti-Aging effects of Ganoderma lucidum in animal models
Chrysophanol delays aging via insulin/IGF-1 signaling pathway
β-hydroxy-β-methylbutyrate Attenuates Age-Dependent Loss of Flight Ability and Extends Lifespan in Drosophila Full Text

Microbiome
*Assessing the gut microbiota composition in older adults: connections to physical activity and healthy ageing Full Text
*The association between gut microbiota and accelerated aging and frailty: a Mendelian randomization study Full Text
Streptococcus thermophilus CNCM I-5570 lysate counteracts the aging process in human dermal fibroblast cells by neutralizing harmful free radicals and impacting antioxidant and anti-inflammatory pathways, thus restoring their physiological functions Full Text

Observational Studies
*Caregiving is Associated with Lower Brain Age in Humans Full Text
*BMI-for-age percentile curves for older adults Full Text CAN
*Personality Traits and Health Behaviors as Predictors of Fall Among Community-Dwelling Older Adults: Findings From the Canadian Longitudinal Study on Aging Full Text CAN
*Satisfaction with Life of Older Men and Women in the Canadian Longitudinal Study on Aging (CLSA) and its Association with Formal and Informal Home Care Full Text CAN

Opinion/Editorials/Theory/Policy
What Comes Next for Vitamin D Supplementation and Trials in Older Adults? Full Text
The ongoing challenge of slowing aging through drug discovery Full Text

Other Ageing Biology
Nicotinamide riboside and nicotinamide mononucleotide facilitate NAD+ synthesis via enterohepatic circulation Full Text
Drug-Based Lifespan Extension in Mice Strongly Affects Lipids Across Six Organs Full Text
A stress-dependent TDP-43 SUMOylation program preserves neuronal function Full Text CAN

Regenerative Medicine
Endodontic Regeneration Therapy: Current Strategies and Tissue Engineering Solutions Full Text

Reproductive Health
*Menopausal symptom burden as a predictor of mid- to late-life cognitive function and mild behavioral impairment symptoms: A CAN-PROTECT study Full Text CAN
*Semen quality and lifespan: a study of 78 284 men followed for up to 50 years Full Text
BDNF secreted by mesenchymal stem cells improves aged oocyte quality and development potential by activating the ERK1/2 pathway Full Text
*The efficacy of platelet-rich plasma (PRP) alone or in combination with low intensity shock wave therapy (Li-SWT) in treating erectile dysfunction: a systematic review and meta-analysis of seven randomized controlled trials Full Text

Reviews
Design principles of gene circuits for longevity Full Text
The time is now: accounting for time-of-day effects to improve reproducibility and translation of metabolism research Full Text
Dietary Polyphenols as Geroprotective Compounds: From Blue Zones to Hallmarks of Ageing Full Text
Xenotopic synthetic biology: Prospective tools for delaying aging and age-related diseases Full Text

Senolytics/Senescent Cells
p53 enhances DNA repair and suppresses cytoplasmic chromatin fragments and inflammation in senescent cells Full Text
Cellular Senescence Is a Central Driver of Cognitive Disparities in Aging Full Text

Skin & Beauty
Young fibroblast-derived migrasomes alleviate keratinocyte senescence and enhance wound healing in aged skin Full Text
*A Pilot Randomized Controlled Trial (RCT) Evaluating the Efficacy of an Exosome-Containing Plant Extract Formulation for Treating Male Alopecia Full Text
*A Single-center, Double-blinded, Randomized, Placebo-controlled Trial Evaluating the Safety and Efficacy of a Dietary Supplement Containing Rosemary Extract on Visible Facial Skin Quality Full Text
Targeting IGF1-Induced Cellular Senescence to Rejuvenate Hair Follicle Aging Full Text
Youthful Brain-Derived Extracellular Vesicle-Loaded GelMA Hydrogel Promotes Scarless Wound Healing in Aged Skin by Modulating Senescence and Mitochondrial Function Full Text

Stem Cells
Human umbilical cord-derived mesenchymal stem cells improve thymus and spleen functions in d-galactose-induced aged mice Full Text
Amniotic fluid-derived mesenchymal stem cells as a therapeutic tool against cytokine storm: a comparison with umbilical cord counterparts Full Text

Telomeres
The relationship between telomere length and aging-related diseases Full Text

Odds & Sods
*Home-based heat therapy lowers blood pressure and improves endothelial function in older adults Full Text
*Photobiomodulation improves functional recovery after mild traumatic brain injury Full Text
*Practice makes perfect, but to what end? Computerised brain training has limited cognitive benefits in healthy ageing 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 we emerge from the depth of winter, this month we will take a look at how the combination of Omega 3, Vitamin D and resistance exercise can slow down the aging process; how young blood plasma can help with surgical outcomes in a human trial; how Klotho gene therapy can increase the lifespan of mice; and in the Canadian content study, how cellular reprogramming can protect retinal neurons and maintain vision in a mouse model of multiple sclerosis.

In the Supplemental Section, you’ll find in Lifestyle, the optimum combination of sleep, exercise and nutrition to reduce mortality; in Melatonin, how it can improve DNA damage repair; in Other Supplements, how we might need to increase our vitamin B12 intake; in Blood Factors, how young bone marrow transplantation delays bone aging; in Lifespan, how Glibenclamide increases mouse longevity; in Microbiome, how microbiota protect against frailty; and, in Senolytics, a pilot study of Dasatinib & Quercetin for Alzheimer’s.
(To make these suggestions easier to find, I’ve marked them with ***)

Canadian Longevity Association News

In February I got into the swing of producing weekly videos with four Longevity Snapshots being released. It’s already made a big difference to my stress levels, not having to record four or five videos in succession, and is enabling me to get stuck into other projects, which I will reveal at a later date.

We also onboarded a new volunteer this month, who is already playing an active role for us, so a warm welcome to Faye!

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.

February 2025 Highlights:

In this subanalysis of the DO-Health trail where older adults were treated with either individual or combinations of 1000 IU Vitamin D, 1g Omega 3 and 3/week resistance exercise over three years, found that Omega 3 supplementation and even more so the combination of all three treatments, slowed down biological aging according to four epigenetic age clocks. The effects were relatively modest, ranging from 2.9 to 3.8 months, but when extrapolated over a longer period of time, could make a substantial difference.
*Individual and additive effects of vitamin D, omega-3 and exercise on DNA methylation clocks of biological aging in older adults from the DO-HEALTH trial Full Text

It has been known for some time in old mice that giving them blood plasma from young mice can cause a fair amount of rejuvenation, however data from humans has been sorely lacking. In this innovative trial, researchers took advantage of the opportunity presented by older adults undergoing joint replacement surgery to see what would happen to their recovery if they gave them four transfusions of blood plasma taken from 35 year olds. This was a small study, but the results were encouraging, with the treated group recovering four days faster from fatigue and impairment of daily functioning, and six days faster from pain.
*Young Plasma Decreases Inflammation After Surgery in Trial Full Text

Klotho was one of the first longevity genes discovered in mice in the 1990’s and there has been considerable interest in bringing the benefits to humans. Unfortunately, the molecule is too big to cross the blood brain barrier and it would also be broken up by the digestive system, therefore gene therapy is a potential solution. Although there have been previous attempts at genetic manipulation, this is the first study to use a single dose in naturally aging normal mice. This led to a 20% increase in lifespan as well as improving physical fitness, muscular regenerative capacity and bone microstructure. An unrelated company is hoping to move Klotho gene therapy into human trials later this year.
A Klotho Gene Therapy Extends Life in Male Mice Full Text

Canadian Content Study

I was excited to see this study out of the lab of Alyson Fournier of McGill University, which is the first Canadian study that I have seen using cellular reprogramming for rejuvenation in multiple sclerosis. Using a mouse model, they successfully reduced the death of retinal ganglion cells (neurons in the eyes which transmit signals to the brain) and preserved the vision of the mice. As for next steps, I received correspondence from Alyson, who stated that they “are planning a study to do a pan-neuronal rescue with the OSK construct and to test if the intervention works if the mice are transduced following symptom onset.” It is great to see such research coming out of Canada and hope to see more of it!
Cellular rejuvenation protects neurons from inflammation-mediated cell death Full Text CAN

Further Canadian content is indicated by CAN

Supplemental Section

Lifestyle
*Minimum and optimal combined variations in sleep, physical activity, and nutrition in relation to all-cause mortality risk Full Text***

Fasting/Dietary Restriction
The Influence of Physical Exercise, Ketogenic Diet, and Time-Restricted Eating on De Novo Lipogenesis: A Narrative Review Full Text

Diet
*Multi-dimensional evidence from the UK Biobank shows the impact of diet and macronutrient intake on aging Full Text
*Alignment of menu items offered in Canadian long-term care homes with Canada’s food guide and the Diabetes Canada Clinical Practice Guidelines Full Text CAN
*Effectiveness of Protein-enriched oral nutritional supplements on muscle function in middle-aged and elderly women: A randomized controlled trial Full Text
*Mediterranean Diet and Quality of Life in Adults: A Systematic Review Full Text

Exercise
*Optimal dose and pattern of physical activity to prevent diagnosed depression: prospective cohort study Full Text
*The effect of an exercise- and passive-induced heat stress on autophagy in young and older males Full Text CAN
*Associations between the timing of 24 h physical activity and diabetes mellitus: results from a nationally representative sample of the US population Full Text

Non-prescription Supplements (in alphabetical order)

Curcumin
*Curcumin plus piperine improve body composition in patients with inflammatory bowel disease: a randomized, double-blind, placebo-controlled clinical trial

Melatonin
*Melatonin supplementation and oxidative DNA damage repair capacity among night shift workers: a randomised placebo-controlled trial Full Text CAN ***
*Evaluation of melatonin gel as local drug delivery system for the treatment of periodontitis: a split-mouth randomized controlled trial Full Text

Resveratrol
*Effects of resveratrol supplementation on serum concentrations of plasminogen activator inhibitor-1, fibroblast growth factor 21, and adiponectin in patients with nonalcoholic fatty liver disease Full Text
Resveratrol does not mimic the positive effects of calorie restriction on lifespan in Microcebus murinus Full Text

Spermidine
Effect of spermidine intake on overload-induced skeletal muscle hypertrophy in male mice Full Text
Natural Polyamine Spermidine Inhibits the In Vitro Oxidation of LDL Full Text

Other available supplements or natural substances (in alphabetical order)
*Withania somnifera (Ashwagandha) supplementation: a review of its mechanisms, health benefits, and role in sports performance Full Text
*'Healthy' vitamin B12 levels not enough to ward off neuro decline Full Text***
*Krill oil for knee osteoarthritis: A meta-analysis of randomized controlled trials Full Text
*Impact of Pomegranate Extract Supplementation on Physical and Cognitive Function in Community-Dwelling Older Adults Aged 55–70 Years: A Randomised Double-Blind Clinical Trial Full Text
*Urolithin A provides cardioprotection and mitochondrial quality enhancement preclinically and improves human cardiovascular health biomarkers Full Text
The polyphenol metabolite urolithin A suppresses myostatin expression and augments glucose uptake in human skeletal muscle cells Full Text

Combinations
*Effects of Accentuated Eccentric and Maximal Strength High-Resistance Training Programs with or Without a Curcumin-Based Formulation Supplement on Body Composition, Blood Pressure, and Metabolic Parameters in Older Adults Full Text
Synergistic effects of memantine and alpha7 nicotinic acetylcholine receptor agonist PHA-543613 to improve memory of aged rats Full Text
*The effects of lutein/ zeaxanthin (Lute-gen®) on eye health, eye strain, sleep quality, and attention in high electronic screen users: a randomized, double-blind, placebo-controlled study Full Text

Prescription Supplements

Metformin
*Impact of Prior Metformin Use on Stroke Outcomes: A Systematic Review and Updated Meta-Analysis Full Text
The Anti-Aging Mechanism of Metformin: From Molecular Insights to Clinical Applications Full Text

Rapamycin (sirolimus)
*Effectiveness and safety of liposomal rapamycin for the treatment of facial angiofibromas in tuberous sclerosis Full Text

Miscellaneous Molecules & Prescription Drugs
*Age and Sex Differences in Efficacy of Treatments for Type 2 Diabetes
A Network Meta-Analysis Full Text
Partial microglial depletion through inhibition of colony-stimulating factor 1 receptor improves synaptic plasticity and cognitive performance in aged mice Full Text

Novel Molecules
GDF15 Neutralization Ameliorates Muscle Atrophy and Exercise Intolerance in a Mouse Model of Mitochondrial Myopathy Full Text
*A Randomized Open-Label, Observational Study of the Novel Ketone Ester, Bis Octanoyl ®-1,3-Butanediol, and Its Acute Effect on ß-Hydroxybutyrate and Glucose Concentrations in Healthy Older Adults Full Text

Other Areas of Interest (in alphabetical order)

Blood Factors or other Heterochronic Transplantation
Young bone marrow transplantation delays bone aging in old mice Full Text CAN ***
Plasma therapy: a novel intervention to improve age-induced decline in deudenal cell proliferation in female rat model Full Text
Rejuvenating the gut: young plasma therapy improves cell proliferation, IGF-I and IGF-IR expression, and immune defense in aged male rats jejunum Full Text

Epigenetics & Cellular Reprogramming
Partial reprogramming by cyclical overexpression of Yamanaka factors improves pathological phenotypes of tauopathy mouse model of human Alzheimer's disease

Exosomes (small packets of information released by cells)
Golgi-restored vesicular replenishment retards bone aging and empowers aging bone regeneration Full Text
Mesenchymal stem cell exosome therapy: current research status in the treatment of neurodegenerative diseases and the possibility of reversing normal brain aging Full Text
Mesenchymal stem cell-derived extracellular vesicles attenuate ferroptosis in aged hepatic ischemia/reperfusion injury by transferring miR-1275 Full Text

Genetics including CRISPR
Restoring neuropetide Y levels in the hypothalamus ameliorates premature aging phenotype in mice Full Text
CRISPR/Cas9-Targeted Myostatin Deletion Improves the Myogenic Differentiation Parameters for Muscle-Derived Stem Cells in Mice Full Text
A Potential New Target for Normal Brain Aging Full Text

Lifespan Lengthening Interventions
Reduction of DNA Topoisomerase Top2 Reprograms the Epigenetic Landscape and Extends Health and Life Span Across Species Full Text
Glibenclamide targets MDH2 to relieve aging phenotypes through metabolism-regulated epigenetic modification Full Text***
HypoxyStat, a small-molecule form of hypoxia therapy that increases oxygen-hemoglobin affinity Full Text

Microbiome
*Dietary intake of live microbes and its association with frailty in older adults: a NHANES analysis (1999–2018) Full Text
Microbiota protect against frailty, loss of skeletal muscle, and maintain inflammatory tone during aging in mice Full Text CAN ***
*Augmenting Cognitive Function in the Elderly with Mild Cognitive Impairment Using Probiotic Lacticaseibacillus rhamnosus CBT-LR5: A 12-Week Randomized, Double-Blind, Parallel-Group Non-Comparative Study Full Text
*Aging Is Associated With Decreased Lactobacillus and Increased Cervicovaginal Inflammation in Canadian Women Full Text CAN

Observational Studies
*Receiving Care in Your Language Linked to Lower Health Risks Full Text CAN
*We are no longer living longer: Study across Europe Full Text
*Situations of Vulnerability, Life Satisfaction, and Social Support of Older Women and Men: Results From the Canadian Longitudinal Study on Aging (CLSA) CAN

Opinion/Editorials/Theory/Policy
A field guide to aging Full Text CAN
Playful brains: a possible neurobiological pathway to cognitive health in aging Full Text

Other Ageing Biology
Enhanced paracrine action of FGF21 in stromal cells delays thymic aging Full Text
Klotho protects INS-1 pancreatic β-cells from senescence and enhances mitochondrial function Full Text

Regenerative Medicine
Creating a Functional Pancreas From Human Cells Full Text

Reproductive Health
*Timing of menarche and menopause and epigenetic aging among U.S. adults: results from the National Health and Nutrition Examination Survey 1999–2002 Full Text
Nicotinamide Riboside Supplementation Alleviates Testicular Aging Induced by Disruption of Qprt-Dependent NAD+ De Novo Synthesis in Mice Full Text
Nicotinamide mononucleotide supplementation improves oocyte developmental
competence in different ovarian damage conditions Full Text

Reviews
Newer Therapeutic Approaches in Treating Alzheimer’s Disease: A Comprehensive Review Full Text
Non-pharmacological treatment of Alzheimer’s disease: an update Full Text
Recent advances in immunotherapy targeting CETP proteins for atherosclerosis prevention Full Text

Senolytics/Senescent Cells
Senolytic compounds reduce epigenetic age of blood samples in vitro Full Text
Study Shows Anti-Aging Potential for Insilico’s IPF Candidate Full Text
*A pilot study of senolytics to improve cognition and mobility in older adults at risk for Alzheimer’s disease Full Text***
*Preliminary Data on the Senolytic Effects of Agrimonia pilosa Ledeb. Extract Containing Agrimols for Immunosenescence in Middle-Aged Humans: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Comparison Study Full Text

Skin & Beauty
Synergistic Anti-Aging Effects of Adipose-Derived Stem Cell Extracellular Vesicles Loaded With Natural Compounds Full Text
Functional regeneration strategies of hair follicles: advances and challenges Full Text
Umbilical Cord Mesenchymal Stromal Cell-Derived Small Extracellular Vesicles Modulate Skin Matrix Synthesis and Pigmentation Full Text

Stem Cells
Sustaining Brain Youth by Neural Stem Cells: Physiological and Therapeutic Perspectives Full Text

Telomeres
Circular RNA Telomerase Reverses Endothelial Senescence in Progeria Full Text
37 kDa LRP::FLAG enhances telomerase activity and reduces ageing markers in vivo Full Text
Modification of the telomerase gene with human regulatory sequences resets mouse telomeres to human length Full Text

Odds & Sods
Effects of cannabis smoke and oral Δ9THC on cognition in young adult and aged rats
*Impact of deep brain stimulation on cognitive impairment in Parkinson’s disease: A retrospective longitudinal study 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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Kicking off the new year with a lifespan special, we will take a look at reversing the senescence of senescent cells to increase mouse lifespan; the discovery and beneficial effects of a subset of youthful stem cells which can also increase mouse longevity; the most comprehensive study of life-extending molecules in the roundworm c.elegans; and in the Canadian Content study, how disrupting the antioxidant defences in a specific organ in c.elegans can increase its lifespan.

In the Supplemental Section, you’ll find in Fasting, how 14 hrs fasting can improve cognition & sleep in older adults; in Diet, how carotenoid intake slows biological aging; in Exercise, how it can impact cancer; in Other Supplements, the benefits of ergothioneine found in mushrooms; in Combinations, how a four supplement combo shows benefits in Parkinson’s; in Reproductive Health, how OSKM gene therapy prolongs fertility; in Stem Cells, how they can reverse hearing loss; and in Odds & Sods, the life expectancy of cats in the UK. And of course much more!
(To make these suggestions easier to find, I’ve marked them with ***)

Canadian Longevity Association News

As you may have noticed, we’ve switched over to using Substack for these monthly reviews instead of Mailchimp, while still continuing to also use Patreon. Hopefully using Substack will expose us to a greater audience - it has already resulted in our first paid Substack subscription - thank you Cory!

The big news from January is that the CLA launched a new weekly video series, the first four episodes of which can be found here, or under the four highlighted studies below. Truth be told, we’re just dividing up the monthly video into weekly chunks to make the production less stressful, and to hopefully increase viewership by having shorter and more up to date videos. The weekly videos will still be compiled into a monthly roundup as you can see in the link above. With these new weekly videos, we finally took the plunge and started to post on TikTok as well.

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 TikTok

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.

January 2025 Highlights:

Senescent cells cause all kinds of dysfunction, and up until now, dealing with that dysfunction has involved either trying to remove those cells via senolytics, or stopping their release of inflammatory molecules via senomorphics. In this study, researchers have found a third method, which involves returning senescent cells to their original state, making them fully functional again. Exosomes were used to deliver a certain micro RNA which enabled the SCs to grow and divide again. The normal mice used in this study saw their appearance, physical performance and cognitive function improve. They also lived longer, with their average and maximum lifespans increasing by 15% and 12% respectively.
Exosomal miR-302b rejuvenates aging mice by reversing the proliferative arrest of senescent cells Full Text CLA Video Review

The aging of our stem cells is one of the primary drivers of our overall aging, however not all stem cells age at the same rate. In this study, researchers discovered that there is a small subset of our blood stem cells expressing low levels of the surface marker CD150 which exhibit a more youthful profile. When these stem cells were taken from old mice and given to other old mice, they rejuvenated the blood composition of the mice as well as improving their functional performance and lengthening their lives. Removing cells which produce high levels of CD150 could be a way to provide similar benefits to us.
Reducing functionally defective old HSCs alleviates aging-related phenotypes in old recipient mice Full Text Some Stem Cells Remain Youthful With Age - Lifespan.io Review
CLA Video Review

This is probably the most comprehensive study on lifespan extending molecules in the small roundworm c.elegans. The researchers tested 16 molecules which had previously been documented to increase c.elegans lifespan under a variety of conditions, finding out that those conditions played a pivotal role in whether or not the molecule successfully extended lifespan. They also tested combinations of the most successful molecules, finding out that most combinations did not produce an additive effect. In addition, they did a screen of other potential molecules, discovering five more that could extend c.elegans’ lifespan. This paper provided a cautionary note about trusting single molecule studies and the potential pitfalls of combining substances, especially as many longevity enthusiasts combine multiple supplements.
Comprehensive evaluation of lifespan-extending molecules in C. elegans Full Text
CLA Video Review

Canadian Content Study

Another c.elegans lifespan study coming from the lab of Jeremy Van Raamsdonk out of McGill, this time looking at how disrupting antioxidant defences in various tissues impacts lifespan. Building on their previous work they found that disrupting the production of superoxide dismutase (SOD) , one of our main antioxidants, only in the intestines could have the same life-extending effect as disrupting it throughout the worm's body. This is very basic research, and it will be a while before we know where this leads, but great that research like this is being done in Canada.
Intestine-specific disruption of mitochondrial superoxide dismutase extends longevity Full Text
CLA Video Review
Further Canadian content is indicated by CAN

Supplemental Section

Lifestyle
*Cognitive function differs across healthy lifestyle behavior profiles: a 10-year population-based prospective cohort study Full Text
*Effects of multidomain lifestyle intervention on frailty among older men and women – a secondary analysis of a randomized clinical trial Full Text

Fasting/Dietary Restriction – certainly the cheapest & also one of the most effective anti-ageing interventions currently available. It comes in many flavours, but I fast for at least 12 hours every day.
*Prolonged nightly fasting in older adults with memory decline: A single-group pilot study exploring changes in cognitive function and cardiometabolic risk factors Full Text***
Intermittent Fasting Enhances Motor Coordination Through Myelin Preservation in Aged Mice Full Text
*The Effects of Time-Restricted Eating on Inflammation and Oxidative Stress in Overweight Older Adults: A Pilot Study Full Text

Diet – let food be thy medicine…
*Dietary carotenoid intakes and biological aging among US adults, NHANES 1999–2018 Full Text***
*The role of the Mediterranean diet in reducing the risk of cognitive impairement, dementia, and Alzheimer’s disease: a meta-analysis Full Text
*Long-Term Intake of Red Meat in Relation to Dementia Risk and Cognitive Function in US Adults
*Coffee drinking timing and mortality in US adults Full Text
*Dietary carbohydrate quality is associated with epigenetic age acceleration: a cross-sectional study of the CARDIA cohort Full Text

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*Global consensus on optimal exercise recommendations for enhancing healthy longevity in older adults (ICFSR) Full Text Full Text *Commentary
*Muscle Strength, Fitness Linked to Lower Mortality Risk in Patients With Cancer Abstract***
*Physical Activity and Life Expectancy Free of Cancer: Prospective Evidence From the UK Biobank Study Full Text***

Non-prescription Supplements (in alphabetical order)

Astaxanthin
Astaxanthin-loaded polylactic acid-glycolic acid nanoparticles alleviates atherosclerosis by suppressing macrophage ferroptosis via the NRF2/SLC7A11/GPX4 pathway Full Text
Astaxanthin Alleviates Lung Injury by Regulating Oxidative Stress, Inflammatory Response, P2X7 Receptor, NF-κB, Bcl-2, and Caspase-3 in LPS-Induced Endotoxemia Full Text

Curcumin
*Does curcumin supplementation affect inflammation, blood count and serum brain-derived neurotropic factor concentration in amateur long-distance runners? Full Text
*Immunomodulatory effects of novel nano micelle based curcumin in rheumatoid arthritis patients: A double blind randomized clinical trial Full Text
Combined effect of exercise and curcumin on inflammation-associated microRNAs and cytokines in old male rats: A promising approach against inflammaging Full Text

Fisetin
Exploring the Molecular Mechanisms of Fisetin in Treating Periodontitis Through Multiomics and Network Pharmacology Full Text

Melatonin
*Effects of Melatonin Supplementation on Muscle Strength, Manual Dexterity, and Postural Balance in Patients Living with Multiple sclerosis - A Randomized Controlled Trial

Nicotinamide MonoNucleotide (NMN)
Administration of nicotinamide mononucleotide suppresses the progression of age-related hearing loss in mice
Nicotinamide mononucleotide restores impaired metabolism, endothelial cell proliferation and angiogenesis in old sedentary male mice Full Text

Nicotinamide Riboside (NR)
*Cognitive and Alzheimer's disease biomarker effects of oral nicotinamide riboside (NR) supplementation in older adults with subjective cognitive decline and mild cognitive impairment Full Text
*A Pilot Trial of Nicotinamide Riboside and Coenzyme Q10 on Inflammation and Oxidative Stress in Chronic Kidney Disease
Nicotinamide riboside supplementation ameliorates ovarian dysfunction in a PCOS mouse model Full Text

Resveratrol
*The efficacy of resveratrol supplementation on inflammation and oxidative stress in type-2 diabetes mellitus patients: randomized double-blind placebo meta-analysis Full Text
The Antiaging and Antioxidative Effects of a Combination of Resveratrol and High-Intensity Interval Training on the Frontal Lobe in Aged Rats: The Role of SIRTS 4, SIRTS 5, SOD1, and SOD2 Full Text
Resveratrol enhances post-injury muscle regeneration by regulating antioxidant and mitochondrial biogenesis Full Text

Spermidine
*The Associations of Dietary Polyamines with Incident Type 2 Diabetes Mellitus: A Large Prospective Cohort Study Full Text
*Spermidine Recovers the Autophagy Defects Underlying the Pathophysiology of Cell Trafficking Disorders Full Text

Other available supplements or natural substances (in alphabetical order)
Long-Term Creatine Supplementation Improves Cognitive and Hippocampal Structural Plasticity Impairments in a D-Gal-Induced Aging Model via Increasing CK-BB Activity in the Brain Full Text
*Dietary vitamin D intake and changes in body composition over three years in older adults with metabolic syndrome Full Text
Long-term intake of Tamogi-take mushroom (Pleurotus cornucopiae) mitigates age-related cardiovascular dysfunction and extends healthy life expectancy Full Text***
Ergothioneine improves healthspan of aged animals by enhancing cGPDH activity through CSE-dependent persulfidation Full Text***
The role of vitamin K2 in cognitive impairment: linking vascular health to brain health Full Text
Effects of Korean red ginseng on auditory, cognitive, and liver functions in a naturally aged mouse model Full Text

Combinations
Combination of rapamycin and adipose-derived mesenchymal stromal cells enhances therapeutic potential for osteoarthritis Full Text
*Multi-omics characterization of improved cognitive functions in Parkinson’s disease patients after the combined metabolic activator treatment: a randomized, double-blinded, placebo-controlled phase II trial Full Text***
*Dapagliflozin combined with metformin improves blood glucose, bone metabolism and bone mineral density in elderly patients with type 2 diabetes mellitus complicated with osteoporosis Full Text

Prescription Supplements

Rapamycin (sirolimus)
*The bioavailability and blood levels of low-dose rapamycin for longevity in real-world cohorts of normative aging individuals Full Text

Miscellaneous Molecules & Prescription Drugs
*Use of SGLT2 Inhibitors in Frail Older Adults is Associated with Increased Survival: A Retrospective Study

Other Areas of Interest (in alphabetical order)

Ageing Clocks & other biomarkers of ageing
Why our biological clock ticks: Research reconciles major theories of aging Abstract
estiMAge: development of a DNA methylation clock to estimate the methylation age of single cells Full Text
*Cross-tissue comparison of epigenetic aging clocks in humans Full Text

Biomarkers
*Longitudinal serum proteome mapping reveals biomarkers for healthy ageing and related cardiometabolic diseases Full Text
*Mid-life anti-inflammatory metabolites are inversely associated with long-term cardiovascular disease events Full Text

Epigenetics & Cellular Reprogramming
*Methylome analysis in long-lived men deciphers DNA methylation modifications associated with male longevity in humans Full Text

Exosomes (small packets of information released by cells)
Exosome-based targeted delivery of NF-κB ameliorates age-related neuroinflammation in the aged mouse brain Full Text
Mesenchymal stem cells derived exosomes: a new era in cardiac regeneration Full Text

Genetics including CRISPR
*SNP rs6543176 is associated with extreme human longevity but increased risk for cancer
Age-invariant genes: multi-tissue identification and characterization of murine reference genes Full Text

Lifespan Lengthening Interventions
Ginkgolide B increases healthspan and lifespan of female mice
Dietary cinnamon promotes longevity and extends healthspan via mTORC1 and autophagy signaling Full Text
Activation of Nuclear Receptor CAR: A Pathway to Delay Aging through Enhanced Capacity for Xenobiotic Resistance Full Text
L-Theanine Extends the Lifespan of Caenorhabditis elegans by Reducing the End Products of Advanced Glycosylation Full Text

Microbiome
*New study reveals how a 'non-industrialized' style diet can reduce risk of chronic disease Full Text CAN
Maintaining Muscle by Restoring Gut Bacteria Full Text
Probiotics Slow Down Alzheimer’s Disease in Mice Full Text
Fecal Microbiota Transplantation from Young-Trained Donors Improves Cognitive Function in Old Mice Through Modulation of the Gut-Brain Axis Full Text

Observational Studies
*Antibiotics, vaccinations and anti-inflammatory medication linked to reduced risk of dementia Full Text
*Peaceful dying among Canada’s elderly: An analysis of the Canadian Longitudinal Study on Aging Full Text CAN
*Evaluating vitamin C-related gene-environment and metabolite-environment interaction effects on intraocular pressure in the Canadian Longitudinal Study on Aging Full Text CAN
*Marital and living status and biological ageing trajectories: a longitudinal cohort study with a 20-year follow-up Full Text

Opinion/Editorials/Theory/Policy
Estimating the Effect of Adhering to the Recommendations of the 2019 Canada’s Food Guide on Health Outcomes in Older Adults: Protocol for a Target Trial Emulation Full Text CAN
Use of lecanemab and donanemab in the Canadian healthcare system: Evidence, challenges, and areas for future research Full Text CAN
Mikhail ‘Misha’ Blagosklonny’s enduring legacy in geroscience: the hyperfunction theory and the therapeutic potential of rapamycin Full Text
Aging and Cancer—Inextricably Linked Across the Lifespan Full Text
The Genetic and Epigenetic Arms of Human Ageing and Longevity Full Text

Other Ageing Biology
Delivery of FGF18 using mRNA-LNP protects the cartilage against degeneration via alleviating chondrocyte senescence Full Text
NAD World 3.0: the importance of the NMN transporter and eNAMPT in mammalian aging and longevity control Full Text

Regenerative Medicine
Tenascin-C promotes bone regeneration via inflammatory macrophages Full Text

Reproductive Health
How the Yamanaka Factors Affect Female Reproduction in Rats
Oct4, Sox2, Klf4, c-My (OSKM) gene therapy in the hypothalamus prolongs fertility and ovulation in female rats Full Text***
*Hormone replacement therapy, menopausal age and lifestyle variables are associated with better cognitive performance at follow-up but not cognition over time in older-adult women irrespective of APOE4 carrier status and co-morbidities Full Text

Reviews
From molecular to physical function: The aging trajectory Full Text CAN
High-Intensity and/or High-Volume Exercise Training: Double-Edged Sword Effects of Vigorous Physical Activity in Elderly People and/or in Middle-Age Cancer-Therapy-Treated Patients Full Text CAN
Deep learning and generative artificial intelligence in aging research and healthy longevity medicine Full Text

Senolytics/Senescent Cells
Dasatinib and Quercetin Limit Gingival Senescence, Inflammation, and Bone Loss Full Text
The senolytic cocktail, dasatinib and quercetin, impacts the chromatin structure of both young and senescent vascular smooth muscle cells Full Text
Transcriptomic signatures and network-based methods uncover new senescent cell anti-apoptotic pathways and senolytics Full Text
AP2A1 modulates cell states between senescence and rejuvenation Full Text

Skin & Beauty
*Exosomes for Aesthetic Dermatology: A Comprehensive Literature Review and Update Full Text
*Biotechnological Phytocomplex of Zanthoxylum piperitum (L.) DC. Enhances Collagen Biosynthesis In Vitro and Improves Skin Elasticity In Vivo Full Text
Protective Effect of Conditioned Medium of Immortalized Human Stem Cells from Exfoliated Deciduous Teeth Against Hair Graying Caused by X-Ray Irradiation via Its Antioxidative Activity Full Text
The Effect of Local Hyaluronic Acid Injection on Skin Aging: A Systematic Review and Meta-Analysis Full Text

Stem Cells
Innovative treatment of age-related hearing loss using MSCs and EVs with Apelin Full Text***

Telomeres
*Effect of Physical Exercise on Telomere Length: Umbrella Review and Meta-Analysis Full Text
*Diet, lifestyle and telomere length: using Copula Graphical Models on NHANES data Full Text

Odds & Sods
Life expectancy of cats in Britain: moggies and mollies live longer Full Text***
Tree shrew as a new animal model for musculoskeletal disorders and aging 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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Hello and welcome to the final longevity review of 2024. This month we will take a look at gene therapy to increase telomere length; freeing the immune system to remove senescent cells; using probiotics to help with sarcopenia; and, in the Canadian content study, employing extracellular vesicles to deliver drugs to the brain to combat neuroinflammation.

In the Supplemental Section, you’ll find in Lifestyle how exercise and sleep improve memory the next day; in Diet, how moderate wine consumption can lower CVD risk, and how a well-balanced vegan diet can stimulate protein production as much as an omnivorous diet; in Exercise, a systematic review on HIIT and cognition; in Curcumin, a systematic review of its effects on exercise; in Miscellaneous Molecules, a systematic review of anti-diabetic medication’s anti-dementia benefits; in Novel Molecules, another AI generated drug; in Blood Factors, umbilical cord blood infusions helped with AML; in Exosomes, a review of their application in aging related diseases; in Genetics, gene therapy for hearing loss; in Observational, how intrinsic capacity in old age is greater in later born birth cohorts; in Other, RANKL treatment can restore the thymus; in Reproduction, berberine promotes aged fertility; in Senolytics, ABT-263 for aged skiing and wound healing; and, in Stem Cells, a review of their effectiveness for osteoarthritis.
(To make these suggestions easier to find, I’ve marked them with ***)

Canadian Longevity Association News

If you haven’t heard already, the CLA has opened up its own online store where you can buy CLA branded merchandise - all proceeds of course going to the CLA to further our activities.

We also have big plans for 2025, which will be revealed in due course - so watch this space!

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.

December 2024 Highlights:

In this study, the potential of using gene therapy to extend telomere length was examined. Telomeres shorten with age and previous studies have shown that lengthening them can improve lifespan and other health benefits. Although the type of gene therapy used couldn’t be used in humans, the results nonetheless impressive, with one group of mice having an almost 50% increase in lifespan, which is the largest increase in mouse lifespan that I have seen. In addition, they showed great regenerative potential with improved skin wound healing and recovery from induced colitis.
Telomerase reverse transcriptase gene knock-in unleashes enhanced longevity and accelerated damage repair in mice Full Text

Senolytics (the removal of senescent, or zombie cells) have been in development for some time and have mainly focused on killing the cells directly by using molecules to have them commit suicide or engineering CAR-T cells to remove them. However, the immune system should be clearing senescent cells on its own, and that is what the researchers here have developed, by targeting a molecule (ganglioside GD3) on the surface of senescent cells which was hiding them from the immune system. Once removed, natural killer cells homed in on them and removed them. This could be a more selective and natural way of removing senescent cells.
A ganglioside-based immune checkpoint enables senescent cells to evade immunosurveillance during aging Full Text

In this study in both mice and sarcopenic humans (sarcopenia is the debilitating loss of muscle function with age), a probiotic containing a strain of Bifidobacterium animalis was able to improve muscle function and physical performance. It also changed the gut microbiota and their metabolites in a beneficial direction, and raised levels of creatine, which is important for muscles. It should be noted that there was no placebo control in the human study, but if larger placebo controlled studies are successfully carried out, then this could be an inexpensive way to alleviate sarcopenia.
*Bifidobacterium animalis Probio-M8 improves sarcopenia physical performance by mitigating creatine restrictions imposed by microbial metabolites Full Text

Canadian Content Study

I was pleasantly surprised to see this study, as it marks the first time that I have seen work coming from Canada on extracellular vesicles(EVs). The researchers, led by Charles Ramassamy and first author Rummenigge Oliveira Silva from the Armand-Frappier Santé Biotechnologie Research Centre, used EVs from human plasma and fat cells to cross the blood brain barrier to deliver donepezil, a drug used in Alzheimer’s which is also anti-inflammatory, to zebrafish larvae. This resulted in not only reduced inflammation but also increased movement when challenged with an inflammatory molecule. EVs show great potential for longevity, and I hope to see this work continued in Canada.
Exploring the potential of plasma and adipose mesenchymal stem cell-derived extracellular vesicles as novel platforms for neuroinflammation therapy Full Text CAN

Not a study, but a review of the accomplishments of the Canadian Consortium on Neurodegeneration in Aging (CCNA), which has been running since 2014 and involves teams across Canada co-ordinating together to tackle dementia. This has resulted in the creation of a national dementia program, CAN-THUMBS UP. “CCNA is evidence that an organized “centrally-organized” approach to dementia research can catalyze important progress nationally and yield significant and measurable results.”

We need to set up something similar devoted to longevity and aging in general - the CLA will make that happen!

Impact of a national dementia research consortium: The Canadian Consortium on Neurodegeneration in Aging (CCNA) Full Text CAN

Further Canadian content is indicated by CAN

Supplemental Section

Lifestyle
*Tissue-specific methylomic responses to a lifestyle intervention in older adults associate with metabolic and physiological health improvements Full Text
*Associations of accelerometer-measured physical activity, sedentary behaviour, and sleep with next-day cognitive performance in older adults: a micro-longitudinal study Full Text***
*Effectiveness and feasibility of a theory-informed intervention to improve Mediterranean diet adherence, physical activity and cognition in older adults at risk of dementia: the MedEx-UK randomised controlled trial Full Text

Fasting/Dietary Restriction
*Effect of Three Different Daily Protein Intakes in a Two-Meal Eating Pattern on Protein Turnover in Middle Age and Older Adults: A Randomized Controlled Trial
*Multi-omic analysis of biological aging biomarkers in long-term calorie restriction and endurance exercise practitioners: A cross-sectional study Full Text
*The effect of Ramadan intermittent fasting on anthropometric, hormonal, metabolic, inflammatory, and oxidative stress markers in pre-and post-menopausal women: a prospective cohort of Saudi women Full Text

Diet
*Cardiovascular Protection Tracks With Wine Intake, Now Provable With Urinary Marker Full Text***
*A well-balanced vegan diet does not compromise daily mixed muscle protein synthesis rates when compared to an omnivorous diet in active older adults: a randomized controlled cross-over trial Full Text***
*Slower Pace of Epigenetic Aging and Lower Inflammatory Indicators in Females Following a Nutrient-Dense, Plant-Rich Diet Than Those in Females Following the Standard American Diet Full Text

Exercise
*The effects of high-intensity interval training on cognitive performance: a systematic review and meta-analysis Full Text***
*Exercise training alters resting brain-derived neurotrophic factor concentration in older adults: A systematic review with meta-analysis of randomized-controlled trials Full Text
*Long-term impact of adherence to muscle-strengthening guidelines on inflammation markers: a 17-year follow-up study with obesity parameters as mediators Full Text

Non-prescription Supplements (in alphabetical order)

Astaxanthin
Delivery systems for astaxanthin: A review on approaches for in situ dosage in the treatment of inflammation associated diseases Full Text
Biological activities of astaxanthin in the treatment of neurodegenerative diseases
Oral administration of astaxanthin mitigates chronological skin aging in mice

Curcumin
*Evaluation of curcumin intake in reducing exercise-induced muscle damage in athletes: a systematic review Full Text***
Efficacy and mechanisms of curcumin in the treatment of osteoarthritis: A scoping review Full Text
The Dynamic Role of Curcumin in Mitigating Human Illnesses: Recent Advances in Therapeutic Applications Full Text

Fisetin
Fisetin as a Blueprint for Senotherapeutic Agents — Elucidating Geroprotective and Senolytic Properties with Molecular Modeling Full Text

Melatonin
*12-week melatonin intake attenuates cardiac autonomic dysfunction and oxidative stress in multiple sclerosis patients: a randomized controlled trial
The potential therapeutic role of melatonin in organ fibrosis: a comprehensive review Full Text
Protective Effects of Exogenous Melatonin Administration on White Fat Metabolism Disruption Induced by Aging and a High-Fat Diet in Mice Full Text

Nicotinamide MonoNucleotide (NMN)
Rejuvenating aged osteoprogenitors for bone repair Full Text

Resveratrol
Resveratrol alleviates heart failure by activating foxo3a to counteract oxidative stress and apoptosis Full Text
Resveratrol and Extra Virgin Olive Oil: Protective Agents Against Age-Related Disease Full Text

Spermidine
*The Association of Dietary Polyamines with Mortality and the Risk of Cardiovascular Disease: A Prospective Study in UK Biobank Full Text
Spermidine Enhances Mitochondrial Bioenergetics in Young and Aged Human-Induced Pluripotent Stem Cell-Derived Neurons Full Text
Spermidine alleviates thymopoiesis defects and aging of the peripheral T-cell population in mice after radiation exposure Full Text

Other available supplements or natural substances (in alphabetical order)
*Beta-Alanine for Improving Exercise Capacity, Muscle Strength, and Functional Performance of Older Adults: A Systematic Review
*The impact of creatine levels on musculoskeletal health in the elderly: a mendelian randomization analysis Full Text
*The power of creatine plus resistance training for healthy aging: enhancing physical vitality and cognitive function Full Text
*The Association Between Dietary Magnesium Intake and Frailty in Patients with Chronic Obstructive Pulmonary Disease: National Health and Nutrition Examination Survey Full Text
The Neuroprotective Effect of Rooibos Herbal Tea Against Alzheimer's Disease: A Review Full Text
*The effects of whey protein supplementation on indices of cardiometabolic health: A systematic review and meta-analysis of randomized controlled trials Full Text

Combinations
*Comparative Efficacy of Glucosamine-Based Combination Therapies in Alleviating Knee Osteoarthritis Pain: A Systematic Review and Network Meta-Analysis Full Text
Co-administration of coenzyme Q10 and curcumin mitigates cognitive deficits and exerts neuroprotective effects in aluminum chloride-induced Alzheimer's disease in aged mice Full Text

Prescription Supplements

Metformin
*Metformin Treatment With or Without Mediterranean Diet for the Prevention of Age-Related Diseases in People With Metabolic Syndrome: The MeMeMe Randomized Trial Full Text
A Systematic Review on Clinical Evidence for Topical Metformin: Old Medication With New Application Full Text
Metformin in Antiviral Therapy: Evidence and Perspectives Full Text

Rapamycin (sirolimus)
Rapamycin administration causes a decrease in muscle contractile function and systemic glucose intolerance concomitant with reduced skeletal muscle Rictor, the mTORC2 component, expression independent of energy intake in young rats Full Text

Miscellaneous Molecules & Prescription Drugs
*Anti-diabetic agents and the risks of dementia in patients with type 2 diabetes: a systematic review and network meta-analysis of observational studies and randomized controlled trials Full Text***
Losartan attenuates sex-dependent hypertension, neuroinflammation, and cognitive impairment in the aging male sprague–dawley rat Full Text
Spotlight on the Mechanism of Action of Semaglutide Full Text

Novel Molecules
Intestinal mucosal barrier repair and immune regulation with an AI-developed gut-restricted PHD inhibitor Full Text*** CAN
The metabolically resistant apelin-17 analog LIT01-196 reduces cardiac dysfunction and remodeling in heart failure after myocardial infarction Full Text
*Safety, Tolerability and Pharmacokinetic-Pharmacodynamic Relationship of NX210c Peptide in Healthy Elderly Volunteers: Randomized, Placebo-Controlled, Double-Blind, Multiple Ascending Dose Study Full Text

Other Areas of Interest (in alphabetical order)

Ageing Clocks & other biomarkers of ageing
*Metabolomic age (MileAge) predicts health and life span: A comparison of multiple machine learning algorithms Full Text
Critical review of aging clocks and factors that may influence the pace of aging Full Text
The Immunosenescence Clock: A New Method for Evaluating Biological Age and Predicting Mortality Risk Full Text

Biomarkers
An expert consensus statement on biomarkers of ageing for use in intervention studies Full Text
*Phenotypic upregulation of hexocylceramides and ether-linked phosphocholines as markers of human extreme longevity Full Text
*Biomarkers of cellular senescence and major health outcomes in older adults Full Text

Blood Factors or other Heterochronic Transplantation
The dominance of old blood, and age-related increase in protein production and noise Full Text
*A phase 2 pilot study of umbilical cord blood infusion as an adjuvant consolidation therapy in elderly patients with acute myeloid leukemia Full Text***

Exosomes (small packets of information released by cells)
*Plasma extracellular vesicles carry immune system-related peptides that predict human longevity Full Text
Comparative Analysis of the Therapeutic Potential of Extracellular Vesicles Secreted by Aged and Young Bone Marrow-Derived Mesenchymal Stem Cells in Osteoarthritis Pathogenesis Full Text
Mesenchymal Stem Cell-Derived Exosomes: A Promising Therapeutic Strategy for Age-Related Diseases Full Text***

Genetics including CRISPR
A Potential Gene Therapy for Hearing Loss Full Text***
Cardiac bridging integrator 1 gene therapy rescues chronic non-ischemic heart failure in minipigs Full Text
*Lack of association between common polymorphisms associated with successful aging and longevity in the population of Sardinian Blue Zone Full Text

Lifespan Lengthening Interventions
Lithocholic acid phenocopies anti-ageing effects of calorie restriction Full Text
Lifelong Glutathione Deficiency in Mice Increased Lifespan and Delayed Age-Related Motor Declines Full Text
Hesperetin Increases Lifespan and Antioxidant Ability Correlating with IIS, HSP, mtUPR, and JNK Pathways of Chronic Oxidative Stress in Caenorhabditis elegans Full Text

Microbiome
*Diet-gut microbiome interaction and its impact on host blood glucose homeostasis: a series of nutritional n-of-1 trials Full Text
*Impact of daily avocado consumption on gut microbiota in adults with abdominal obesity: an ancillary study of HAT, a randomized controlled trial Full Text
Gut microbiota metabolism of branched-chain amino acids and their metabolites can improve the physiological function of aging mice Full Text

Observational Studies
*Dementia Incidence in Quebec Over 20 Years Full Text CAN
*New Disability in a Cohort Study of Older Men—The Manitoba Follow-Up Study Full Text CAN
*Adverse changes in close social ties in aging women and men: A population-based longitudinal study of the CLSA (2011–2021) Full Text CAN
*Impact of Age on Rheumatic Immune-related Adverse Events: Experience from the Canadian Research Group of Rheumatology in Immuno-Oncology (CanRIO) CAN
*A standard procedure for constructing a multi-level social vulnerability index using CLSA and SOS data as working examples Full Text CAN
*Association of urban green and blue space with accelerated ageing: A cohort Study in the UK Biobank Full Text
*Cohort trends in intrinsic capacity in England and China Full Text

Opinion/Editorials/Theory/Policy
Canadian Clinical Guidelines on Social Isolation and Loneliness in Older Adults Full Text CAN
*Determinants of First Practice Location among Canadian Geriatric Medicine Trainees and Recent Graduates: Findings of a Cross-sectional Survey in 2023 Full Text CAN
Validation requirements for AI-based intervention-evaluation in aging and longevity research and practice Full Text
Disagreement on foundational principles of biological aging Full Text
On the causal connection in lifespan correlations and the possible existence of a ‘number of life’ at molecular level Full Text

Other Ageing Biology
Predicting the pro-longevity or anti-longevity effect of model organism genes with enhanced Gaussian noise augmentation-based contrastive learning on protein–protein interaction networks Full Text
Effects of Aging on Glucose and Lipid Metabolism in Mice Full Text
RANKL treatment restores thymic function and improves T cell–mediated immune responses in aged mice***

Reproductive Health
Berberine promotes primordial follicle activation and increases ovulated oocyte quantity in aged mice Full Text***
Dietary supplementation with lycopene improves semen quality and antioxidant status in breeder roosters Full Text
Canagliflozin treatment prevents follicular exhaustion and attenuates hallmarks of ovarian aging in genetically heterogenous mice

Reviews
Chaperone-mediated autophagy as a modulator of aging and longevity Full Text
Epigenetic modifications and emerging therapeutic targets in cardiovascular aging and diseases Full Text
Centenarians—the way to healthy vascular ageing and longevity: a review Full Text

Senolytics/Senescent Cells
Topical ABT-263 treatment reduces aged skin senescence and improves subsequent wound healing Full Text***
Precision Targeting of Senescent Cells Full Text
Senolysis by GLS1 Inhibition Ameliorates Kidney Aging by Inducing Excessive mPTP Opening through MFN1 Full Text
Generation of a selective senolytic platform using a micelle-encapsulated Sudan Black B conjugated analog Full Text

Skin & Beauty
*Efficacy and Safety of Topical Application of Plant-Based Products on Skin Aging in Healthy Individuals: A Systematic Review and Meta-Analysis of Randomized Controlled Trials Full Text
*Effects of Retinol, Natural Pea Peptide and Antioxidant Blend in a Topical Formulation: In Vitro and Clinical Evidence Full Text
*Phytoestrogens as Natural Anti-Aging Solutions for Enhanced Collagen Synthesis in Skin Full Text
*Silybum marianum Extract: A Highly Effective Natural Alternative to Retinoids to Prevent Skin Aging Without Side Effects Full Text

Stem Cells
*Safety and efficacy of autologous adipose-derived stem cells for knee osteoarthritis in the elderly population: A systematic review Full Text***
iPSC-derived mesenchymal stromal cells stimulate neovascularization less than their primary counterparts Full Text

Telomeres
Oral intake of degalactosylated whey protein increases peripheral blood telomere length in young and aged mice Full Text
*DNA methylation-based telomere length is more strongly associated with cardiovascular disease and long-term mortality than quantitative polymerase chain reaction-based telomere length: evidence from the NHANES 1999–2002 Full Text
The relationship between mitochondrial health, telomerase activity and longitudinal telomere attrition, considering the role of chronic stress Full Text

Odds & Sods
Hydra has mammal-like mutation rates facilitating fast adaptation despite its nonaging phenotype Full Text
Hallmarks of aging: A user’s guide for comparative biologists Full Text
Extreme longevity may be the rule not the exception in Balaenid whales 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 we get closer to the holiday season, this review returns to its monthly format after a brief foray into a bi-monthly issue. Now that I have caught up with these reviews, we will take a look at how 16:8 time restricted eating in healthy, normal weight individuals can still reduce weight and fat mass, as well as improve the immune system and make their gut microbiome younger; how ergothioneine could improve cognition in older individuals with mild cognitive impairment; and for the first time, two Canadian Content Studies, the first of which looks at how senolytics could help with multiple sclerosis, while the second investigates how pterostilbene targets the hallmarks of aging.

In the Supplemental Section, you’ll find in Diet, how the purple colour of fruits and vegetables reduces mortality; in Exercise, how a home exercise program can prevent falls; in Combinations, how resveratrol and vitamin C reduce oxidative stress in women; in Exosomes, how extracellular vesicles could combat Alzheimer’s and arthritis; in Reproductive Health, how stem cells extended the reproductive life of monkeys; and, in Stem Cells, how vision was restored through their use. And, of course, much more!

(To make these suggestions easier to find, I’ve marked them with ***)

Canadian Longevity Association News

If you missed last month’s news, we’ve opened up an online store where you’ll be able to buy CLA branded merchandise! All proceeds go directly to the CLA to help fund our activities to bring healthy longevity to all Canadians.

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.

November 2024 Highlights:

In this study of intermittent fasting, participants undertook a 16:8 Time Restricted Eating regimen over 30 days. Over that time, despite not reducing their caloric intake, the participants lost weight and fat mass, their senescent immune cells decreased, and their gut microbiome had a more youthful profile.
*Time-restricted eating reveals a “younger” immune system and reshapes the intestinal microbiome in humans Full Text

In this small year-long study in older adults with mild cognitive impairment, 25 mg of ergothioneine (the main active ingredient in mushrooms) three times a week, saw improvements in learning ability and memory, though other cognitive tests did not improve. A common marker for neurodegeneration and damage, neurofilament light chain (which is also elevated in traumatic brain injuries), remained stable while it increased substantially in the placebo group
*Investigating the efficacy of ergothioneine to delay cognitive decline in mild cognitively impaired subjects: A pilot study Full Text

Canadian Content Studies

I was delighted to find this study, as it is the first Canadian senolytic study that I am aware of. Researchers from McGill University looked at how a senolytic, Navitoclax, can impact a mouse model of multiple sclerosis. After first confirming that senescent microglia (a type of immune cell in the brain) play a role in disease progression, they then went about removing those cells. The results were that compared to the control, the treated mice had decreased disease severity, improved sight and neuronal survival, reduced demyelination and inflammation.
Senolytic treatment diminishes microglia and decreases severity of experimental autoimmune encephalomyelitis Full Text CAN

In this study, researchers from the University of British Columbia, looked at how pterostilbene (found in blueberries and closely related to resveratrol) targets the hallmarks of aging via the up and down regulation of related genes. Several hallmarks were positively affected, with decreases in inflammatory immune responses having the biggest number of changed genes. “Pterostilbene target genes are enriched with functions that are tightly connected to slowing down aging and potentially increasing lifespan.”
Pterostilbene Targets Hallmarks of Aging in the Gene Expression Landscape in Blood of Healthy Rats Full Text CAN

Further Canadian content is indicated by CAN

Supplemental Section

Lifestyle
*The effect of multidomain lifestyle intervention on health care service use and costs - secondary analyses from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER): a randomised controlled trial Full Text
*Lifestyle factors and incident multimorbidity related to chronic disease: a population-based 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.
Ramadan fasting model modulates biomarkers of longevity and metabolism in male obese and non-obese rats Full Text
Energy metabolism dysregulation, cerebrovascular aging, and time-restricted eating: Current evidence and proof-of-concept findings Full Text

Diet – let food be thy medicine…
*Association of dietary anthocyanidins intake with all-cause mortality and cardiovascular diseases mortality in USA adults: a prospective cohort study Full Text***
Impact of Coffee Intake on Human Aging: Epidemiology and Cellular Mechanisms Full Text
*Nut consumption and disability-free survival in community-dwelling older adults: a prospective cohort study Full Text

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*Acute exercise boosts NAD+ metabolism of human peripheral blood mononuclear cells Full Text
*High-intensity interval exercise is more efficient than medium intensity exercise at inducing neurogenesis Full Text
*Association of cognitive performance with overall, dosage, intensity, and domain physical activity in aging: NHANES 2011–2014 Full Text
*Effect of a home-based exercise program on subsequent falls among community-dwelling older adults with cognitive frailty: A sub-group analysis of a randomized controlled trial Full Text*** CAN

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.
*Impact of astaxanthin supplementation on markers of cardiometabolic health and tactical performance among firefighters Full Text
The effect of long term astaxanthin supplementation on the antioxidant status of racing Arabian horses – preliminary study 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.
*Safety and efficacy of curcumin in the treatment of ulcerative colitis: An updated systematic review and meta-analysis of randomized controlled trials Full Text
*Impact of exercise intervention with or without curcumin supplementation on body fat composition, glucose, and lipid metabolism in obese adults: A meta-analysis

Fisetin
Nanoformulated fisetin ameliorates Alzheimer's disease via reducing proinflammatory cytokines and activating the NRF2/HO-1 pathway

Melatonin
Therapeutic effects of melatonin on the lungs of rats exposed to passive smoking Full Text
Melatonin ameliorates age-related sarcopenia by inhibiting fibrogenic conversion of satellite cell Full Text

Nicotinamide MonoNucleotide (NMN)
Nicotinamide mononucleotide protects STAT1 from oxidative stress-induced degradation to prevent colorectal tumorigenesis Full Text
*Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials Full Text
Nicotinamide mononucleotide improves the ovarian reserve of POI by inhibiting NLRP3-mediated pyroptosis of ovarian granulosa cells Full Text

Nicotinamide Riboside (NR)
*Effect of nicotinamide riboside on airway inflammation in COPD: a randomized, placebo-controlled trial Full Text
Nicotinamide Riboside Ameliorates Fructose-Induced Lipid Metabolism Disorders in Mice by Activating Browning of WAT, and May Be Also Related to the Regulation of Gut Microbiota Full Text

Resveratrol
*Effects of resveratrol supplementation on inflammatory markers, fatigue scale, fasting blood sugar and lipid profile in relapsing-remitting multiple sclerosis patients: a double-blind, randomized placebo-controlled trial
The Cognitive Restoration Effects of Resveratrol: Insight Molecular through Behavioral Studies in Various Cognitive Impairment Models Full Text
Preclinical evidence and possible mechanisms of cardioprotective effects of resveratrol in diabetic cardiomyopathy: a systematic review and meta-analysis Full Text

Other available supplements or natural substances (in alphabetical order)
Cannabidiol, a Strategy in Aging to Improve Redox State and Immunity in Male Rats Full Text
*Carnosine Supplementation Has No Effect on Inflammatory Markers in Adults with Prediabetes and Type 2 Diabetes: A Randomised Controlled Trial Full Text
The Impact of Vitamin E Supplementation on Oxidative Stress, Cognitive Functions, and Aging-Related Gene Expression in Aged Mice Full Text
*Higher Magnesium Intake Is Associated With a Lower Risk of Frailty in Older Adults
High Blood Pressure and Impaired Brain Health: Investigating the Neuroprotective Potential of Magnesium Full Text
Anti-aging natural supplements: the main players in promoting healthy lifespan Full Text

Combinations
Sex Differences in Response to Diet Enriched with Glutathione Precursors in the Aging Heart Full Text GlyNAC
*The Administration of Resveratrol and Vitamin C Reduces Oxidative Stress in Postmenopausal Women—A Pilot Randomized Clinical Trial Full Text***
*Interaction between green tea and metformin and its effects on oxidative stress and inflammation in overweight women: a randomised clinical trial Full Text
*Human Supplementation with AM3, Spermidine, and Hesperidin Enhances Immune Function, Decreases Biological Age, and Improves Oxidative–Inflammatory State: A Randomized Controlled Trial Full Text
*Metformin plus lifestyle interventions versus lifestyle interventions alone for the delay or prevention of type 2 diabetes in individuals with prediabetes: a meta-analysis of randomized controlled trials Full Text

Prescription Supplements

Metformin
Metformin: decelerates biomarkers of aging clocks Full Text
Metformin restores autophagic flux and mitochondrial function in late passage myoblast to impede age-related muscle loss Full Text
Metformin effectively alleviates the symptoms of Alzheimer in rats by lowering amyloid β deposition and enhancing the insulin signal Full Text

Miscellaneous Molecules & Prescription Drugs
*The effects of Dapagliflozin in a real-world population of HFrEF patients with different hemodynamic profiles: worse is better Full Text
*Sodium-Glucose Cotransporter 2 Inhibitors Improve Body Composition by Increasing the Skeletal Muscle Mass/Fat Mass Ratio in Patients with Type 2 Diabetes: A 52-Week Prospective Real-Life Study Full Text with Metformin
GLP-1 receptor agonists and SGLT2 inhibitors: new anti-aging tools? Full Text

Novel Molecules
Healthy longevity-associated protein improves cardiac function in murine models of cardiomyopathy with preserved ejection fraction Full Text
Lysophosphatidylethanolamine improves diastolic dysfunction by alleviating mitochondrial injury in the aging heart Full Text

Other Areas of Interest (in alphabetical order)

Ageing Clocks & other biomarkers of ageing
*Metabolite signatures of chronological age, aging, survival, and longevity Full Text
*Trends of genetic contributions on epigenetic clocks and related methylation sites with aging: A population-based adult twin study Full Text
*Estimation of physiological aging based on routine clinical biomarkers: a prospective cohort study in elderly Chinese and the UK Biobank Full Text

Exosomes (small packets of information released by cells)
Intranasal Spray Alleviates Early Alzheimer’s in Mice Full Text***
Finding Cells That Send Signals Against Arthritis Full Text***

Epigenetics & Cellular Reprogramming
Study of Direct Reprogramming Challenges Consensus Full Text CAN

Genetics including CRISPR
*FOXO3 Longevity Genotype Mitigates Risk Posed by Hypertension on Incident Coronary Artery Disease in Middle-aged Men: Kuakini Honolulu Heart Program Full Text
*Genetic variants associated with longevity in long-living Indians Full Text

Lifespan Lengthening Interventions
A small-molecule screen identifies novel aging modulators by targeting 5-HT/DA signaling pathway Full Text
The soil Mycobacterium sp. promotes health and longevity through different bacteria-derived molecules in Caenorhabditis elegans Full Text
Endogenous chondroitin extends lifespan by inhibiting VHA-7-mediated tubular lysosome formation Full Text

Microbiome
Mendelian randomization analyses support causal relationships between gut microbiome and longevity Full Text
Alleviating D-Galactose-Induced Aging in Mice by Modulating Gut-Liver Axis Using Lactiplantibacillus plantarum TY-Y10 Full Text
Gut microbiota and epigenetic age acceleration: a bi-directional Mendelian randomization study Full Text
2′-Fucosyllactose ameliorates aging-related osteoporosis by restoring gut microbial and innate immune homeostasis Full Text
Fecal Microbiota Transplantation, a tool to transfer healthy longevity Full Text

Observational Studies
*Slowed epigenetic aging in Olympic champions compared to non-champions Full Text
*The association between sleep duration trajectories and successful aging: a population-based cohort study Full Text
*Factors associated with high nutrition risk by 10-year age group: Data from the Canadian Longitudinal Study on Aging Full Text CAN
*Sociodemographic determinants of mobility decline among community-dwelling older adults: findings from the Canadian longitudinal study on ageing Full Text CAN

Opinion/Editorials/Theory/Policy
*Attitudes towards geroprotection: measuring willingness, from lifestyle changes to drug use Full Text
A scenario for an evolutionary selection of ageing Full Text
Digital Doppelgängers and Lifespan Extension: What Matters? Full Text
The Epistemic Policies of Anti-Ageing Medicines in the European Union Full Text
Promoting the Concept Healthy Ageing for Use in Gerontological Health and Social Care Policy and Practice Full Text

Other Ageing Biology
Negative effects of lifespan extending intervention on resilience in mice Full Text
Elevated glucose levels increase vascular calcification risk by disrupting extracellular pyrophosphate metabolism Full Text
Isolating the direct effects of growth hormone on lifespan and metabolism in mice Full Text

Reproductive Health
Stem cell transplantation extends the reproductive life span of naturally aging cynomolgus monkeys Full Text***
*The role of anti-aging approaches in managing hypogonadism in sedentary older males Full Text
Building an Atlas of Human Ovarian Aging Full Text

Reviews
*The effect of altered sleep timing on glycaemic outcomes: Systematic review of human intervention studies Full Text CAN
The Quest for Eternal Youth: Hallmarks of Aging and Rejuvenating Therapeutic Strategies Full Text
The mitochondrial integrated stress response: A novel approach to anti-aging and pro-longevity Full Text

Senolytics/Senescent Cells
Restoration of hair follicle inductive properties by depletion of senescent cells Full Text

Skin & Beauty
*TFC-1326 Compound Reduces Clinical Signs of Skin Aging. Evidence From In Vitro Human Adipose and Skin Models and Pilot Clinical Trial Full Text
*The Role of Cacao Powder in Enhancing Skin Moisture and Reducing Wrinkles: A 12-Week Clinical Trial and In Vitro Study Full Text
Comparing the Effectiveness of Platelet-Rich Plasma Alone Versus Combined With Microneedles or Radiofrequency for Neck Wrinkle Treatment Full Text

Stem Cells
*World-first stem-cell treatment restores vision in people Full Text***
Human-induced pluripotent stem cell-derived microglia integrate into mouse retina and recapitulate features of endogenous microglia Full Text
*Clinical outcomes of autologous adipose-derived mesenchymal stem cell combined with high tibial osteotomy for knee osteoarthritis are correlated with stem cell stemness and senescence Full Text

Telomeres
Influence of diet and exercise on leukocyte telomere length, markers of oxidative stress and inflammation in rats Full Text

Odds & Sods
Predation affects the evolution of sex-specific longevity Full Text
*Cannabis Use and Age-Related Changes in Cognitive Function From Early Adulthood to Late Midlife in 5162 Danish Men Full Text
Convergent evolution associated with the loss of developmental diapause may promote extended lifespan in bees Full Text
Oxidative Stress in an African Ground Squirrel, a Case of Healthy Aging and Reproduction 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.*
--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

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

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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 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