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February 2025 Longevity Review
longevity omega 3 vitamin d exercise klotho gene therapy cellular rejuvenation young plasma
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!
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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
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)
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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