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.
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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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