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April 2024 Longevity Review
longevity supplements lifestyle stem cells extracellular vesicles nmn nad+ astaxanthin rapamycin curcumin
In this month’s Longevity Review you will find how small extracellular vesicles, which cells use to communicate with each other, can increase lifespan in mice; how stem cells taken from umbilical cords can help with frailty in humans; the best time of day to exercise to reduce your mortality if you suffer from obesity or diabetes; and, in the Canadian Content section, how the nuclear envelope is more dynamic than initially thought, and helps repair DNA damage.
In the supplemental section you will find, under exercise, the effects of different intensities of resistance training; in additional supplements, two reviews of vitamin D and one of magnesium; in opinion an interesting piece on how we need a new discipline of juventology; in reproduction, a number of ways to delay Ovarian aging using stem cells, NMN, NR & quercetin; and, in stem cells, how transplanting mitochondria can improve muscle function. In addition, there are a record six Canadian studies in this edition, marked by CAN. Plus of course much more!
Canadian Longevity Association News
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April 2024 Round-Up:
In this study, small extracellular vesicles (sEVs)(small packets of chemical information cells use to communicate with each other) from young male mice extended the average lifespan of old male mice by 12% - a considerable amount considering treatment only started in old age. In addition, various physiological functions improved, including fertility. Additionally, this treatment seemed to cross the species barrier as sEVs taken from younger human males had a similar effect on the mice, which indicates, if the reverse held true, that we might be able to get an abundant source of young sEVs from farm animals for example.
Young Extracellular Vesicles Extend Life in Old Mice Full Text
Further showing the potential of sEVs and their ilk, this small human study of umbilical cord stem cells improved various parameters of frailty in elderly Chinese, which improved their quality of life. I link this to sEVs as the main benefit of stem cells derives from the substances they excrete, sEVs among them, as the cells themselves do not last long in the body.
*Stem Cells Alleviate Frailty in Clinical Trial Full Text
Here is a very actionable association study using data from the UK Biobank. For older people with obesity, the best time of day to perform moderate to vigorous physical activity was in the evenings, with a whopping 61% reduction in mortality compared to those who did not exercise. This was considerably better than exercising in the morning or afternoon, though any time of day is better than none.
*Evening Aerobic Exercise Associated with Least Mortality Full Text
Canadian Content Highlight
In this groundbreaking study from the lab of University of Toronto professor Dr. Karim Mekhail, they showed that the envelope which surrounds the nucleus in our cells is actively involved in the repair of DNA damage. Although this paper mainly concentrates on the effects on cancer, they also briefly touch on progeria and by extension, aging. The lab is actively pursuing studies related to this on aging, including means to reverse changes to the envelope with age.
Toronto researchers uncover human DNA repair by nuclear metamorphosis
Team effort reveals cells reshape their nucleus to repair DNA, impacting cancer and aging
DNA double-strand break–capturing nuclear envelope tubules drive DNA repair Abstract
Full Text
Supplemental Section
Lifestyle
*Protein-enriched soup and weekly exercise improve muscle health: A randomized trial in mid-to-old age with inadequate protein intake Full Text
*Association between Life’s Essential 8 and cognitive function: insights from NHANES 2011–2014 Full Text
*Lifestyle-related factors in late midlife as predictors of frailty from late midlife into old age: a longitudinal birth cohort study Full Text
Fasting/Dietary Restriction – certainly the cheapest & also one of the most effective anti-ageing interventions currently available. It comes in many flavours, but I fast for at least 12 hours every day.
*Effect of calorie restriction and intermittent fasting on glucose homeostasis, lipid profile, inflammatory, and hormonal markers in patients with polycystic ovary syndrome: a systematic review Full Text
*Neuroprotective effects of intermittent fasting in the aging brain Full Text
*Effect of Isocaloric, Time-Restricted Eating on Body Weight in Adults With Obesity: A Randomized Controlled Trial
Diet – let food be thy medicine…
*The association of the dietary inflammatory potential with risk of overall and site-specific cancers: A community-based longitudinal study in the UK Biobank Full Text
*Wild Blueberry Extract Intervention in Healthy Older Adults: A Multi-Study, Randomised, Controlled Investigation of Acute Cognitive and Cardiovascular Effects Full Text
*Alcohol consumption and accelerated biological ageing in middle-aged and older people: A longitudinal study from two cohorts
Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*Effect of resistance circuit training on comprehensive health indicators in older adults: a systematic review and meta-analysis Full Text
*Presence of specific lipids indicate tissue ageing and can be decreased through exercise Full Text
Non-prescription Supplements (in alphabetical order)
NOTE - the supplements selected below are not exhaustive. They reflect what I thought were the most interesting ones back in 2019, with only a few updates since. I do individual searches for each and simply do not have time to do all others. Additionally, I’ve noticed how a lot of natural supplements affect the same genetic pathways, so I think that there is a lot of overlap and redundancy.
Astaxanthin – which is behind the pink colour of salmon & shrimp. Considered the most powerful carotenoid, it has anti-oxidative, anti-inflammatory, anti-cancer, neuro-protective and skin-protective qualities.
Astaxanthin prevents bone loss in osteoporotic rats with palmitic acid through suppressing oxidative stress Full Text
Nrf2 Plays a Key Role in Erythropoiesis during Aging Full Text
Curcumin – the spice which gives curries their yellow colour. Anti-inflammatory and neuroprotective. Needs to be taken with black pepper (piperine) to improve bioavailability.
*Patient-reported outcomes of curcumin supplementation in rheumatoid arthritis and psoriatic arthritis: a cross-sectional survey
*The efficacy of curcumin in relieving osteoarthritis: A meta-analysis of meta-analyses
Advancing Gastrointestinal Health: Curcumin’s Efficacy and Nanopreparations Full Text
Curcumin attenuates brain aging by reducing apoptosis and oxidative stress
*Curcumin as a Multifunctional Spice Ingredient against Mental Disorders in Humans: Current Clinical Studies and Bioavailability Concerns Full Text
Melatonin
A Clinical, Pharmacological, and Formulation Evaluation of Melatonin in the Treatment of Ocular Disorders—A Systematic Review Full Text
*The Positive Association between Melatonin-Containing Food Consumption and Older Adult Life Satisfaction, Psychoemotional State, and Cognitive Function Full Text
Antioxidant Actions of Melatonin: A Systematic Review of Animal Studies Full Text
Nicotinamide MonoNucleotide (NMN)
A Magnesium Binding Site And The Anomeric Effect Regulate The Abiotic Redox Chemistry Of Nicotinamide Nucleotides Full Text CAN
LXR/CD38 activation drives cholesterol-induced macrophage senescence and neurodegeneration via NAD+ depletion Full Text
Pterostilbene
Pterostilbene Protects against Osteoarthritis through NLRP3 Inflammasome Inactivation and Improves Gut Microbiota as Evidenced by In Vivo and In Vitro Studies Full Text
Resveratrol
Resveratrol alleviates acute lung injury in mice by promoting Pink1/Parkin-related mitophagy and inhibiting NLRP3 inflammasome activation Full Text
Exploring the multimodal health-promoting properties of resveratrol: A comprehensive review Full Text
Potential role of resveratrol in prevention and therapy of diabetic complications: a critical review Full Text
Other available supplements or natural substances (in alphabetical order)
Comparing the efficacy of concomitant treatment of resistance exercise and creatine monohydrate versus multiple individual therapies in age related sarcopenia Full Text
*Consensus Statement on Vitamin D Status Assessment and Supplementation: Whys, Whens, and Hows Full Text
*The Power of Vitamin D: Is the Future in Precision Nutrition through Personalized Supplementation Plans? Full Text
L-Ergothioneine slows the progression of age-related hearing loss in CBA/CaJ mice
Association between dietary magnesium intake, inflammation, and neurodegeneration Full Text
*The efficacy and safety of Nigella sativa in the management of osteoarthritis: A systematic review Full Text
*Improvement in Visceral Adipose Tissue and LDL Cholesterol by High PUFA Intake: 1-Year Results of the NutriAct Trial Full Text
Methylated urolithin A, mitigates cognitive impairment by inhibiting NLRP3 inflammasome and ameliorating mitochondrial dysfunction in aging mice
Combinations
*The effect of curcumin and high-content eicosapentaenoic acid supplementations in type 2 diabetes mellitus patients: a double-blinded randomized clinical trial Full Text
*Effects of vitamin D3, omega-3 s and a simple strength training exercise program on bone health: the DO-HEALTH randomized controlled trial Full Text
Combined Metabolic Activators with Different NAD+ Precursors Improve Metabolic Functions in the Animal Models of Neurodegenerative Diseases Full Text
Prescription Supplements
Metformin
Causal association of metformin treatment with diverse cardiovascular diseases: a Mendelian randomization analysis Full Text
Rapamycin (sirolimus)
*Evaluating the effect of rapamycin treatment in Alzheimer’s disease and aging using in vivo imaging: the ERAP phase IIa clinical study protocol Full Text
Effect and Mechanism of Rapamycin on Cognitive Deficits in Animal Models of Alzheimer's Disease: A Systematic Review and Meta-analysis of Preclinical Studies
Miscellaneous Molecules & Prescription Drugs
Transcriptome-based deep learning analysis identifies drug candidates targeting protein synthesis and autophagy for the treatment of muscle wasting disorder Full Text
Canagliflozin inhibits PASMCs proliferation via regulating SGLT1/AMPK signaling and attenuates artery remodeling in MCT-induced pulmonary arterial hypertension Full Text
Itaconate alleviates anesthesia/surgery-induced cognitive impairment by activating a Nrf2-dependent anti-neuroinflammation and neurogenesis via gut-brain axis Full Text
Doxycycline decelerates aging in progeria mice Full Text
GLP-2 ameliorates D-galactose induced muscle aging by IGF-1/Pi3k/Akt/FoxO3a signaling pathway in C2C12 cells and mice Full Text
Other Areas of Interest (in alphabetical order)
Ageing Clocks & other biomarkers of ageing
*Aging Measurements Can Vary by Time of Day Full Text
*A Comparison of 5 Measures of Accelerated Biological Aging and Their Association With Incident Cardiovascular Disease: The CARDIA Study Full Text
*Accelerated epigenetic age is associated with whole-brain functional connectivity and impaired cognitive performance in older adults Full Text
Epigenetics & Cellular Reprogramming
Nonlinear DNA methylation trajectories in aging male mice Full Text
*Very Long-Lived People Have Protected Epigenetics
*Methylation entropy landscape of Chinese long-lived individuals reveals lower epigenetic noise related to human healthy aging Full Text
Exosomes (small packets of information released by cells)
Stem cell secretome treatment improves whole-body metabolism, reduces adiposity, and promotes skeletal muscle function in aged mice Full Text
The complexity of extracellular vesicles: Bridging the gap between cellular communication and neuropathology Full Text CAN
Young osteocyte-derived extracellular vesicles facilitate osteogenesis by transferring tropomyosin-1 Full Text
Genetics including CRISPR
*Cognitively healthy centenarians are genetically protected against Alzheimer's disease Full Text
*Polygenic markers of survival and longevity in the antioxidant genes PON1, PON2, MTHFR, MSRA, SOD1, NQO1, and CAT in a 20-year follow-up study in the population from the Volga-Ural region
Lifespan Lengthening Interventions
Low-Molecular Weight Compounds that Extend the Chronological Lifespan of Yeasts, Saccharomyces cerevisiae, and Schizosaccharomyces pombe Full Text
A Re-Analysis Finds Potential Life-Prolonging Compounds Full Text
Microbiome
*Oral microbial signatures associated with age and frailty in Canadian adults Full Text CAN
Polyphenolic Compounds: Orchestrating Intestinal Microbiota Harmony during Aging Full Text
*Age and aging process alter the gut microbes Full Text
Observational Studies
*Associations Between Age at Menopause, Vascular Risk, and 3-Year Cognitive Change in the Canadian Longitudinal Study on Aging CAN
*Serum klotho levels and mortality patterns in frail individuals: unraveling the u-shaped association Full Text
*The prognostic value of serum α-klotho in age-related diseases among the US population: A prospective population-based cohort study Full Text
*Systolic Blood Pressure and Survival to Very Old Age: Results From the Women’s Health Initiative Full Text
*Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021 Full Text
*People think 'old age' starts later than it used to, study finds Abstract
Opinion/Editorials/Theory
Exploring juventology: unlocking the secrets of youthspan and longevity programs Full Text
Ageing as a two-phase process: theoretical framework Full Text
NIA Translational Geroscience Network: An infrastructure to facilitate geroscience-guided clinical trials Full Text
Other Ageing Biology
Identification of prospective aging drug targets via Mendelian randomization analysis Full Text
The coupling between healthspan and lifespan in Caenorhabditis depends on complex interactions between compound intervention and genetic background Full Text
Predictive Models of Life Span in Old Female Mice Based on Immune, Redox, and Behavioral Parameters Full Text
Mitochondria Injection Alleviates Parkinson’s in Mice
Mitochondrial transplantation exhibits neuroprotective effects and improves behavioral deficits in an animal model of Parkinson's disease Full Text
Regenerative Medicine
Regeneration of Nonhuman Primate Hearts With Human Induced Pluripotent Stem Cell–Derived Cardiac Spheroids Full Text
Reproductive Health
Efficacy and safety of mesenchymal stem cell therapy for ovarian ageing in a mouse model Full Text
NMN and NR Reverse Ovarian Aging in Rats Full Text
*The impact of resveratrol on the outcome of the in vitro fertilization: an exploratory randomized placebo-controlled trial Full Text
Quercetin Delays Ovarian Aging in Middle-Aged Mice Full Text
Reviews
Genetic, Environmental, and Stochastic Components of Lifespan Variability: The Drosophila Paradigm Full Text
Will cellular immunotherapies end neurodegenerative diseases? Full Text
How does a fly die? Insights into ageing from the pathophysiology of Drosophila mortality Full Text
Senolytics/Senescent Cells
Chemical Strategies for the Detection and Elimination of Senescent Cells Full Text
Senescence and senolysis in cancer: The latest findings Full Text
Cellular Senescence as a Targetable Risk Factor for Cardiovascular Diseases: Therapeutic Implications: JACC Family Series Full Text
Skin & Beauty
Discovery of a novel and highly selective JAK3 inhibitor as a potent hair growth promoter Full Text
*Exosomes and Signaling Nanovesicles from the Nanofiltration of Preconditioned Adipose Tissue with Skin-B® in Tissue Regeneration and Antiaging: A Clinical Study and Case Report Full Text
*Use of platelet rich plasma for skin rejuvenation Full Text
Stem Cells
Rebuilding and rebooting immunity with stem cells Full Text CAN
Transplanting Mitochondria Improves Muscle Function Full Text
The Effect of Short-Term NAD3® Supplementation on Circulating Adult Stem Cells in Healthy Individuals Aged 40-70 Years Full Text
Telomeres
*Telomeres and aging: on and off the planet! Full Text
New insights from bidirectional Mendelian randomization: causal relationships between telomere length and mitochondrial DNA copy number in aging biomarkers Full Text
*Genetic susceptibility to chronic diseases leads to heart failure among Europeans: the influence of leukocyte telomere length Full Text
Odds & Sods
Hyperbaric oxygen therapy promotes the browning of white fat and contributes to the healing of diabetic wounds Full Text
*Cannabis smoking is associated with advanced epigenetic age Full Text
FNDC5/irisin mediates the protective effects of Innovative theta-shaking exercise on mouse memory Full Text
*Effect of whole-body vibration stimulation on plasma soluble TNF receptors in elderly with sarcopenia: a randomized controlled trial Full Text
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***Disclaimer 1 – I am NOT a doctor or indeed a scientist. All the information pertained within is for information purposes only; use at your own risk. Please consult with a healthcare practitioner if you need medical advice.***
**Disclaimer 2 – In no way should supplements be a replacement for an unhealthy diet or lifestyle. A varied, plant dominant dietary pattern is the cornerstone for health. Try to eat the rainbow – the greater the variety, the greater the benefit. Even though I might take a supplement derived from a plant source, I still eat the plant in question. Also, make sure you move as much as possible – that is what we evolved to do.**
*Also bear in mind that most of the studies mentioned above are in rodents, not humans. Rodents, needless to say, do not always react the same way to drugs as humans do – witness the countless times cancer or another disease has been cured in rodents only to subsequently fail human trials. I have *starred any human trials.*
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