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May 2024 Longevity Review

Posted by Chris Pollyanna , 30 June 2024 · 430 views

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As we transition towards summer you will find in this month’s Longevity Review, a study showing that senolytics might already be in widespread use; further proof of the mortality benefits of the Mediterranean diet; a Canadian study showing how increased protein intake boosts muscle building in the elderly; news from a longevity conference and a heavyweight debate on the path forward for longevity.
In the supplemental section you will find in Fasting, how intermittent fasting improves gut health; in Exercise, how exercise acts as a senolytic; in Combinations, a pair of studies showing synergistic effects between vitamin D intake and physical activity; in Genetics, a gene therapy for dementia; in Lifespan, the latest Interventions Testing Program results; in Other Ageing Biology, how the naked mole rat continues to defy the law of mortality; in Skin & Beauty, successful skin care trials; in Stem Cells, a therapy for low grade inflammation; and in Odds & Sods, more studies on the benefits of hyperbaric oxygen therapy. And, of course, much more!

Canadian Longevity Association News

We had our first in-person event of the year, with a longevity walk along the boardwalk in Toronto. Although the weather didn’t start off being cooperative, by the time the walk started, the heavens had cleared and it turned out to be nice and sunny so that good times were had by all.
We also had another volunteer join our ever expanding team - welcome Mike Cottrill!

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May 2024 Round-Up:

Are millions of people already taking senolytics? That is the intriguing question posed by this paper which posits that SGLT2 inhibitors, used to treat diabetes, heart failure and chronic kidney disease, also act as an indirect senolytic. The evidence appears to be that this is true, which opens up the possibility of expanding their indications to treat aging more generally.
SGLT2 inhibition eliminates senescent cells and alleviates pathological aging Full Text

By now we should all be aware of the health benefits of the Mediterranean diet, with countless studies to back up that claim. However, most of those studies were over short timeframes, not exceeding a few years. This study, on the other hand, tracked 25K women over 25 years and found that those who more closely followed the diet had a 23% lower risk of mortality than those who didn’t.
*Mediterranean Diet Adherence and Risk of All-Cause Mortality in Women Full Text

One of the first major longevity conferences of the year, the Rejuvenation Startup Summit, took place in Berlin in May, with numerous talks from researchers and biotechs working on longevity. You can read more about it in this detailed write up from Lifespan.io. You can also check out the videos of the talks, which have begun to be posted on YouTube.
“Everything Happens in Berlin”: Highlights from the Summit
Rejuvenation Startup Summit Videos

There was also a highly anticipated debate between Aubrey de Grey and Peter Fedichev, over the best strategy to defeat aging with (in simplistic terms) Aubrey arguing for reversal, while Peter argued for a halting of the aging process. There was a $10K prize for the winner.
How to Defeat Aging? Two Scientists Offer Their Visions
Debate Video

Canadian Content Study

The importance of having enough muscle mass when you age cannot be overstated - the lower the muscle mass, the greater the risk of frailty and ultimately, mortality. But, how to achieve that? Apart from resistance training, adequate protein intake is essential. In fact, older people need substantially more than younger adults as they don’t synthesize it as effectively.

This study, from McMaster University, looked at giving older men an additional 50 grams of protein over the recommended daily amount (0.8g/kg) in the form of whey, pea or collagen protein to be consumed over breakfast and lunch. This resulted in a 9% increase in protein synthesis for both whey and pea protein, but not for collagen.
*The effects of whey, pea, and collagen protein supplementation beyond the recommended dietary allowance on integrated myofibrillar protein synthetic rates in older males: a randomized controlled trial Full Text

Other Canadian studies can be found marked as CAN throughout this newsletter.

Supplemental Section

Lifestyle
*Protein Intake and Physical Activity Levels as Determinants of Sarcopenia Risk in Community-Dwelling Older Adults Full Text
*Epigenetic Age Mediates the Association of Life's Essential 8 With Cardiovascular Disease and Mortality Full Text
*Physical activity and fiber intake beneficial for muscle mass and strength preservation during aging: A comprehensive cross-sectional study in the UK biobank cohort Full Text

Fasting/Dietary Restriction – certainly the cheapest & also one of the most effective anti-ageing interventions currently available. It comes in many flavours, but I fast for at least 12 hours every day.
*Intermittent fasting shows promise in improving gut health, weight management Full Text
Intermittent fasting protects against liver inflammation and liver cancer Full Text
*Effect of time-restricted eating and intermittent fasting on cognitive function and mental health in older adults: A systematic review Full Text

Diet – let food be thy medicine…
*Dietary protein and amino acid intakes for mitigating sarcopenia in humans Full Text
*Association of coffee and tea consumption with osteoporosis risk: A prospective study from the UK biobank
*Effect of Food Groups on Aging in Older Women
*Identifying the relation between food groups and biological ageing: a data-driven approach Full Text

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*Exercise May Remove Senescent Cells Through Inflammation Full Text
*Effects of physical exercise on neuromuscular junction degeneration during ageing: A systematic review Full Text
Potential molecular mechanism of exercise reversing insulin resistance and improving neurodegenerative diseases Full Text

Non-prescription Supplements (in alphabetical order)
NOTE - the supplements selected below are not exhaustive. They reflect what I thought were the most interesting ones back in 2019, with only a few updates since. I do individual searches for each and simply do not have time to do all others. Additionally, I’ve noticed how a lot of natural supplements affect the same genetic pathways, so I think that there is a lot of overlap and redundancy.

Astaxanthin – which is behind the pink colour of salmon & shrimp. Considered the most powerful carotenoid, it has anti-oxidative, anti-inflammatory, anti-cancer, neuro-protective and skin-protective qualities.
*Comparative Pharmacokinetic Study of Standard Astaxanthin and its Micellar Formulation in Healthy Male Volunteers Full Text
Protective effects of astaxanthin on particulate matter 2.5‑induced senescence in HaCaT keratinocytes via maintenance of redox homeostasis Full Text

Curcumin – the spice which gives curries their yellow colour. Anti-inflammatory and neuroprotective. Needs to be taken with black pepper (piperine) to improve bioavailability.
*Effect of nano-curcumin supplementation on angina status, and traditional and novel cardiovascular risk factors in overweight or obese patients with coronary slow flow phenomenon: a randomized double-blind placebo-controlled clinical trial Full Text
*Effects of curcumin in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis Full Text

Fisetin
*Clinical validation of C12FDG as a marker associated with senescence and osteoarthritic phenotypes Full Text

Melatonin
Melatonin promotes hair regeneration by modulating the Wnt/β-catenin signalling pathway Full Text
*Clinical Studies Using Topical Melatonin Full Text

Nicotinamide MonoNucleotide (NMN)
Integrated transcriptome and metabolome study reveal the therapeutic effects of nicotinamide riboside and nicotinamide mononucleotide on nonalcoholic fatty liver disease Full Text & NR
Toxicology study profile of Nicotinamide mononucleotide after acute and 90-day sub chronic dosing in Wistar rats and mutagenicity tests Full Text
*Ingestion of β-nicotinamide mononucleotide increased blood NAD levels, maintained walking speed, and improved sleep quality in older adults in a double-blind randomized, placebo-controlled study

Nicotinamide Riboside (NR)
Nicotinamide riboside attenuates myocardial ischemia-reperfusion injury via regulating SIRT3/SOD2 signaling pathway Full Text
Hepatic steatosis induced by nicotine plus Coca-Cola™ is prevented by nicotinamide riboside (NR) Full Text

Resveratrol
SIRT1, resveratrol and aging Full Text

Other available supplements or natural substances (in alphabetical order)
Potential Effects of Traditional Chinese Medicine in Anti-Aging and Aging-Related Diseases: Current Evidence and Perspectives Full Text
Real-world Chinese herbal medicine for Parkinson's disease: a hospital-based retrospective analysis of electronic medical records Full Text
*Emerging Roles of Vitamin B12 in Aging and Inflammation Full Text
The evidence to date: implications of l-ascorbic acid in the pathophysiology of aging Full Text
Why One Antioxidant Might Alleviate Disc Degeneration Full Text
Quercetin promotes the proportion and maturation of NK cells by binding to MYH9 and improves cognitive functions in aged mice Full Text
*The effects of omega-3 polyunsaturated fatty acids on muscle and whole-body protein synthesis: a systematic review and meta-analysis Full Text
Urolithin A improves Alzheimer's disease cognition and restores mitophagy and lysosomal functions Full Text

Combinations
*Synergistic impact of 25-hydroxyvitamin D concentrations and physical activity on delaying aging Full Text
*Association of physical activity and vitamin D deficiency with cognitive impairment in older adults: a population based cross-sectional analysis Full Text
A cocktail of rapamycin, acarbose, and phenylbutyrate prevents age-related cognitive decline in mice by targeting multiple aging pathways Full Text
Docosahexaenoic Acid (DHA), Vitamin D3, and Probiotics Supplementation Improve Memory, Glial Reactivity, and Oxidative Stress Biomarkers in an Aluminum-Induced Cognitive Impairment Rat Model Full Text
A randomized, controlled clinical trial demonstrates improved owner-assessed cognitive function in senior dogs receiving a senolytic and NAD+ precursor combination Full Text

Prescription Supplements

Metformin
*Metformin mitigates dementia risk among individuals with type 2 diabetes Full Text

Rapamycin (sirolimus)
Inhibition of mTOR prevents glucotoxicity-mediated increase of SA-beta-gal, p16INK4a, and insulin hypersecretion, without restoring electrical features of mouse pancreatic islets Full Text

Miscellaneous Molecules & Prescription Drugs
Intermittent glucocorticoid treatment improves muscle metabolism via the PGC1α/Lipin1 axis in an aging-related sarcopenia model Full Text
Hydroxycitrate delays early mortality in mice and promotes muscle regeneration while inducing a rich hepatic energetic status Full Text
SGLT2 inhibition to target kidney aging Full Text
Hypothalamic sex-specific metabolic shift by canagliflozin during aging Full Text

Novel Molecules
Small-molecule-induced epigenetic rejuvenation promotes SREBP condensation and overcomes barriers to CNS myelin regeneration

Other Areas of Interest (in alphabetical order)

Ageing Clocks & other biomarkers of ageing
How biological aging clocks tick Full Text
Quantifying the stochastic component of epigenetic aging Full Text
*Proteomic aging clock (PAC) predicts age-related outcomes in middle-aged and older adults Full Text
*The effect of epigenetic aging on neurodegenerative diseases: a Mendelian randomization study Full Text

Blood Factors or other Heterochronic Transplantation
Young blood-mediated cerebromicrovascular rejuvenation through heterochronic parabiosis: enhancing blood-brain barrier integrity and capillarization in the aged mouse brain
Long-term hematopoietic transfer of the anti-cancer and lifespan-extending capabilities of a genetically engineered blood system by transplantation of bone marrow mononuclear cells Full Text

Epigenetics & Cellular Reprogramming
A youthful touch: Reversal of aging hallmarks by cell reprogramming Full Text

Exosomes (small packets of information released by cells)
Strategies in product engineering of mesenchymal stem cell-derived exosomes: unveiling the mechanisms underpinning the promotive effects of mesenchymal stem cell-derived exosomes Full Tex
Mesenchymal Stem Cells-based Cell-free Therapy Targeting Neuroinflammation Full Text

Genetics including CRISPR
Emerging technology has a brilliant future: the CRISPR-Cas system for senescence, inflammation, and cartilage repair in osteoarthritis Full Text
*Progranulin AAV gene therapy for frontotemporal dementia: translational studies and phase 1/2 trial interim results Full Text
*Genetic effects and causal association analyses of 14 common conditions/diseases in multimorbidity patterns Full Text

Lifespan Lengthening Interventions
Lifespan effects in male UM-HET3 mice treated with sodium thiosulfate, 16-hydroxyestriol, and late-start canagliflozin
Targeting CK2 eliminates senescent cells and prolongs lifespan in Zmpste24-deficient mice Full Text
Translatability of life-extending pharmacological treatments between different species Full Text
Low-dose naltrexone extends healthspan and lifespan in C. elegans via SKN-1 activation Full Text

Microbiome
Enhancing probiotic impact: engineering Saccharomyces boulardii for optimal acetic acid production and gastric passage tolerance Full Text
Oral Administration of Bifidobacterium lactis Ameliorates Cognitive Deficits in Mice Intracerebroventricularly Administered Amyloid Beta via Regulation the Activation of Mitogen-activated Protein Kinases Full Text
*Association of the oral microbiome with cognitive function among older adults: NHANES 2011–2012 Full Text

Observational Studies
*Arthritis is associated with high nutritional risk among older Canadian adults from the Canadian Longitudinal Study on Aging Full Text CAN
*Short communication: Lifetime musical activity and resting-state functional connectivity in cognitive networks Full Text
*Circulating microRNA profile of long-lived Okinawans identifies novel potential targets for optimizing lifespan and health span Full Text
*Predictive values of relative fat mass and body mass index on cardiovascular health in community-dwelling older adults: Results from the Longevity Check-up (Lookup) 7+ Full Text

Opinion/Editorials/Theory
Gerogenes and gerosuppression: the pillars of precision geromedicine Full Text May
The beginning of becoming a human Full Text
Successful Aging and Subjective Aging: Toward a Framework to Research a Neglected Connection Full Text
Psychogenic Aging: A Novel Prospect to Integrate Psychobiological Hallmarks of Aging Full Text

Other Ageing Biology
Identification and characterization of small molecule inhibitors of the LINE-1 retrotransposon endonuclease Full Text
Intracellular cytokines in peritoneal leukocytes relate to lifespan in aging and long-lived female mice Full Text
Trio preserves motor synapses and prolongs motor ability during aging Full Text
Five years later, with double the demographic data, naked mole-rat mortality rates continue to defy Gompertzian laws by not increasing with age Full Text

Reproductive Health
*Examining the Effects of Nutrient Supplementation on Metabolic Pathways via Mitochondrial Ferredoxin in Aging Ovaries Full Text
Expert Consensus on Prevention and Treatment of Aging-Related Gonadal Dysfunction Full Text
Preservation of ovarian function using human pluripotent stem cell-derived mesenchymal progenitor cells Full Text
*The efficacy of oral Lavandula angustifolia Mill. essential oil on menopausal symptoms, serum lipid profile, and cortisol concentration in postmenopausal women: A triple-blind, randomized, controlled trial Full Text

Reviews
Impact of Aging on Cardiovascular Diseases: From Chronological Observation to Biological Insights: JACC Family Series Full Text
Molecular mechanisms of aging and anti-aging strategies Full Text
Physical Activity and Oxidative Stress in Aging Full Text

Senolytics/Senescent Cells
Senolytics and cell senescence: historical and evolutionary perspectives Full Text
Senolytic combination of dasatinib and quercetin attenuates renal damage in diabetic kidney disease Full Text
Failure of senolytic treatment to prevent cognitive decline in a female rodent model of aging Full Text
The potential for senotherapy as a novel approach to extend life quality in veterinary medicine Full Text

Skin & Beauty
*Anti-aging Effects of Tirbanibulin 1% Ointment: A Real-Life Experience Full Text
*Beneficial Effects of Multi-Micronutrient Supplementation with Collagen Peptides on Global Wrinkles, Skin Elasticity and Appearance in Healthy Female Subjects Full Text
*Low-level laser therapy for skin rejuvenation: A safe and effective solution baked by data and visual evidence Full Text

Stem Cells
*Safety and efficacy of autologous adipose tissue-derived stem cell transplantation in aging-related low-grade inflammation patients: a single-group, open-label, phase I clinical trial Full Text
Dental pulp stem cells ameliorate D-galactose-induced cardiac ageing in rats Full Text
Rejuvenation of peripheral immune cells attenuates Alzheimer’s disease-like pathologies and behavioral deficits in a mouse model Full Text

Telomeres
Elevated tissue status of omega-3 fatty acids protects against age-related telomere attrition in fat-1 transgenic mice Full Text

**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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