January 2024 Longevity Review

Kicking off the new year with a bevy of interesting longevity research including the intriguing possibility of lifelong protection against senescent cells, harnessing the immune system’s pathogen response to treat ageing, using rapamycin to encourage hair growth, and, in a new addition focusing on Canadian researchers working on longevity, a novel compound which shows potential to rapidly reverse certain aspects of ageing.

In the supplemental section you will find a scoping review of intermittent fasting, a study making me reconsider my aversion to taking a multivitamin, how brain to fat tissue communication increases mouse lifespan, and three general reviews of anti-ageing interventions, plus of course much more!

In addition, and in light of a greater focus on Canadian longevity research (we are the CLA after all), any Canadian research making the grade of this newsletter will be denoted by a CAN after the link.

And in a little bit of housekeeping news, I’ve made a few changes to how these newsletters and videos are put together, including finally getting a video editor instead of relying on YouTube’s inbuilt version (I know, I know!), so that they are easier to produce and should come out in a more timely manner henceforth.

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January 2024 Highlights:

This paper is not the first time that CAR T cells, which have been successfully deployed against blood cancers, have been repurposed to clear senescent cells from a mouse. However, this is the first time that they have shown the same persistence as seen in cancer, leading to the possibility of a “once and done” treatment for senescent cells. This treatment also prevented mice from developing metabolic syndrome on a high fat diet.
The fountain of youth is ... a T cell? CAR T Therapy Lowers Senescence, Improves Health in Mice Lifespan,io Reveiw Full Text

Researchers in this paper discovered that activating an immune system receptor led to life extension in mice ( and improvement in various physiological parameters. A quite impressive result which brings up the possibility of modulating the immune system to improve longevity.
Mucosal TLR5 activation controls healthspan and longevity Full Text

Although primarily concerned with basic biology, this paper is sure to interest those who are, shall we say, “follically challenged”, as it shows that not only is autophagy needed for hair growth in mice, but that rapamycin, as an autophagy activator, greatly encourages it. This seems very readily translatable to humans.
Rapamycin Rescues Hair Growth in Mice Full Text

Canadian Research Highlight - longevity research involving Canadian researchers, wholly or in part:

An in silico screen of molecules against a genetic longevity database brought up a novel compound which showed potential for reversing certain aspects of ageing in the kidney, brain and hearts of mice. With contributions from the University of Ottawa researchers.
HDAC1/2 inhibitor therapy improves multiple organ systems in aged mice Full Text

Supplemental Section

Lifestyle
*The combination of physical activity with fruit and vegetable intake associated with life satisfaction among middle-aged and older adults: a 16-year population-based cohort study Full Text
*Life’s Essential 8 in relation to self-rated health and health-related quality of life in a large population-based sample: the SCAPIS project Full Text
*Effectiveness of a combined lifestyle intervention for older people in long-term care: A randomized controlled 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.
*What Time-Restricted Eating Does and Doesn’t Affect Full Text
*Impact of Intermittent Fasting and/or Caloric Restriction on Aging-Related Outcomes in Adults: A Scoping Review of Randomized Controlled Trials Full Text
*Effect of Calorie Restriction and Intermittent Fasting Regimens on Brain-Derived Neurotrophic Factor Levels and Cognitive Function in Humans: A Systematic Review Full Text

Diet – let food be thy medicine…
*High Tyrosol and Hydroxytyrosol Intake Reduces Arterial Inflammation and Atherosclerotic Lesion Microcalcification in Healthy Older Populations Full Text CAN
*Composite dietary antioxidant index associated with delayed biological aging: a population-based study Full Text
*Metabolome biomarkers linking dietary fibre intake with cardiometabolic effects: results from the Danish Diet, Cancer and Health-Next Generations MAX study Full Text

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*How Cardiovascular Mortality Goes Down with Exercise Full Text
*New research finds half-cardio, half-strength training reduces cardiovascular disease risks Full Text
*High‐Intensity Interval Training Is Associated With Improved 10‐Year Survival by Mediating Left Ventricular Remodeling in Patients With Heart Failure With Reduced and Mid‐Range Ejection Fraction 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.
*Effects of Astaxanthin Supplementation on Fatigue, Motor Function and Cognition: A Meta-Analysis of Randomized Controlled Trials
Astaxanthin Alleviates the Process of Cardiac Hypertrophy by Targeting the METTL3/Circ_0078450/MiR-338-3p/GATA4 Pathway Full Text
PEGylated-liposomal astaxanthin ameliorates Aβ neurotoxicity and Alzheimer-related phenotypes by scavenging formaldehyde 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.
*Curcumin effects on glycaemic indices, lipid profile, blood pressure, inflammatory markers and anthropometric measurements of non-alcoholic fatty liver disease patients: A systematic review and meta-analysis of randomized clinical trials Full Text
*Curcumin supplementation effect on liver enzymes in patients with nonalcoholic fatty liver disease: a GRADE-assessed systematic review and dose–response meta-analysis of randomized controlled trials
*Nanocurcumin supplementation improves pulmonary function in severe COPD patients: A randomized, double blind, and placebo-controlled clinical trial

Fisetin
Fisetin suppresses chondrocyte senescence and attenuates osteoarthritis progression by targeting sirtuin 6

Melatonin
Mitochondrial Melatonin: Beneficial Effects in Protecting against Heart Failure Full Text
The potential influence of melatonin on mitochondrial quality control: a review Full Text
Comprehensive review of melatonin as a promising nutritional and nutraceutical supplement Full Text

Nicotinamide MonoNucleotide (NMN)
*Safety and efficacy of long-term nicotinamide mononucleotide supplementation on metabolism, sleep, and nicotinamide adenine dinucleotide biosynthesis in healthy, middle-aged Japanese men Full Text
NAD+ supplementation prevents STING-induced senescence in CD8+ T cells by improving mitochondrial homeostasis
NAD+ dependent UPRmt activation underlies intestinal aging caused by mitochondrial DNA mutations Full Text

Nicotinamide Riboside (NR)
NAD+ Precursors Reverse Experimental Diabetic Neuropathy in Mice Full Text

Pterostilbene
Pterostilbene in the treatment of inflammatory and oncological diseases Full Text

Resveratrol
Resveratrol attenuates advanced glycation end product-induced senescence and inflammation in human gingival fibroblasts Full Text
Unveiling the potential effects of resveratrol in lung cancer treatment: Mechanisms and nanoparticle-based drug delivery strategies Full Text

Other available supplements & natural substances (in alphabetical order)
α-Ketoglutarate improves cardiac insufficiency through NAD+-SIRT1 signaling-mediated mitophagy and ferroptosis in pressure overload-induced mice Full Text
Relationship of Low Vitamin B6 Status with Sarcopenia, Frailty, and Mortality: A Narrative Review Full Text
*Effect of the ketone beta-hydroxybutyrate on markers of inflammation and immune function in adults with type 2 diabetes
*Vitamin D3 inhibits p38 MAPK and senescence-associated inflammatory mediator secretion by senescent fibroblasts that impacts immune responses during ageing Full Text
*The associations of serum vitamin D status and vitamin D supplements use with all-cause dementia, Alzheimer’s disease, and vascular dementia: a UK Biobank based prospective cohort study Full Text
Therapeutic applications of ginseng for skeletal muscle-related disorder management Full Text
Red Ginseng Attenuates the Hepatic Cellular Senescence in Aged Mice Full Text
Hydrogen Water: Extra Healthy or a Hoax?—A Systematic Review Full Text
Exploring the Neuroprotective Effects of Lithium in Ischemic Stroke: A literature review Full Text
*Effect of Nigella sativa Consumption on Lipid Profile and Glycemic Index in Patients with Metabolic Syndrome: A Systematic Review and Meta-analysis of Randomized Controlled Trials
*Cuban policosanol improves high-density lipoprotein cholesterol efflux capacity in healthy Japanese subjects Full Text
Mitophagy curtails cytosolic mtDNA-dependent activation of cGAS/STING inflammation during aging Full Text urolithin A

Combinations of Supplements
*Third major study finds evidence that daily multivitamin supplements improve memory and slow cognitive aging in older adults Abstract
Combination of phytochemicals, including ginsenoside and curcumin, shows a synergistic effect on the recovery of radiation-induced toxicity Full Text
*Combined Turmeric, Vitamin C, and Vitamin D Ready-to-Drink Supplements Reduce Upper Respiratory Illness Symptoms and Gastrointestinal Discomfort in Elite Male Football Players Full Text

Prescription Supplements

Metformin
*Incident dementia risk among patients with type 2 diabetes receiving metformin versus alternative oral glucose-lowering therapy: an observational cohort study using UK primary healthcare records Full Text
*Association of metformin use and cancer incidence: a systematic review and meta-analysis
*Effect of metformin and lifestyle intervention on adipokines and hormones in breast cancer survivors: a pooled analysis from two randomized controlled trials Full Text

Rapamycin (sirolimus)
Rapamycin mitigates inflammation-mediated disc matrix homeostatic imbalance by inhibiting mTORC1 and inducing autophagy through Akt activation Full Text
Rapamycin Alleviates Neuronal Injury and Modulates Microglial Activation After Cerebral Ischemia
Mitophagy Activation by Rapamycin Enhances Mitochondrial Function and Cognition in 5×FAD Mice Full Text

Miscellaneous Molecules & Prescription Drugs
*Cholinesterase inhibitors are associated with reduced mortality in patients with Alzheimer's disease and previous myocardial infarction Full Text
*Effects of SGLT2 Inhibition via Empagliflozin on Cognitive and Physical Impairment in Frail Diabetic Elders with Chronic Kidney Disease Full Text
*(SGLT2) in frail or older people with type 2 diabetes and heart failure: a systematic review and meta-analysis Full Text

Other Areas of Interest (in alphabetical order)

Ageing Clocks & other biomarkers of ageing
*Prognostic accuracy of 70 individual frailty biomarkers in predicting mortality in the Canadian Longitudinal Study on Aging Full Text CAN
Epigenetic drift underlies epigenetic clock signals, but displays distinct responses to lifespan interventions, development, and cellular dedifferentiation Full Text
*Body size, diet quality, and epigenetic ageing: cross-sectional and longitudinal analyses Full Text

Epigenetics & Cellular Reprogramming
Epigenetic Reprogramming as a Key to Reverse Ageing and Increase Longevity Full Text
Epigenetic Reprogramming to Repair Genetic Damage Full Text

Exosomes (small packets of information released by cells)
Exosomes in skin photoaging: biological functions and therapeutic opportunity Full Text
*Acute exercise-induced release of innate immune proteins via small extracellular vesicles changes with aerobic fitness and age Full Text

Genetics including CRISPR
*Alzheimer’s Disease and Aging Association: Identification and Validation of Related Genes
*Investigation of genetic determinants of cognitive change in later life Full Text
Longevity-CancerDB: unlocking the distinctive features and roles of longevity-associated genes in tumourigenesis Full Text

Lifespan Lengthening Interventions
Improved Brain-Fat Communication Extends Lifespan in Mice Full Text
GV1001 reduces neurodegeneration and prolongs lifespan in 3xTg-AD mouse model through anti-aging effects Full Text
Longevity interventions modulate mechanotransduction and extracellular matrix homeostasis in C. elegans Full Text
PICLS with human cells is the first high throughput screening method for identifying novel compounds that extend lifespan Full Text

Microbiome
A gut aging clock using microbiome multi-view profiles is associated with health and frail risk Full Text
Potential of dietary polyphenols for protection from age-related decline and neurodegeneration: a role for gut microbiota? Full Text
Identification of Muscle Strength-Related Gut Microbes through Human Fecal Microbiome Transplantation Full Text

Observational Studies
*Impact of sleep duration and sleep disturbances on the incidence of dementia and Alzheimer's disease: A 10-year follow-up study Full Text
*The Influence of Metabolic Syndrome on Potential Aging Biomarkers in Participants with Metabolic Syndrome Compared to Healthy Controls Full Text
*Implications of metabolism on multi-systems healthy aging across the lifespan Full Text

Opinion/Editorials/Theory
Should the European Medicines Agency consider ageing a disease? Full Text
Growing old while staying young: The unique mechanisms that defy aging in plants Full Text
Seven knowledge gaps in modern biogerontology Full Text
The Gompertz Law emerges naturally from the inter-dependencies between sub-components in complex organisms Full Text
The hallmarks of aging as a conceptual framework for health and longevity research Full Text

Other Ageing Biology
The unfolded protein response of the endoplasmic reticulum protects Caenorhabditis elegans against DNA damage caused by stalled replication forks Full Text CAN
Fibroblast growth factor 21 alleviates diabetes-induced cognitive decline Full Text
Intermittent cytomegalovirus infection alters neurobiological metabolism and induces cognitive deficits in mice Full Text

Regenerative Medicine
Hydrogel-Based Strategies for Intervertebral Disc Regeneration: Advances, Challenges and Clinical Prospects Full Text
Dual delivery gene-activated scaffold directs fibroblast activity and keratinocyte epithelization Full Text

Reproductive Health
The influence of the gut microbiome on ovarian aging Full Text
Human Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes Rescue Testicular Aging Full Text
*Muscle Strength and Male Sexual Function Full Text
Cellular and molecular mechanisms of highly active mesenchymal stem cells in the treatment of senescence of rhesus monkey ovary Full Text
Chitosan Treatment Reduces Ovarian Senescence in Mice Full Text

Reviews
Anti-Aging Drugs and the Related Signal Pathways Full Text
Antiaging Strategies and Remedies: A Landscape of Research Progress and Promise Full Text
Eternal Youth: A Comprehensive Exploration of Gene, Cellular, and Pharmacological Anti-Aging Strategies Full Text

Senolytics/Senescent Cells
Researching New Drug Combinations with Senolytic Activity Using Senescent Human Lung Fibroblasts MRC-5 Cell Line Full Text
Senolytic treatment alleviates doxorubicin-induced chemobrain Full Text

Skin & Beauty
*A proof of concept: Clinical anti-aging efficacy and safety of Lactiplantibacillus plantarum LB244R® applied topically in a double-blinded placebo-controlled study Full Text
*Skin rejuvenation and photoaging protection using adipose-derived stem cell extracellular vesicles loaded with exogenous cargos Full Text
*Beverage consumption and facial skin aging: Evidence from Mendelian randomization analysis Full Text

Telomeres
*Effects of Physical Exercise on Telomere Length in Healthy Adults: Systematic Review, Meta-Analysis, and Meta-Regression Full Text
*The Relationship between Dietary Macronutrient Composition and Telomere Length Among US Adults Full Text

Odds & Sods
Fighting with Aging: The Secret for Keeping Health and Longevity of Naked Mole Rats Full Text
*How aging shapes our sense of agency Full Text
*Social network type contributes to purpose in life among older people, mediated by social support 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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