2021’s Longevity End of Year Review

Introduction

Sitting down to write 2021’s End of Year Review, I had a look at the previous four I’ve done and saw that each followed a different format! Not wishing to break tradition, I’ve once again taken a different tack. Instead of breathlessly selecting the top advances in mouse healthspan, this time I’ve only included human studies (sorry mouse owners, but the end goal is not to create immortal mice!).

Once you scroll past the commentary, you’ll find the top three human studies for each category. If there were no human studies, then that category will not be represented. Likewise, a few supplements/treatments get their own category for the first time as there were human studies.

Hopefully you will find it useful if you are looking for practical steps you can do now to enhance your healthy longevity. And, as some of you might want to see all the relevant human studies for your favourite supplement, I’ve included them in the attachment for your perusal. EDIT: I can't seem to attach PDFs anymore, you can find the PDF here: https://www.patreon....gevity-61648945

I’d be interested in hearing what you thought were the most important human studies from last year.

Some thoughts on 2021

There was nothing scientific about the biggest longevity news of the year - that significant amounts of money have finally begun to flow into the field. From the PulseChain crypto airdrop, which netted the SENS Research Foundation over $20M, to the Longevity Science Foundation committing $1 billion over the next ten years, hardly a week went by without the announcement of a new initiative. There were too many to detail here, but a couple worth highlighting are VitaDao, a community organised funding mechanism, and Impetus Grants, which very quickly gave out small grants to more speculative research projects that might not have gotten funding otherwise. Longevity companies also saw an influx, with over $2 billion raised - a good overview can be found at: Longevity investment 2021: from Seed to SPAC

For too long longevity research has been woefully underfunded, so this is a major step in the right direction and will speed up progress. However, it is still a drop in the ocean to where funding should be considering the beneficial impact it would have.

The other big news was progress towards human trials, in particular February’s announcement by the National Institute of Aging in the USA that they were soliciting proposals for human trials to target ageing related mechanisms, in other words, the ageing process itself. This is the first time that I have seen a government agency fund trials to directly tackle ageing, and although they only have $4.5M allocated, it is still a giant leap forward.

Other trials include a growing number involving senolytics, with Unity presenting some promising results; the ongoing TRIIM-X follow-on trial to 2019’s intriguing TRIIM trial, which tentatively showed epigenetic age reduction in nine men; and, although the TAME trial still appears to be in never ending purgatory, a trial to test rapamycin in Alzheimer’s got off the ground. Finally, the crowdfunded rapamycin PEARL trial exceeded its funding target and is now enrolling participants.

A few research highlights

The underappreciated paper of the year was undoubtedly the discovery of an early embryonic rejuvenation event in mammals, which if confirmed, shows that a form of rejuvenation has happened to each and every one of us already - we just need to recapture that ability.
Embryos appear to reverse their biological clock early in development Full Text jun

And, another overlooked paper was from researchers at the University of Waterloo, who mathematically looked at the best time of day to take supplements (NMN & Resveratrol) based on the circadian rhythm.
Time of day boosts effectiveness of anti-aging supplements Full Text mar

The discovery of the CRISPR-Cas9 gene editing method was one of the biggest breakthroughs of the last decade, so it was great to see that 2021 marked the first human results.
*Landmark CRISPR trial shows promise against deadly disease Abstract jun

Finally, out of all the supplement results you’ll find below, the most interesting and actionable was that a combination of glycine and N-acetylcysteine [NAC] resulted in reduced oxidative stress and improved inflammation, muscle strength and cognition. (With the usual caveat that it was a small study and needs to be replicated)
*GlyNAC improves multiple defects in aging to boost strength and cognition in older humans Full Text mar

Personal Year

Of course, it has been a great year for me with the incorporation of the Canadian Longevity Association in November. It was a long road from initial inception, through getting a web domain and website, to final incorporation. I must once again thank Dmitry Kaminskiy and his team at Deep Knowledge Group for their assistance in getting this over the finish line - without their help, it wouldn’t have happened as quickly.

If you would like to help grow the Canadian Longevity Association and increase its impact through your time, expertise or money, then please get in touch!

Elsewhere, I managed to host a few meetups before covid shut things down again and expanded my volunteer work for Lifespan.io. Where, apart from continuing to provide news and help with their monthly Rejuvenation Roundup, I wrote the text for the Rapamycin human trial (PEARL) crowdfunding campaign and in the summer took over the updating of their Rejuvenation Roadmap. Lastly, I even managed to get some monthly donations on my Patreon page for writing these newsletters!

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***Disclaimer: 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.***
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Covid 19
*Covid-19 patients recover faster with metabolic activator treatment, study shows Full Text jun
*Oral nano-curcumin formulation efficacy in the management of mild to moderate outpatient COVID-19: A randomized triple-blind placebo-controlled clinical trial Full Text aug
*Eating a plant rich diet reduces risk of developing COVID-19 Full Text sep
*Randomized Double-blind Placebo-controlled Proof-of-concept Trial of Resveratrol for Outpatient Treatment of Mild Coronavirus Disease (COVID-19) Full Text sep
*The Effect of Melatonin on Thrombosis, Sepsis and Mortality Rate in COVID-19 Patients Full Text oct

Lifestyle

Fasting/Dietary Restriction
*Time-restricted eating and concurrent exercise training reduces fat mass and increases lean mass in overweight and obese adults Full Text may
*5-Day Fast Improves Longevity Biomarkers in Humans Full Text aug
*Intermittent Fasting and Obesity-Related Health Outcomes Full Text dec

Diet
*Impact of Polyphenolic-Food on Longevity: An Elixir of Life. An Overview Full Text
mar
*Restriction of Dietary Advanced Glycation end Products Induces a Differential Plasma Metabolome and Lipidome Profile Full Text oct
*Crosstalk among intestinal barrier, gut microbiota and serum metabolome after a polyphenol-rich diet in older subjects with “leaky gut”: The MaPLE trial Full Text nov

Exercise
*Effects of a 6 Week Low-Dose Combined Resistance and Endurance Training on T Cells and Systemic Inflammation in the Elderly Full Text apr
*Effects of exercise on cellular and tissue aging Full Text may
*Exercise Decreases Circulating Senescence Proteins Full Text jun
*One-Year Committed Exercise Training Reverses Abnormal Left Ventricular Myocardial Stiffness in Patients With Stage B Heart Failure With Preserved Ejection Fraction Full Text sep

Non-prescription Supplements (in alphabetical order)

Alpha-Ketoglutarate
*Alpha-Ketoglutarate Decreases Biological Age in Human Study Full Text nov
*The study of skin hydration, anti-wrinkles function improvement of anti-aging cream with alpha-ketoglutarate Full Text nov

Astaxanthin
*The antioxidant and anti-inflammatory effects of astaxanthin supplementation on the expression of miR-146a and miR-126 in patients with type 2 diabetes mellitus: A randomized, double-blind, placebo-controlled clinical trial jan
*Astaxanthin supplementation enhances metabolic adaptation with aerobic training in the elderly Full Text jun
*Astaxanthin Supplementation Increases Glutathione Concentrations but Does Not Impact Fat Oxidation During Exercise in Active Young Men oct

Creatine
*Creatine Supplementation and Brain Health Full Text feb
*Meta-Analysis Examining the Importance of Creatine Ingestion Strategies on Lean Tissue Mass and Strength in Older Adults Full Text jun
*Timing of Creatine Supplementation around Exercise: A Real Concern? Full Text aug

Curcumin
*The efficacy of high- and low-dose curcumin in knee osteoarthritis: A systematic review and meta-analysis Full Text sep
*Increasing Post-Digestive Solubility of Curcumin is the most Successful Strategy to Improve its Oral Bioavailability: A Randomized Cross-Over Trial in Healthy Adults and In Vitro Bioaccessibility Experiments Full Text oct
*Effects of Curcumin Supplementation on Inflammatory Markers, Muscle Damage, and Sports Performance during Acute Physical Exercise in Sedentary Individuals Full Text oct

Fisetin
*Fisetin for COVID-19 in Skilled Nursing Facilities (COVID-FIS): Senolytic Trials in the COVID Era Full Text aug
Fisetin, potential flavonoid with multifarious targets for treating neurological disorders: An updated review Full Text sep

Melatonin
*Melatonin and Cardioprotection in Humans: A Systematic Review and Meta-Analysis of Randomized Controlled Trials Full Text may
*Effects of daily administration of melatonin before bedtime on fasting insulin, glucose and insulin sensitivity in healthy adults and patients with metabolic diseases. A systematic review and meta-analysis Full Text aug
*Exercise-induced oxidative stress and melatonin supplementation: current evidence Full Text sep

Nicotinamide MonoNucleotide (NMN)
*NMN Human Trial Suggests Improved Muscle Glucose Metabolism Abstract
*Nicotinamide mononucleotide: a potential effective natural compound against insulin resistance Full Text aug
*NMN Enhances Aerobic Capacity in Amateur Runners Full Text jul

Nicotinamide Riboside (NR)
*Nicotinamide riboside supplementation does not alter whole-body or skeletal muscle metabolic responses to a single bout of endurance exercise jan
*NAD +-boosting therapy alleviates nonalcoholic fatty liver disease via stimulating a novel exerkine Fndc5/irisin Full Text feb
*Nicotinamide Riboside Improves Ataxia Scores and Immunoglobulin Levels in Ataxia Telangiectasia Full Text sep

Resveratrol
*Neuroprotective Effect of Trans-Resveratrol in Mild to Moderate Alzheimer Disease: A Randomized, Double-Blind Trial Full Text aug
*Protective and Recovery Effects of Resveratrol Supplementation on Exercise Performance and Muscle Damage following Acute Plyometric Exercise Full Text sep
*Effect of Resveratrol on Serum Levels of Type II Collagen and Aggrecan in Patients with Knee Osteoarthritis: A Pilot Clinical Study Full Text nov

Spermidine
*Spermidine for Cognitive Function in Flies, Mice, and Humans Full Text apr
*New Insights into the Roles and Mechanisms of Spermidine in Aging and Age-Related Diseases Full Text dec

Urolithin A
*Impact of the Natural Compound Urolithin A on Health, Disease, and Aging Full Text may
*Direct supplementation with Urolithin A overcomes limitations of dietary exposure and gut microbiome variability in healthy adults to achieve consistent levels across the population Full Text jun

Other available supplements
*Effects of n-3 EPA and DHA supplementation on fat free mass and physical performance in elderly. A systematic review and meta-analysis of randomized clinical trial Full Text mar
*Effect of Dietary Pyrroloquinoline Quinone Disodium Salt on Cognitive Function in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study aug
*The effects of 6-month hydrogen-rich water intake on molecular and phenotypic biomarkers of aging in older adults aged 70 years and over: A randomized controlled pilot trial sep
*The Effects of Korean Red Ginseng on Biological Aging and Antioxidant Capacity in Postmenopausal Women: A Double-Blind Randomized Controlled Study Full Text sep

Combinations of Supplements
*Effectiveness of Tinnitan Duo® in Subjective Tinnitus with Emotional Affectation: A Prospective, Interventional Study Full Text jul
*Four-in-one blood pressure pill: Safe and much more effective than usual hypertension treatment, study finds Abstract aug

Prescription Supplements

Metformin
*Metformin and health outcomes: An umbrella review of systematic reviews with meta-analyses Full Text mar
*A Metabolic Pattern in Healthy Subjects Given a Single Dose of Metformin: A Metabolomics Approach Full Text jul
*Effects of Metformin in Heart Failure: From Pathophysiological Rationale to Clinical Evidence Full Text dec

Rapamycin
*Intravitreal sirolimus for persistent, exudative age-related macular degeneration: a Pilot Study Full Text feb
*Rapamycin is Effective for Upper but not for Lower Gastrointestinal Crohn's Disease-Related Stricture: A Pilot Study Full Text feb
*Human Trials of mTOR Inhibitors for Immune Aging Full Text may

Miscellaneous Molecules
*Long Term Effects of Cholinesterase Inhibitors on Cognitive Decline and Mortality Full Text mar
*Knee Osteoarthritis Pain Management with an Innovative High and Low Molecular Weight Hyaluronic Acid Formulation (HA-HL): A Randomized Clinical Trial Full Text aug

Other Areas of Interest (in alphabetical order)

Ageing Clocks & other biomarkers of ageing
*Epigenetic age is associated with baseline and 3-year change in frailty in the Canadian Longitudinal Study on Aging Full Text aug
*Epigenetic age prediction Full Text aug
*The association between epigenetic clocks and physical functioning in older women: a three-year follow-up Full Text sep

Blood Factors or other Heterochronic Transplantation
*Safety and Tolerability of GRF6019 Infusions in Severe Alzheimer's Disease: A Phase II Double-Blind Placebo-Controlled Trial may
*Neuropsychological, neuropsychiatric, and quality-of-life assessments in Alzheimer's disease patients treated with plasma exchange with albumin replacement from the randomized AMBAR study Full Text nov
*Efficacy of Cord Blood Cell Therapy for Hutchinson–Gilford Progeria Syndrome—A Case Report Full Text nov

Epigenetics & Cellular Reprogramming
*Diet, Exercise Reduce Epigenetic Age in Human Clinical Trial Full Text apr
*A systematic review of biological, social and environmental factors associated with epigenetic clock acceleration Full Text apr
*Activity and Diet Shown to Slow Aging (Again) Full Text sep

Genetics including CRISPR
*Protein signatures of centenarians and their offspring suggest centenarians age slower than other humans Full Text jan
*The risk of developing a disease linked to genetics tends to decrease with age Full Text aug
*Multi-omics Identifies Longevity Genes, Therapeutic Targets Full Text oct

Hyperbaric Oxygen Therapy
*Hyperbaric oxygen therapy alleviates vascular dysfunction and amyloid burden in an Alzheimer’s disease mouse model and in elderly patients Full Text sep
*A Clinical Trial of Hyperbaric Oxygen Therapy for Skin Aging Full Text nov
*Hyperbaric oxygen therapy induces transcriptome changes in elderly: a prospective trial Full Text nov

Lifespan Lengthening Interventions (mice only!)
Cap-independent translation: A shared mechanism for lifespan extension by rapamycin, acarbose, and 17α-estradiol Full Text mar
17-a-estradiol late in life extends lifespan in aging UM-HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex Full Text mar
Lithium can mildly increase health during ageing but not lifespan in mice Full Text sep
Dietary citrate supplementation enhances longevity, metabolic health, and memory performance through promoting ketogenesis Full Text oct
Daily ingestion of Akkermansia mucciniphila for one month promotes healthy aging and increases lifespan in old female mice nov

Microbiome
*The Effect of Probiotics on Health Outcomes in the Elderly: A Systematic Review of Randomized, Placebo-Controlled Studies Full Text jun
*Lactobacillus plantarum TWK10 Improves Muscle Mass and Functional Performance in Frail Older Adults: A Randomized, Double-Blind Clinical Trial Full Text jul
*Synbiotic Supplementation Improves Obesity Index and Metabolic Biomarkers in Thai Obese Adults: A Randomized Clinical Trial Full Text jul

Observational Studies
*Associations Between Sleep Quality and Health Span: A Prospective Cohort Study Based on 328,850 UK Biobank Participants Full Text jun
*Increasingly capable at the ripe old age? Cognitive abilities from 2004 to 2013 in Germany, Spain, and Sweden Full Text jul
*The Link Between Brain Age and Blood Pressure Full Text oct

Opinion/Editorials/Theory
*Demographic perspectives on the rise of longevity Full Text mar
*50 years of the “war on cancer”: lessons for public health and geroscience Full Text apr
*The longevity society Full Text dec

Reviews
Cellular reprogramming and epigenetic rejuvenation Full Text sep
Friends and foes: Extracellular vesicles in aging and rejuvenation Full Text jul
Strategies for targeting senescent cells in human disease Full Text oct

Senolytics/Senescent Cells
*Senolytics Show Positive Results in Phase 1 Clinical Trial Press Release jul
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