February 2022 Longevity Review

Welcome to another month of progress in the field of longevity. Although the geopolitical news has turned bleak, hopefully some solace, or at least some distraction can be found in science.

This month you'll find a couple of actionable studies relating to diet and exercise in the Round-Up, as well as a good overview of the clinical trials targeting ageing done to date. There are also some more trial results for certain supplements peppered throughout, in addition to the usual wealth of other interesting studies.

This month also marks the start of a small revamp of this newsletter, transitioning from being personal to representing the Canadian Longevity Association. The majority of the newsletter will remain unchanged, however I am introducing a Canadian Spotlight section, which, as the name suggests, will highlight a Canadian company, institution or organisation connected to longevity. Also, instead of just mentioning what I have been up to, it will mention what the CLA has been doing since we now have some industrious volunteers.

CLA News

Apart from a couple of very useful meetings with Anne Marie and David Wright from YouAreUNLTD and Todd White from VitaDao, most of the time was spent doing organisational infrastructure work, the details of which I won’t bore you with. The biggest advance was that we decided what direction to take for the new website in terms of platform etc and did some preparatory work, in addition to moving the existing site to Cloudflare and making it secure.

We are always looking for more help or volunteers, regardless of your skill set or time availability. If you’d be interested in helping us, please fill out this Volunteer Registration Form.

The CLA now has its own Twitter account, so you can follow us @canlongevity in addition to my personal account @ChrisPollyanna1

For previous newsletters, you can find them in the Canadian Longevity Association Facebook group, and also my Patreon account, which includes bonus material for supporters.

Canadian Longevity Spotlight

AgeRate

A Hamilton based start-up which aims to provide consumers with epigenetic age testing combined with a mobile app to give health recommendations. AgeRate is in the middle of beta testing and there are still places available if you'd like to find out your biological age at a steeply discounted price - you can sign up here. In addition, AgeRate is also looking for additional funding, so if you are an investor interested in the longevity sector, please contact them here.

February Round-Up:

Starting off with a couple of actionable studies, the first of which lets you calculate how changing your diet might affect your life expectancy. It’s fun to play around with the calculator, which I’ve included below. The second study provides guidance as to how much and what types of exercise you need to do to improve your cognitive function when older.
*Changing your diet could add up to a decade to life expectancy, study finds Full Text
Food4HealthyLife calculator

*Exercise Improves Cognition Depending on Type and Amount Full Text

After initially having to rely on mouse studies, we are finally starting to see more human results about using NMN to boost our NAD+ levels - here is the latest. A few more NMN studies were supposedly completed last year, so we should hopefully see their results soon.
*Effect of 12-Week Intake of Nicotinamide Mononucleotide on Sleep Quality, Fatigue, and Physical Performance in Older Japanese Adults: A Randomized, Double-Blind Placebo-Controlled Study Full Text

In what might be a first for this newsletter, I’m highlighting an electronic device which can produce a degree of rejuvenation. Here, a pacemaker which introduces a variable heart rate, improves cardiac output by 20% in sheep compared to traditional pacemakers.
'Bionic' pacemaker reverses heart failure Full Text

It is always good now and then to take stock of progress in human longevity interventions, which this nice little review does. Hopefully, it will soon be a lot longer!
*Clinical Trials Targeting Aging Full Text

And finally, biology never ceases to throw up surprises: while it has become apparent that the gut microbiome can influence cognition, it also turns out that phages, viruses which infect bacteria, can do likewise. Yet another layer to unravel!
*Gut Viruses Found to Improve Cognition in Humans Full Text

Supplemental Section

Lifestyle
*Determinants of healthy ageing: a systematic review of contemporary literature 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.
*Caloric Restriction Promotes Rejuvenation in Human Trials Abstract
*Time-Restricted Eating: Integrating The What With The When Full Text
*Lean mass sparing in resistance-trained athletes during caloric restriction: the role of resistance training volume Full Text

Diet – let food be thy medicine…
*Systematic review and meta-analysis of protein intake to support muscle mass and function in healthy adults Full Text
*Effect of berry-based supplements and foods on cognitive function: a systematic review Full Text

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*Resistance exercise as a treatment for sarcopenia: prescription and delivery Full Text
*Study shows exercise can help older adults retain their memories 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.

Curcumin – the spice which gives curries their yellow colour. Anti-inflammatory and neuroprotective. Needs to be taken with black pepper (piperine) to improve bioavailability.
*Effects of curcumin supplementation on metabolic parameters, inflammatory factors and obesity values in women with rheumatoid arthritis: A randomized, double-blind, placebo-controlled clinical trial
*Does nano-curcumin supplementation improve hematological indices in critically ill patients with sepsis? A randomized controlled clinical trial
*Therapeutic Applications of Curcumin in Diabetes: A Review and Perspective Full Text

Fisetin
Fisetin attenuates renal ischemia/reperfusion injury by improving mitochondrial quality, reducing apoptosis and oxidative stress

Melatonin – a natural hormone produced in the pineal gland, it helps us to fall asleep every night, but it has many other functions, including as a mitochondrial antioxidant.
*Melatonin supplementation improves N-terminal pro-B-type natriuretic peptide levels and quality of life in patients with heart failure with reduced ejection fraction: Results from MeHR trial, a randomized clinical trial Full Text
Melatonin enhances osteoblastogenesis of senescent bone marrow stromal cells through NSD2-mediated chromatin remodelling Full Text
Role of melatonin in respiratory diseases Full Text

Nicotinamide MonoNucleotide (NMN)
*MIB-626, an Oral Formulation of a Microcrystalline Unique Polymorph of β-Nicotinamide Mononucleotide, Increases Circulating Nicotinamide Adenine Dinucleotide and its Metabolome in Middle-aged and Older Adults
Multispectral autofluorescence characteristics of reproductive aging in old and young mouse oocytes Full Text

Nicotinamide Riboside (NR)
Intravenous nicotinamide riboside elevates mouse skeletal muscle NAD+ without impacting respiratory capacity or insulin sensitivity Full Text

Pterostilbene
Oral Delivery of Pterostilbene by L-Arginine-Mediated “Nano-Bomb” Carrier for the Treatment of Ulcerative Colitis Full Text
Pterostilbene Promotes Mean Lifespan in Both Male and Female Drosophila Melanogaster Modulating Different Proteins in the Two Sexes Full Text

Resveratrol
*Effects of Resveratrol Supplementation on the Cognitive Function of Patients with Alzheimer's Disease: A Systematic Review of Randomized Controlled Trials
*Resveratrol and Reproductive Health Full Text
Resveratrol Ameliorates Erectile Dysfunction in Old Rats Full Text

Other available supplements (in alphabetical order)
Apigenin Alleviates Intervertebral Disc Degeneration via Restoring Autophagy Flux in Nucleus Pulposus Cells Full Text
Effects of Creatine Supplementation on Brain Function and Health Full Text
The Panax ginseng Berry Extract and Soluble Whey Protein Hydrolysate Mixture Ameliorates Sarcopenia-Related Muscular Deterioration in Aged Mice Full Text
The neuroprotective effects of icariin on ageing, various neurological, neuropsychiatric disorders, and brain injury induced by radiation exposure Full Text
Age-related GSK3β overexpression drives podocyte senescence and glomerular aging Full Text Lithium
Lycopene Improves Bone Quality and Regulates AGE/RAGE/NF-кB Signaling Pathway in High-Fat Diet-Induced Obese Mice Full Text

Combinations of Supplements
The combination of nicotinamide mononucleotide and lycopene prevents cognitive impairment and attenuates oxidative damage in D-galactose induced aging models via Keap1-Nrf2 signaling
Mitoprotective Effects of a Synergistic Nutraceutical Combination: Basis for a Prevention Strategy Against Alzheimer’s Disease Full Text
*The Effects of Lutein and Zeaxanthin Supplementation on Cognitive Function in Adults With Self-Reported Mild Cognitive Complaints: A Randomized, Double-Blind, Placebo-Controlled Study Full Text
A Synergistic Combination of DHA, Luteolin, and Urolithin A Against Alzheimer’s Disease Full Text
Rebalance of the Polyamine Metabolism Suppresses Oxidative Stress and Delays Senescence in Nucleus Pulposus Cells Full Text Spermidine & NAC

Prescription Supplements

Metformin
*Metformin: Expanding the Scope of Application—Starting Earlier than Yesterday, Canceling Later Full Text
*Patients with Obesity and a History of Metformin Treatment Have Lower Influenza Mortality: A Retrospective Cohort Study Full Text
*Metformin and the heart: Update on mechanisms of cardiovascular protection with special reference to comorbid type 2 diabetes and heart failure Full Text

Rapamycin (sirolimus)
Rapamycin Improved Retinal Function and Morphology in a Mouse Model of Retinal Degeneration Full Text
Rapamycin attenuated podocyte apoptosis via upregulation of nestin in Ang II-induced podocyte injury Full Text
mTOR inhibition prevents angiotensin II–induced aortic rupture and pseudoaneurysm but promotes dissection in Apoe-deficient mice Full Text

Miscellaneous Molecules
Pharmacological Depletion of Microglia Leads to a Dose-Dependent Reduction in Inflammation and Senescence in the Aged Murine Brain Full Text
Diabetes, metabolic syndrome in mice treated with novel class of compounds Full Text
Rescuing the negative effects of aging in burn wounds using tacrolimus applied via microcapillary hydrogel dressing Full Text

Other Areas of Interest (in alphabetical order)

Ageing Clocks & other biomarkers of ageing
*Combining Epigenetic and Imaging Biomarkers Full Text
*Work-related stress and well-being in association with epigenetic age acceleration: A Northern Finland Birth Cohort 1966 Study Full Text
Tick tock, tick tock: Mouse culture and tissue aging captured by an epigenetic clock Full Text

Blood Factors or other Heterochronic Transplantation
Old blood from heterochronic parabionts accelerates vascular aging in young mice: transcriptomic signature of pathologic smooth muscle remodeling

Epigenetics & Cellular Reprogramming
The relationship between ageing and changes in the human blood and brain methylomes Full Text
*Epigenome-wide association study of incident type 2 diabetes: a meta-analysis of five prospective European cohorts Full Text
*Ribosomal DNA methylation in human and mouse oocytes increases with age Full Text

Exosomes (small packets of information released by cells)
Educating EVs to Improve Bone Regeneration: Getting Closer to the Clinic Full Text
Small Extracellular Vesicles from Peripheral Blood of Aged Mice Pass the Blood-Brain Barrier and Induce Glial Cell Activation Full Text

Genetics including CRISPR
Activation of melatonin receptor 1 by CRISPR-Cas9 activator ameliorates cognitive deficits in an Alzheimer's disease mouse model
The Mitochondrial Genome in Aging and Disease and the Future of Mitochondrial Therapeutics Full Text
*Identification of Genetic Networks Reveals Complex Associations and Risk Trajectory Linking Mild Cognitive Impairment to Alzheimer’s Disease Full Text

Lifespan Lengthening Interventions
Lifespan extension with preservation of hippocampal function in aged system xc−-deficient male mice Full Text
Jobelyn® extends the life span and improves motor function in Drosophila melanogaster exposed to lipopolysaccharide via augmentation of antioxidant status
Honeysuckle extract (Lonicera pallasii L.) exerts antioxidant properties and extends the lifespan and healthspan of Drosophila melanogaster

Microbiome
*Efficacy and Safety of Probiotics for the Treatment of Alzheimer's Disease, Mild Cognitive Impairment, and Parkinson's Disease: A Systematic Review and Meta-Analysis Full Text
Mycobacterium vaccae immunization in rats ameliorates features of age-associated microglia activation in the amygdala and hippocampus Full Text
*Association of the Gut Microbiota With Cognitive Function in Midlife Full Text

Observational Studies
*Differences in Cognitive Functioning in Two Birth Cohorts Born 20 Years Apart: Data from the Interdisciplinary Longitudinal Study of Ageing Full Text
*Improved cardiovascular profile in Danish centenarians? A comparative study of two birth cohorts born 20 years apart
*Human brain doesn't slow down until after 60 Abstract

Opinion/Editorials/Theory
The selection force weakens with age because ageing evolves and not vice versa Full Text
Telomeres, aging, and cancer: the big picture Full Text
Universal relation for life-span energy consumption in living organisms: Insights for the origin of aging Full Text
An Evolution-Based Model of Causation for Aging-Related Diseases and Intrinsic Mortality: Explanatory Properties and Implications for Healthy Aging Full Text

Other Ageing Biology
SIRT6 stabilization and cytoplasmic localization in macrophages regulates acute and chronic inflammation in mice Full Text
Targeting IL-36 improves age-related coronary microcirculatory dysfunction and attenuates myocardial ischaemia-reperfusion injury in mice Full Text
Pharmacological Blockade of NLRP3 Inflammasome/IL-1β-Positive Loop Mitigates Endothelial Cell Senescence and Dysfunction Full Text

Regenerative Medicine
Complex three-dimensional kidney tissue generated in the lab from the scratch Full Text
Connecting science to medicine: Tendon-like tissue created from human stem cells Full Text

Reviews
Geroprotectors and Skeletal Health: Beyond the Headlines Full Text
A systems-approach to NAD+ restoration Full Text
*Phenolic Acids and Prevention of Cognitive Decline: Polyphenols with a Neuroprotective Role in Cognitive Disorders and Alzheimer’s Disease Full Text

Senolytics/Senescent Cells
Using Gene Expression to Target Senescent Cells Full Text
Dasatinib plus quercetin attenuates some frailty characteristics in SAMP10 mice Full Text
Synergistic Anti-Ageing through Senescent Cells Specific Reprogramming Full Text

Skin & Beauty
*Collagen Supplements for Aging and Wrinkles: A Paradigm Shift in the Fields of Dermatology and Cosmetics Full Text
*Application of Nonsurgical Modalities in Improving Facial Aging Full Text
*Efficacy of a topical serum containing l-ascorbic acid, neohesperidin, pycnogenol, tocopherol and hyaluronic acid in relation to skin aging signs

Stem Cells
Mesenchymal stem cells combined with autocrosslinked hyaluronic acid improve mouse ovarian function by activating the PI3K-AKT pathway in a paracrine manner Full Text
*Application of stem cells in the repair of intervertebral disc degeneration Full Text
Alzheimer’s Disease: From Pathogenesis to Mesenchymal Stem Cell Therapy – Bridging the Missing Link Full Text*

Telomeres
*Does Exercise Affect Telomere Length? A Systematic Review and Meta-Analysis of Randomized Controlled Trials Full Text
*Leukocyte Telomere Length Correlates with Extended Female Fertility Full Text
*Telomere dysfunction in ageing and age-related diseases Full Text

Odds & Sods
*Cannabis Use and Resting State Functional Connectivity in the Aging Brain Full Text
*Evidence that dog ownership protects against the onset of disability in an older community-dwelling Japanese population Full Text
*Horticultural therapy for general health in the older adults: A systematic review and meta-analysis Full Text
*High-definition transcranial direct current stimulation enhances network segregation during spatial navigation in mild cognitive impairment Full Text
*Effects of Hyperbaric Oxygen Therapy on Mitochondrial Respiration and Physical Performance in Middle-Aged Athletes: A Blinded, Randomized Controlled Trial Full Text
Naked mole-rats maintain cardiac function and body composition well into their fourth decade of life Full Text
Natural disaster and immunological aging in a nonhuman primate

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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 *bolded any human trials.*