Chris’s new November Newsletter: (from the Canadian Longevity Association)
November 2022 Longevity Review
Apart from the first results of my n=1 rapamycin trial, this month you’ll find senolytics for skincare and rapamycin for IVF treatment among the highlights, along with why natural remedies aren’t necessarily better than pharmaceuticals and a rather simple solution to reduce cognitive decline for those with hearing loss.
In the supplemental section there is the suggestion that cellular enlargement is a potential new “Hallmark of Ageing”, as well as how much resistance exercise is needed for longevity and what the best time for exercise is. In addition, clinical NMN trials are coming in thick and fast now, with two more making an appearance this month. Of course, this is just scratching the surface!
Canadian Longevity Association
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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 if you want to buy me a coffee.
CLA News
Finally a little bit of news from the CLA: we had a small dinner to celebrate our one year anniversary of incorporation at the Amsterdam Brewery in Toronto. I only organised it at the last minute, so many people already had other plans, but for those who came, the stimulating discussion stretched late into the night. 
Chris’s n=1 Rapamycin Trial
I’m now one dose away from finishing my three month rapamycin trial, but I’ve already had the first positive and negative results.
Starting with the positive, I had my post-bloodwork done for my annual check up, and apart from one reading (see below) everything was good and within the normal range. When I put the results into the Levine phenotypic age calculator, my pheno age went from 41.1 years to 35.7!! I take this calculator with a fistful of salt, but still, nice to see it move in the right direction. You can see the pre and post calculations here: Pre-Rapamycin Post-Rapamycin
On the negative side, I might be suffering from glucose dysregulation, which is a potential side effect and is the reason I have worn a continuous glucose monitor. I wore one a week before and for the first three weeks of the trial. I then started wearing one again two weeks ago. Comparing the two, I notice that I’m now getting a glucose spike in the mornings without having eaten anything and my blood work gave me an HA1C level of 6.6 which is in the diabetic range! I need to investigate the significance of this more. However, I will have my HA1C tested again in a few months and I will once again wear a CGM post-rapamycin to see if the morning glucose spike goes away.
November 2022 Round-Up:
Back in August, I was sufficiently impressed with a pre-print, showing that partial epigenetic reprogramming via chemical means was possible, to include it in that month’s Round Up. Little did I realise that a similar study had already been published in April! The importance of finding chemical means to reprogram cells lies with its potential for human translation, as the previous genetic methods are not readily feasible for human use.
Chemical journey of somatic cells to pluripotency Abstract Full Text (April 2022)
Although we might hate to admit it, most of us possess some vanity, so there is a large market for skin creams among other things. Now imagine that they actually worked! That is the promise behind using senolytics to rejuvenate the skin as these two studies indicate. There is already a skin care company selling a senolytic skin cream, but I have yet to see any published results from them apart from a toxicity study.
Glutaminase inhibitors rejuvenate human skin via clearance of senescent cells: Mouse/human chimeric model study Full Text
Navitoclax (ABT-263) rejuvenates human skin by eliminating senescent dermal fibroblasts in a mouse/human chimeric model
With people increasingly delaying having children, the need for IVF treatment has grown. Here, a couple of studies from the same group show that rapamycin can enhance this process and elevate the number of high-quality embryos.
Rapamycin Improves the Viability of Egg Cells Full Text
Rapamycin improves developmental competence of human oocytes by alleviating DNA damage during IVM Full Text
Quite often in biohacking/supplement communities there is the temptation to find “natural” remedies in place of drugs from “big bad pharma”. However, the claims for these remedies often exceed the available evidence, as in the case of this study which compared statins to a number of different supplements. If you desire to reduce your cholesterol, it is best to stick to the prescription drug. Caveat emptor!
*Statins vs. supplements: New study finds one is ‘vastly superior’ to cut cholesterol Full Text
And finally, this systematic review provides evidence that there is a simple solution for those with hearing loss to stave off cognitive decline: get a hearing aid!
*Effect of hearing aids on cognitive functions in middle-aged and older adults with hearing loss: A systematic review and meta-analysis Full Text
Supplemental Section
Lifestyle
*Can dementia risk be reduced by following the American Heart Association’s Life’s Simple 7? A systematic review and dose-response meta-analysis 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.
*The Role of Intermittent Fasting in the Management of Nonalcoholic Fatty Liver Disease: A Narrative Review Full Text
The effects of time-restricted eating on sleep, cognitive decline, and Alzheimer’s disease Full Text
Time restricted feeding modifies leukocyte responsiveness and improves inflammation outcome Full Text
Diet – let food be thy medicine…
*Protein Content in an Optimal Diet Full Text
*Processed foods key to rising obesity Full Text
*Polyphenols Help Reduce Visceral Fat Full Text (September 2022)
*Ketogenic diets and Ketone supplementation: A strategy for therapeutic intervention Full Text
Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*How much resistance exercise is beneficial for healthy aging and longevity? Full Text
*Setting your clock: associations between timing of objective physical activity and cardiovascular disease risk in the general population Full Text
*Exercise Might Protect from Metastatic Cancer 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.
A protein- and fiber-rich diet with astaxanthin alleviates high-fat diet-induced obesity in beagles Full Text (Oct 2022)
Multiple roles of fucoxanthin and astaxanthin against Alzheimer’s disease: Their pharmacological potential and therapeutic insights 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: A dietary phytochemical for boosting exercise performance and recovery Full Text
Curcumin-Added Whey Protein Positively Modulates Skeletal Muscle Inflammation and Oxidative Damage after Exhaustive Exercise Full Text
Curcuminoids, a major turmeric component, have a sleep-enhancing effect by targeting the histamine H1 receptor
Fisetin
Fisetin reduces the senescent tubular epithelial cell burden and also inhibits proliferative fibroblasts in murine lupus nephritis Full Text
Melatonin – a natural hormone produced in the pineal gland, it helps us fall asleep every night, but it has many other functions, including as a mitochondrial antioxidant.
Melatonin: A Neurotrophic Factor? Full Text
*Efficacy and safety of oral melatonin in patients with severe COVID-19: a randomized controlled trial Full Text
Melatonin–Microbiome Two-Sided Interaction in Dysbiosis-Associated Conditions Full Text
Nicotinamide MonoNucleotide (NMN)
*Effects of nicotinamide mononucleotide on older patients with diabetes and impaired physical performance: A prospective, placebo-controlled, double-blind study
*Nicotinamide Mononucleotide Is Safely Metabolized and Significantly Reduces Blood Triglyceride Levels in Healthy Individuals Full Text (Sep 2022)
Nicotinamide Riboside (NR)
NAD+ Therapeutics and Skeletal Muscle Adaptation to Exercise in Humans Full Text
The mitochondrial unfolded protein response (UPRmt) protects against osteoarthritis Full Text
Pterostilbene
Comprehensive Analysis of Pterostilbene Metabolites In Vivo and In Vitro Using a UHPLC-Q-Exactive Plus Mass Spectrometer with Multiple Data-Mining Methods Full Text
Pterostilbene attenuates intrauterine growth retardation-induced colon inflammation in piglets by modulating endoplasmic reticulum stress and autophagy Full Text
Resveratrol
Progress in the Preclinical and Clinical Study of Resveratrol for Vascular Metabolic Disease Full Text
Resveratrol attenuates cigarette smoke extract induced cellular senescence in human airway epithelial cells by regulating the miR-34a/SIRT1/NF-κB pathway Full Text
Protective Effect of Resveratrol in an Experimental Model of Salicylate-Induced Tinnitus Full Text
Spermidine
*Association of spermidine plasma levels with brain aging in a population-based study Full Text
Spermidine rejuvenates T lymphocytes and restores anticancer immunosurveillance in aged mice Full Text
Other available supplements (in alphabetical order)
*Daily Low-Dose Aspirin and Risk of Serious Falls and Fractures in Healthy Older People: A Substudy of the ASPREE Randomized Clinical Trial
*Influence of vitamin D supplementation on immune function of healthy aging people: A pilot randomized controlled trial Full Text
*Genistein effect on cognition in prodromal Alzheimer’s disease patients. The GENIAL clinical trial Full Text
Glucosamine delays the progression of osteoporosis in senile mice by promoting osteoblast autophagy Full Text
*Effect of supplementation with leucine alone, with other nutrients or with physical exercise in older people with sarcopenia: a systematic review
*Potentially Beneficial Effects on Healthy Aging by Supplementation of the EPA-Rich Microalgae Phaeodactylum tricornutum or Its Supernatant—A Randomized Controlled Pilot Trial in Elderly Individuals Full Text
Combinations of Supplements
*Small-Scale Randomized Controlled Trial to Explore the Impact of β-Hydroxy-β-Methylbutyrate Plus Vitamin D3 on Skeletal Muscle Health in Middle Aged Women Full Text
*Bioactive Yoghurt Containing Curcumin and Chlorogenic Acid Reduces Inflammation in Postmenopausal Women Full Text
Simultaneous SGLT2 inhibition and caloric restriction improves insulin resistance and kidney function in OLETF rats Full Text
Prescription Supplements
Metformin
*The potential benefit of metformin to reduce delirium risk and mortality: a retrospective cohort study Full Text
*Metformin is associated with reduced COVID-19 severity in patients with prediabetes Full Text
*The Risk of Multiple Myeloma Is Reduced in Metformin Initiators: A Retrospective Cohort Study in Taiwanese Patients with Type 2 Diabetes Mellitus Full Text
Rapamycin (sirolimus)
Rapamycin, not Dietary Restriction, Fights Infection in Mice Full Text
Early or late-life treatment with acarbose or rapamycin improves physical performance and affects cardiac structure in aging mice
Inhibition of mTOR improves malnutrition induced hepatic metabolic dysfunction Full Text
Miscellaneous Molecules & Prescription Drugs
*Antihypertensive medication classes and the risk of dementia over a decade of follow-up Full Text
Long-term atorvastatin improves cognitive decline by regulating gut function in naturally ageing rats Full Text
Glucagon-like Peptide-1 (GLP-1) Receptor Agonists and Neuroinflammation: Implications for Neurodegenerative Disease Treatment Full Text
*SGLT2 inhibitors in heart failure: insights from plasma proteomics Full Text
Other Areas of Interest (in alphabetical order)
Ageing Clocks & other biomarkers of ageing
Unsupervised learning of aging principles from longitudinal data Full Text
*Positive social factors prospectively predict younger epigenetic age: Findings from the Health and Retirement Study
*A urinary proteomic marker indicative of premature ageing Full Text
Epigenetics & Cellular Reprogramming
In vivo partial reprogramming by bacteria promotes adult liver organ growth without fibrosis and tumorigenesis Full Text
Epigenetic regulation of aging: implications for interventions of aging and diseases Full Text
Age reprogramming: cell rejuvenation by partial reprogramming Full Text
Exosomes (small packets of information released by cells)
Extracellular vesicles as personalized medicine Full Text
Preconditioned Mesenchymal Stromal Cell-Derived Extracellular Vesicles (EVs) Counteract Inflammaging Full Text
Extracellular vesicle-derived miRNAs improve stem cell-based therapeutic approaches in muscle wasting conditions Full Text
Genetics including CRISPR
*CRISPR Shows Promise for Hereditary Angioedema in First-in-Human Trial Full Text
CRISPR/Cas9-engineered mesenchymal stromal/stem cells and their extracellular vesicles: A new approach to overcoming cell therapy limitations Full Text
Gene co-expression analyses of health(span) across multiple species Full Text
Lifespan Lengthening Interventions
Lifespan and Healthspan via DAF-16/FOXO and SKN-1/NRF2 Signaling Pathways Full Text
Gender-Specific Effects of Pro-longevity Interventions in Drosophila Full Text
Anti-hsa-miR-59 alleviates premature senescence associated with Hutchinson-Gilford progeria syndrome in mice Full Text
Cytosolic and mitochondrial tRNA synthetase inhibitors increase lifespan in a GCN4/atf-4-dependent manner Full Text
Towards the development of phytoextract based healthy ageing cognitive booster formulation, explored through Caenorhabditis elegans model Full Text
SIRT7 Deficiency Protects against Aging-Associated Glucose Intolerance and Extends Lifespan in Male Mice Full Text
Microbiome
Happy ageing by trusting our gut microbes Full Text
*Take probiotics alongside your prescribed antibiotics to reduce damage to your gut microbiome, says the first review of the data Abstract
*Impact of probiotics on muscle mass, muscle strength and lean mass: a systematic review and meta-analysis of randomized controlled trials Full Text
Observational Studies
*Correlation Between Cognitive Decline and Epigenetic Clocks Full Text
*Twin study links exercise to beneficial epigenetic changes Full Text
*Is life expectancy higher in countries and territories with publicly funded health care? Global analysis of health care access and the social determinants of health Full Text
Opinion/Editorials/Theory
Cellular enlargement - A new hallmark of aging? Full Text
Aging, Equality and the Human Healthspan Full Text
Quantum Healthy Longevity for healthy people, planet, and growth Full Text
Other Ageing Biology
*Measurements of damage and repair of binary health attributes in aging mice and humans reveal that robustness and resilience decrease with age, operate over broad timescales, and are affected differently by interventions Full Text
Finding Interventions That Truly Impact Aging Full Text
Identifying C. elegans lifespan mutants by screening for early-onset protein aggregation Full Text
Reproductive Health
Gene Therapy to Delay Reproductive Senescence Full Text
Cycloastragenol activation of Telomerase improves β-Klotho protein level and attenuates age-related malfunctioning in ovarian tissues Full Text
Epigallocatechin-3-gallate protects porcine oocytes against post-ovulatory aging through inhibition of oxidative stress Full Text
Reviews
Rejuvenation: Turning Back Time by Enhancing CISD2 Full Text
Organotypic cultures as aging associated disease models Full Text
Plasmalogens inhibit neuroinflammation and promote cognitive function Full Text
Senolytics/Senescent Cells
Autologous NK cells propagated and activated ex vivo decrease senescence markers in human PBMCs Full Text
A Glb1-2A-mCherry reporter monitors systemic aging and predicts lifespan in middle-aged mice Full Text
Midazolam alleviates cellular senescence in SH-SY5Y neuronal cells in Alzheimer’s disease Full Text
Skin & Beauty
*Targeting Multiple Hallmarks of Skin Aging: Preclinical and Clinical Efficacy of a Novel Growth Factor-Based Skin Care Serum Full Text
*Adipose Autologous Micrograft and Its Derived Mesenchymal Stem Cells in a Bio Cross-Linked Hyaluronic Acid Scaffold for Correction Deep Wrinkles, Facial Depressions, Scars, Face Dermis and Its Regenerations: A Pilot Study and Cases Report Full Text
*HA PEGylated Filler in Association with an Infrared Energy Device for the Treatment of Facial Skin Aging: 150 Day Follow-Up Data Report Full Text
Stem Cells
*Mesenchymal stromal cell therapy compared to SGLT2-inhibitors and usual care in treating diabetic kidney disease: A cost-effectiveness analysis Full Text
Old mice regain leg strength after antibody treatment Abstract
Aging and Mesenchymal Stem Cells: Basic Concepts, Challenges and Strategies Full Text
Telomeres
Telomeres expand sphere of influence: emerging molecular impact of telomeres in non-telomeric functions Full Text
*Potential effect of dietary zinc intake on telomere length: A cross-sectional study of US adults Full Text
The telomerase connection of the brain and its implications for neurodegenerative diseases Full Text
Odds & Sods
*Decreased lifespan in female “Munchkin” actors from the cast of the 1939 film version of The Wizard of Oz does not support the hypothesis linking hypopituitary dwarfism to longevity
*A Randomized, Controlled Pilot Study of Mindfulness-Based Stress Reduction in Healthy Older Adults Full Text
*Dual-targeted repetitive transcranial magnetic stimulation modulates brain functional network connectivity to improve cognition in mild cognitive impairment patients Full Text
*Centenarians born before 1919 are resistant to COVID-19 Full Text
*Household air cleaners improve heart health among individuals with COPD, researchers find Abstract
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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.
