October 2020 Longevity Review

Posted by Chris Pollyanna , 14 November 2020 · 1,797 views

supplements covid metformin resveratrol reprogramming

Hello and welcome again to this month’s longevity review. As COVID 19 surges once again across the northern hemisphere, I wanted to shine a bit of light on the fact that at heart COVID is yet another disease of ageing, at least in its pathological implications. After all, it is primarily the elderly who suffer complications or morbidity from it as a result of their ageing immune systems and general systemic decline. If one agrees with this, then one would think that interventions which tackle that decline could also prove useful in the prevention and treatment of COVID.

Over the last six months, this is what I have been seeing time and time again during my ageing research, which is why I created the extra subsection on COVID. It has been rather heartening to see that all of the supplements I, and more importantly my parents, take have been proposed to be beneficial in the fight against this dreadful scourge. As a result, I’ve expanded the number of articles devoted to COVID this month.

However, I want to make it abundantly clear that these supplements are not a substitute for mask wearing and social distancing. Please don’t think that taking a couple of pills is going to magically keep you from contracting the disease.

Stay safe!
Follow me on Twitter @ChrisPollyanna1 for the latest updates.
Please also join my longevity Facebook group.
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NOTE: I’ve been having trouble linking to the science journal hacking site www.sci-hub.se , so am only including Full Text links to articles not behind a paywall. I still have been able to download most of them, so if there are any that you are after, I can send them upon request, or you can simply copy the paper’s URL into the site above to get +95% of papers hidden behind paywalls.

Round-Up:

I truly believe that epigenetic reprogramming will be the next “big thing” in the ageing field and this paper is another early example of what will soon hopefully become a flood of papers. Here, the researchers found that using this method improved the cognitive performance of mice. This is the first time that its effects on the central nervous system had been checked.
Partial Cellular Reprogramming Improves Memory in Old Mice Full Text

Epigenetic reprogramming is some ways of in the future, so I wanted to show some examples of research which are much closer to fruition. In this first case it is a pilot study combining Resveratrol with exercise, which shows preliminary improvement in exercise endurance in the elderly.
*Resveratrol and exercise combined to treat functional limitations in late life: A pilot randomized controlled trial

Here is another study with near term applicability whereby the ingestion of a ketogenic drink improved cognition in those with mild cognitive impairment, lending further credence to the benefits of ketosis.
*A ketogenic drink improves cognition in mild cognitive impairment: Results of a 6-month RCT Full Text

There’s been recent controversy over whether or not Metformin is beneficial when combined with exercise, as it seems to prevent the gaining of muslce mass. However, in this study it seems to make gene expression more youthful.
*Metformin alters skeletal muscle transcriptome adaptations to resistance training in older adults Full Text

In 2012 a study came out which suggested that C60 could almost double the lifespan of a rat. Naturally, this caused quite a flurry of excitement and a number of people started taking it as a supplement. However, the study was very small and it behoves one to at least wait for replication before jumping on any bandwagon. After 8 years that replication finally happened and resulted in no improvement in lifespan as well as potential toxicity - demonstrating yet again that studies should never be taken in isolation.
C60 Does Not Improve Lifespan nor Healthspan Abstract

Covid-19 Longevity Related Papers:

2020 Supplemental Information

***Disclaimer 1 – As should be self-evident to anyone receiving these emails, 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 needing 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 below 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.*
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Lifestyle

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 from dawn to sunset for four consecutive weeks induces anticancer serum proteome response and improves metabolic syndrome Full Text
Comparative proteomics analysis of dietary restriction in Drosophila Full Text
Short-term protein restriction at advanced age stimulates FGF21 signalling, energy expenditure and browning of white adipose tissue Full Text

Diet – let food be thy medicine…
*Beneficial Role of Replacing Dietary Saturated Fatty Acids with Polyunsaturated Fatty Acids in the Prevention of Sarcopenia: Findings from the NU-AGE Cohort Full Text
*Green Tea, Coffee, and Mortality Risk in T2DM Full Text
Diet to Reduce the Metabolic Syndrome Associated with Menopause. The Logic for Olive Oil Full Text

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*Resistance training and health in adults: an overview of systematic reviews Full Text
*Effect of exercise training for five years on all cause mortality in older adults-the Generation 100 study: randomised controlled trial Full Text
*A systematic review of compositional data analysis studies examining associations between sleep, sedentary behaviour, and physical activity with health outcomes in adults Full Text

Non-prescription Supplements (in alphabetical order)
*Due to concerns about engendering homeostasis, I’ve begun varying my intake of supplements so that I’m not taking all of them every day. Haven’t worked out a rota so far.

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. I take 4 or 8 mg intermittently.
Isoproterenol-Induced Permeability Transition Pore-Related Dysfunction of Heart Mitochondria Is Attenuated by Astaxanthin Full Text
Biological effect of astaxanthin on alcohol-induced gut damage in Carassius auratus used as experimental model Full Text
Astaxanthin protects retinal ganglion cells from acute glaucoma via the Nrf2/HO-1 pathway

Curcumin – the spice which gives curries their yellow colour. Anti-inflammatory and neuroprotective. I take 1 gram intermittently. Needs to be taken with black pepper (piperine) to improve bioavailability.
*The effect of curcumin ointment on knee pain in older adults with osteoarthritis: a randomized placebo trial Full Text
*Evaluation of Cognitive Performance following Fish-Oil and Curcumin Supplementation in Middle-Aged and Older Adults with Overweight or Obesity
Curcumin reverses diabetic nephropathy in streptozotocin-induced diabetes in rats by inhibition of PKCβ/p 66 Shc axis and activation of FOXO-3a Full Text

Fisetin – a flavonoid found in highest concentrations in strawberries. Senolytic, anti-inflammatory, anti-cancer, neuro-protective & Sirt1 activator. I take 100mg intermittently and will soon be trying a high dose senolytic n=1 trial.
Fisetin Suppresses Pulmonary Inflammatory Responses through Heme Oxygenase-1 Mediated Downregulation of Inducible Nitric Oxide Synthase

Melatonin – a natural hormone produced in the pineal gland, it makes us get to sleep every night, but it has many other functions, including as a mitochondrial antioxidant. I’ve been taking 3mg for years before bed time purely as a sleep aid, but I’ve recently noticed it repeatedly cropping up in my longevity searches so decided to include it in its own section.
The melatonin metabolite N1-acetyl-5-methoxykynuramine facilitates long-term object memory in young and aging mice

Nicotinamide MonoNucleotide (NMN) – newer NAD+ precursor. I take 250 – 500mg on days I exercise.
Hyperglycemia-reduced NAD + biosynthesis impairs corneal epithelial wound healing in diabetic mice

Nicotinamide Riboside (NR) – NAD+ precursor.
*Boosting NAD level suppresses inflammatory activation of PBMCs in heart failure Full Text
Nicotinamide riboside reduces cardiometabolic risk factors and modulates cardiac oxidative stress in obese Wistar rats under caloric restriction
Deletion of CD38 and supplementation of NAD + attenuate axon degeneration in a mouse facial nerve axotomy model Full Text

Pterostilbene – found in blueberries. Anti-oxidant, anti-inflammatory and Sir1 activator. Similar to, but with greater bioavailability than resveratrol. Taking 50mg intermittently in the same pill as resveratrol. Works better in conjunction with NAD+ precursors.
Comparative Effects of Pterostilbene and Its Parent Compound Resveratrol on Oxidative Stress and Inflammation in Steatohepatitis Induced by High-Fat High-Fructose Feeding Full Text
Pterostilbene Exerts Hepatoprotective Effects through Ameliorating LPS/D-Gal-Induced Acute Liver Injury in Mice
Protective effects of pterostilbene against hepatic damage, redox imbalance, mitochondrial dysfunction, and endoplasmic reticulum stress in weanling piglets

Resveratrol – found in the skin of grapes. Anti-oxidant, anti-inflammatory and Sir1 activator. Taking 250mg intermittently in the same pill as pterostilbene. Works better in conjunction with NAD+ precursors & Spermidine.
Mechanisms of Aging and the Preventive Effects of Resveratrol on Age-Related Diseases Full Text
*Supplementation with Resveratrol, Piperine and Alpha-Tocopherol Decreases Chronic Inflammation in a Cluster of Older Adults with Metabolic Syndrome Full Text
*Supplementation with Red Wine Extract Increases Insulin Sensitivity and Peripheral Blood Mononuclear Sirt1 Expression in Nondiabetic Humans Full Text

Spermidine – found in wheat germ and a potent inducer of autophagy, it works in synergy with Resveratrol. I try to eat a few teaspoons of wheat germ every day in my berry & nut breakfast.
Voluntary activity reverses spermidine-induced myocardial fibrosis and lipid accumulation in the obese male mouse
Spermidine endows macrophages anti-inflammatory properties by inducing mitochondrial superoxide-dependent AMPK activation, Hif-1α upregulation and autophagy

Other available supplements (in alphabetical order) & combinations
Antioxidant Activity with Increased Endogenous Levels of Vitamin C, E and A Following Dietary Supplementation with a Combination of Glutathione and Resveratrol Precursors
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Diabetes medications as potential calorie restriction mimetics-a focus on the alpha-glucosidase inhibitor acarbose
Carnosine attenuates vascular smooth muscle cells calcification through mTOR signaling pathway Full Text
1,25(OH) 2 D 3 ameliorates palmitate-induced lipotoxicity in human primary osteoblasts leading to improved viability and function
Vitamin D and its Effects on DNA Methylation in Development, Aging, and Disease
Vitamin D and Sarcopenia: Potential of Vitamin D Supplementation in Sarcopenia Prevention and Treatment Full Text
Effects of Ginkgo biloba intake on cardiometabolic parameters in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of clinical trials
Anti-aging effect of DL-β-hydroxybutyrate against hepatic cellular senescence induced by D-galactose or γ-irradiation via autophagic flux stimulation in male rats Full Text
The effects of six months Persicaria minor extract supplement among older adults with mild cognitive impairment: a double-blinded, randomized, and placebo-controlled trial Full Text

Prescription Supplements
Metformin – Anti-diabetic medication, maintained by many scientists to be a safe longevity enhancing medication. I’m still on the fence about this.
*Long-term metformin treatment and risk of peripheral neuropathy in older Veterans
Metformin rescues Parkinson's disease phenotypes caused by hyperactive mitochondria Full Text
Targeting ageing and preventing organ degeneration with metformin

Rapamycin (sirolimus) – first drug proven to increase the health & lifespan of mice. Currently used for organ transplantation and against cancer.
Effect of rapamycin on aging and age-related diseases-past and future Full Text
Combined application of rapamycin and atorvastatin improves lipid metabolism in apolipoprotein E-deficient mice with chronic kidney disease Full Text
Role of exercise and rapamycin on the expression of energy metabolism genes in liver tissues of rats fed a high‑fat diet Full Text

Other Areas of Interest (in alphabetical order)
Ageing Clocks & other biomarkers of ageing – the ability to measure biological ageing is crucial if we don’t want to have to wait 20+ years for the results of an anti-ageing intervention:
Data mining of human plasma proteins generates a multitude of highly predictive aging clocks that reflect different aspects of aging Full Text
Blood-based biomarkers in hypothalamic-pituitary axes for the risk of dementia or cognitive decline: a systematic review and meta-analysis Full Text
Sex-related differences in behavioural markers in adult mice for the prediction of lifespan

Epigenetic Cellular Reprogramming – the next big thing in longevity science as far as I am concerned & the closest thing we might have to a silver bullet against ageing. It involves targeting the epigenome:
The influences of DNA methylation and epigenetic clocks, on metabolic disease, in middle-aged Koreans Full Text
Genetic and environmental causes of variation in epigenetic aging across the lifespan Full Text

Exosomes - small packets of information released by cells.
Blood extracellular vesicles from healthy individuals regulate hematopoietic stem cells as humans age Full Text canada
Rejuvenation of mesenchymal stem cells by extracellular vesicles inhibits the elevation of reactive oxygen species Full Text
Comparison of exosomes derived from induced pluripotent stem cells and mesenchymal stem cells as therapeutic nanoparticles for treatment of corneal epithelial defects Full Text

Genetics
SynergyAge, a curated database for synergistic and antagonistic interactions of longevity-associated genes Full Text
Genetic differences and longevity-related phenotypes influence lifespan and lifespan variation in a sex-specific manner in mice Full Text
APOE2 is associated with longevity independent of Alzheimer's disease Full Text

Lifespan Lengthening Interventions - any intervention which lengthens the lifespan and/or healthspan of model organisms.
Drosophila Caliban preserves intestinal homeostasis and lifespan through regulating mitochondrial dynamics and redox state in enterocytes
Healthful Aging Mediated by Inhibition of Oxidative Stress
Composition of peony petal fatty acids and flavonoids and their effect on Caenorhabditis elegans lifespan
Effects of ethyl acetate fractional extract from Portulaca oleracea L. (PO-EA) on lifespan and healthspan in Caenorhabditis elegans

Microbiome – all the little critters living in and on us have a major influence on our health and potentially our longevity.
Could a poo transplant one day be the secret of eternal youth? Full Text
The aging mouse microbiome has obesogenic characteristics Full Text
Gut microbiota ecology: Biodiversity estimated from hybrid neutral-niche model increases with health status and aging Full Text

Miscellaneous Molecules
Mitochondria-Targeted Small Peptide, SS31 Ameliorates Diabetes Induced Mitochondrial Dynamics in Male TallyHO/JngJ Mice
Klotho ameliorates diabetic nephropathy via LKB1-AMPK-PGC1α-mediated renal mitochondrial protection
17α-Estradiol prevents ovariectomy-mediated obesity and bone loss Full Text
Sulforaphane prevents age-associated cardiac and muscular dysfunction through Nrf2 signaling Full Text

Senolytics – not supplements or available now, but the most exciting area of anti-research at the moment involving the removal of senescent cells:
Advancements in therapeutic drugs targeting of senescence Full Text

Skin & Beauty – not naming any names, but I’m sure that some of you also care about superficial ageing – how our skin looks. ;-) Having said that, it is our largest organ & the treatments which keep on cropping up could be of use to some people.
*Safety and Efficacy of Oral Intake of Ceramide-Containing Acetic Acid Bacteria for Improving the Stratum Corneum Hydration: A Randomized, Double-Blind, Placebo-Controlled Study over 12 Weeks Full Text
*A serum containing vitamins C & E and a matrix-repair tripeptide reduces facial signs of aging as evidenced by Primos® analysis and frequently repeated auto-perception Full Text
*Randomized controlled study for the anti-aging effect of human adipocyte-derived mesenchymal stem cell media combined with niacinamide after laser therapy

Stem Cells
Mesenchymal stem cells alleviate LPS-induced acute lung injury by inhibiting the proinflammatory function of Ly6C + CD8 + T cells Full Text
Chondroprotective Effects of Combination Therapy of Acupotomy and Human Adipose Mesenchymal Stem Cells in Knee Osteoarthritis Rabbits via the GSK3β-Cyclin D1-CDK4/CDK6 Signaling Pathway Full Text
Neuroprotective effects of human amniotic fluid stem cells-derived secretome in an ischemia/reperfusion model Full Text

Telomeres – the protective caps on the end of our chromosomes. Their shortening over time has been seen by some as either an ageing “clock”, or indeed as a driver of ageing itself, however, this is a controversial viewpoint.
Telomere length and its relationships with lifestyle and behavioural factors: variations by sex and race/ethnicity Full Text
Association between genetically predicted telomere length and facial skin aging in the UK Biobank: a Mendelian randomization study Full Text
Mathematical Connection between Short Telomere Induced Senescence Calculation and Mortality Rate Data Full Text

Young Blood Factors or other heterochronic transplantation – another potential “silver bullet” against ageing based on the discovery that young blood seems to rejuvenate older animals and vice versa. The race is on to discover what components in blood cause these changes and if they can be applied to humans:
Candidate rejuvenating factor GDF11 and tissue fibrosis: friend or foe? Full Text
Age-related CCL12 Aggravates Intracerebral Hemorrhage-induced Brain Injury via Recruitment of Macrophages and T Lymphocytes Full Text