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March 2020 Longevity Review

Posted by Chris Pollyanna , 12 April 2020 · 1,443 views

longevity review supplements rapamycin resveratrol crispr covid19 stem cells nad+ senolytics

March 2020 Longevity Review


Hello and welcome again to this month’s longevity review. Things have certainly changed since we last met - everyone's lives have been turned upside down and whatever plans we had for the year have been put into stasis. The longevity field is no exception: labs have shut, experiments cancelled, and conferences postponed. What medium term impact this will have is impossible to ascertain and pointless to even hazard a guess. However, the long term trajectory will be unaffected - regardless of the shape of the COVID curve, I still believe that ageing will have come under our control within the next twenty years, as the momentum which has built up is not easily derailed. In fact, impetus might be added with the realisation that COVID-19 would merely be a minor curiosity in an obscure virological journal if everyone had the immune system of a twenty-year-old and “pre-existing conditions” had been eradicated.


Although a lot of longevity research has come to a screeching halt, the time delay inherent in scientific publication ensures that there will still be a steady stream of discoveries being announced for the foreseeable future. I have added a COVID-19 section to the News Round-Up, to give a flavour of how the longevity field is pivoting to confront this menace, but bear in mind that the pace of research into COVID-19 means that it will be most likely out of date and it is not meant to provide any practical advice. For the latest in COVID-19 related research, check out LEAF’s COVID-19 THERAPEUTICS ROADMAP


Personally, I am fortunate for now at least to still have a job, though online teaching has proven to be more demanding and exhausting than I could possibly have imagined. Finding time for longevity research and advocacy is challenging.


Lastly, be thankful that we live in the year 2020, for the knowledge & capabilities of science has never been greater and speed at which COVID-19 will eventually be vanquished will have never been swifter.


Most of all - Stay Safe!


Follow me on Twitter @ChrisPollyanna1 for the latest updates.


Or you can find them on my longevity Facebook group, which I hope you will also join.


Finally – please post any comments in the comment section at the bottom - all feedback is greatly appreciated. :-D
NOTE: I’ve been having trouble linking to the science journal hacking site www.sci-hub.tw , 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.


March Round-Up:


Reprogramming cells back into a youthful state is going to be the next big thing after senolytics in the longevity field, and the paper here shows a new method of doing so. Although so far only in humans cells, it gives a tantalising glimpse at was is in store:
Reversing Cellular Aging Takes Another Step Forward Full Text


Here, a naturally occurring enzyme is shown to improve the gut barrier function and as a consequence improved the frailty and lifespan of mice and flies. As it is natural and has already been safely administered to humans in a trial for ulcerative colitis, it should have a quicker path to the clinic for longevity purposes:
Gut enzyme IAP found to prevent aging and frailty in animal models Full Text


In this paper it has been shown once again the rejuvenatory powers of young blood plasma when given to older mice. This time the young plasma reversed the transcriptomal signatures of normal ageing in the capillaries of the brain:
Brain Endothelial Cells Are Exquisite Sensors of Age-Related Circulatory Cues. Full Text


CRISPR/Cas9, which is the current star of the gene editing field, has here been used to prevent muscle wasting and loss of strength in mice. Unlike conventional drugs, treatments would only have to be given once:
CRISPR/Cas9-Mediated miR-29b Editing as a Treatment of Different Types of Muscle Atrophy in Mice. Full Text


Finally, in this paper, Induced Pluripotent Stem Cells have been used to regenerate blood vessels in the mouse eye with a greater efficiency than has previously been possible:
Primitive Stem Cells Regenerate Blood Vessels in the Eye Full Text


Covid-19 Longevity Related Papers:
Geroprotective and senoremediative strategies to reduce the comorbidity, infection rates, severity, and lethality in gerophilic and gerolavic infections. Full Text
COVID-19 and chronological aging: senolytics and other anti-aging drugs for the treatment or prevention of corona virus infection? Full Text
Transplantation of ACE2- Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia. Full Text
Further sources of information:
Fight Aging! (quite opinionated about the damage theory of ageing)
Life Extension Advocacy Foundation (LEAF) (best source of longevity information on the web)
Longecity (good forums where the self-experimenters reside!)
Aging Matters (good blog from the programmed ageing side)
Research Institutes:
SENS Research Foundation (I have a recurring monthly donation)
Buck Institute


Private initiatives:
Age-Reversal Network (good information & forums for those interested in self-experimentation – this is where I found how to get non-prescription Rapamycin)
Better Humans
Gerontology Research Group
Lifespan.io (Tied together with LEAF, I have a recurring monthly donation)



March 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.*


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.
*Dietary restriction for prevention of contrast-induced acute kidney injury in patients undergoing percutaneous coronary angiography: a randomized controlled trial. Full Text
*Fasting for stem cell rejuvenation Full Text
*Changes in body weight, adherence, and appetite during 2 years of calorie restriction: the CALERIE 2 randomized clinical trial.
*Reduced caloric intake and periodic fasting independently contribute to metabolic effects of caloric restriction. Full Text
*Determinants of Adherence in Time-Restricted Feeding in Older Adults: Lessons from a Pilot Study. Full Text


Dietlet food be thy medicine…
*Fish Intake May Affect Brain Structure and Improve Cognitive Ability in Healthy People. Full Text *Self-Reported Omega-3 Supplement Use Moderates the Association between Age and Exercising Cerebral Blood Flow Velocity in Older Adults. Full Text
*Associations of habitual fish oil supplementation with cardiovascular outcomes and all cause mortality: evidence from a large population based cohort study. Full Text
*Dietary and Serum Omega-6/Omega-3 Fatty Acids Are Associated with Physical and Metabolic Function in Stroke Survivors. Full Text
Green Tea Catechins Trigger Immediate-Early Genes in the Hippocampus and Prevent Cognitive Decline and Lifespan Shortening.


Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*A Cross-Sectional Study Evaluating the Effects of Resistance Exercise on Inflammation and Neurotrophic Factors in Elderly Women with Obesity. Full Text
*Effects of simultaneous cognitive and aerobic exercise training on dual-task walking performance in healthy older adults: results from a pilot randomized controlled trial. Full Text
*How Physical Activity across the Lifespan Can Reduce the Impact of Bone Ageing: A Literature Review. Full Text
*The Effect of 12 Weeks of Different Exercise Training Modalities or Nutritional Guidance on Cardiometabolic Risk Factors, Vascular Parameters, and Physical Fitness in Overweight Adults: Cardiometabolic High-Intensity Interval Training-Resistance Training Randomized Controlled Study.


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 carotinoid, it has anti-oxidative, anti-inflamatory, anti-cancer, neuro-protective and skin-protective qualities. I take 4 or 8 mg intermittently.
*Effects of Astaxanthin Supplementation on Skin Health: A Systematic Review of Clinical Studies.
Combination therapy with astaxanthin and epidermal neural crest stem cells improves motor impairments and activates mitochondrial biogenesis in a rat model of spinal cord injury.
Astaxanthin Protects Ochratoxin A-Induced Oxidative Stress and Apoptosis in the Heart via the Nrf2 Pathway. Full Text Protective Effect of Astaxanthin on Ochratoxin A-Induced Kidney Injury to Mice by Regulating Oxidative Stress-Related NRF2/KEAP1 Pathway. Full Text Astaxanthin (ATX) enhances the intestinal mucosal functions in immunodeficient mice.


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 bio-availability.
*Impact of curcumin supplementation on expression of inflammatory transcription factors in hemodialysis patients: A pilot randomized, double-blind, controlled study.
*The Effect of Curcumin Supplementation and Aerobic Training on Anthropometric Indices Serum Lipid Profiles, C-Reactive Protein and Insulin Resistance in Overweight Women: A Randomized, DoubleBlind, Placebo-Controlled Trial.
*Herbal formulation "turmeric extract, black pepper, and ginger" versus Naproxen for chronic knee osteoarthritis: A randomized, double-blind, controlled clinical trial.
*Aerobic exercise and nano-curcumin supplementation improve inflammation in elderly females with metabolic syndrome. Full Text
Curcumin in Health and Diseases: Alzheimer's Disease and Curcumin Analogues, Derivatives, and Hybrids. Full Text


Fisetin – a flavonoid found in highest concentration 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 Prevents HT22 Cells From High Glucose-Induced Neurotoxicity via PI3K/Akt/CREB Signaling Pathway. Full Text
Protective effects of fisetin against myocardial ischemia/reperfusion injury. Full Text


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 anti-oxidant. 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.
Melatonin inhibits cytosolic mitochondrial-DNA induced neuroinflammatory signaling in accelerated aging and neurodegeneration. Full Text
Melatonin and cannabinoids: mitochondrial-targeted molecules that may reduce inflammaging in neurodegenerative diseases. Full Text
Mitochondrial dysfunction in age-related macular degeneration: melatonin as a potential treatment.


Nicotinamide MonoNucleotide (NMN) – newer NAD+ precursor. I take 250 – 500mg on days I exercise.
Administration of Nicotinamide Mononucleotide (NMN) Reduces Metabolic Impairment in Male Mouse Offspring from Obese Mothers.


Nicotinamide Riboside (NR) – NAD+ precursor.
Nicotinamide riboside protects noise-induced hearing loss by recovering the hair cell ribbon synapses.


Pterostilbene – found in blueberries. Anti-oxidant, anti-inflamatory 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.
Pterostilbene improves cardiac function in a rat model of right heart failure through modulation of calcium handling proteins and oxidative stress.
Effects of resveratrol and its derivative pterostilbene on brown adipose tissue thermogenic activation and on white adipose tissue browning process.
Pterostilbene Inhibits FcεRI Signaling through Activation of the LKB1/AMPK Pathway in Allergic Response.


Resveratrol – found in the skin of grapes. Anti-oxidant, anti-inflamatory and Sir1 activator. Taking 250mg intermittently in the same pill as pterstilbene. Works better in conjunction with NAD+ precursors & Spermidine.
*Sustained Cerebrovascular and Cognitive Benefits of Resveratrol in Postmenopausal Women. Full Text
*The effect of resveratrol supplementation on serum levels of asymmetric de-methyl-arginine and paraoxonase 1 activity in patients with type 2 diabetes: A randomized, double-blind controlled trial.
Health Benefits and Molecular Mechanisms of Resveratrol: A Narrative Review. Full Text
Potential Adverse Effects of Resveratrol: A Literature Review. Full Text
Resveratrol decreases cell apoptosis through inhibiting DNA damage in bronchial epithelial cells. Full Text
Resveratrol and its Related Polyphenols Contribute to the Maintenance of Genome Stability. Full Text


Other available supplements or Combinations of above
*An Evaluation of a Nutraceutical with Berberine, Curcumin, Inositol, Banaba and Chromium Picolinate in Patients with Fasting Dysglycemia. Full Text


Prescription Supplements


MetforminAnti-diabetic medication, maintained by many scientists to be a safe longevity enhancing medication. I’m still on the fence about this.
*Metformin and heart failure-related outcomes in patients with or without diabetes: a systematic review of randomized controlled trials.
Exploring the Comparative Efficacy of Metformin and Resveratrol in the Management of Diabetes-associated Complications: A Systematic Review of Preclinical Studies. Full Text
Metformin inhibits high glucose-induced smooth muscle cell proliferation and migration. Full Text
Metformin reduces aging-related leaky gut and improves cognitive function by beneficially modulating gut microbiome/goblet cell/mucin axis.


Rapamycin (sirolimus) – first drug proven to increase the health & lifespan of mice. Currently used for organ transplantation and against cancer.
Transient and late-life rapamycin for healthspan extension Full Text
APOE genotype-dependent pharmacogenetic responses to rapamycin for preventing Alzheimer's disease. Full Text
Rapamycin protects chondrocytes against IL-18-induced apoptosis and ameliorates rat osteoarthritis. Full Text
Autophagy and mTOR signaling during intervertebral disc aging and degeneration. Full Text
Everolimus Rescues the Phenotype of Elastin Insufficiency in Patient Induced Pluripotent Stem Cell-Derived Vascular Smooth Muscle Cells. Full Text


Other Areas of Interest


Senolytics & Senescent Cellsnot supplements or available now, but the most exciting area of anti-research at the moment. I intend to take the plunge into senolytics within the next year, before giving them to my parents:
The senotherapeutic drug ABT-737 disrupts aberrant p21 expression to restore liver regeneration in adult mice.
Cellular Senescence as a Therapeutic Target for Age-Related Diseases: A Review. Full Text
Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases. Full Text
The Emerging Role of Senescence in Ocular Disease. Full Text
Survey of senescent-cell markers with age in human tissues. Full Text


Ageing Clocks & other Biomarkers of Ageingthe 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:
DNA Methylation Biomarkers in Aging and Age-Related Diseases. Full Text
Plasma proteomic signature of the risk of developing mobility disability: A 9-year follow-up. Full Text
Blood DNA Methylation and Aging: A Cross-Sectional Analysis and Longitudinal Validation in the InCHIANTI Study.
AgeGuess, a Methylomic Prediction Model for Human Ages. Full Text
Age-Associated DNA Methylation Patterns Are Shared Between the Hippocampus and Peripheral Blood Cells. 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.
Leukocyte Telomere Length Independently Predicts 3-Year Diabetes Risk in a Longitudinal Study of Chinese Population. Full Text
Can telomere length predict bone health? A review of current evidence. Full Text
Telomere shortening reflecting physical aging is associated with cognitive decline and dementia conversion in mild cognitive impairment due to Alzheimer's disease. Full Text


Microbiome – all the little critters living in and on us have a major influence on our health and potentially our longevity.
Transplant of microbiota from long-living people to mice reduces aging-related indices and transfers beneficial bacteria. Full Text
Genetic influences of the microbiota on Drosophila melanogaster lifespan.
Bacteria Boost Mammalian Host NAD Metabolism by Engaging the Deamidated Biosynthesis Pathway.
Shotgun Metagenomics of Gut Microbiota in Humans with up to Extreme Longevity and the Increasing Role of Xenobiotic Degradation. Full Text
Adjusting for age improves identification of gut microbiome alterations in multiple diseases. Full Text


Stem Cells & Exosomes (small packets of information released by cells)
Exosomes From Induced Pluripotent Stem Cell-Derived Cardiomyocytes Promote Autophagy for Myocardial Repair. Full Text
Potential of mesenchymal stem cells alone, or in combination, to treat traumatic brain injury. Full Text
Stem Cell Aging in Skeletal Muscle Regeneration and Disease. Full Text
miR-155-5p inhibition rejuvenates aged mesenchymal stem cells and enhances cardioprotection following infarction. Full Text
Extracellular Vesicles Derived From Mesenchymal Stem Cells (MSC) in Regenerative Medicine: Applications in Skin Wound Healing. Full Text


Young Blood Factors or other Heterochronic Transplantations 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:
Circulating anti-geronic factors from heterochonic parabionts promote vascular rejuvenation in aged mice: transcriptional footprint of mitochondrial protection, attenuation of oxidative stress, and rescue of endothelial function by young blood.


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.
Diet and Skin Aging-From the Perspective of Food Nutrition. Full Text
An Anti-Wrinkle Diet: Nutritional Strategies to Combat Oxidation, Inflammation and Glycation Full Text
Advanced Glycation End Product Inhibition by Alkaloids from Ocotea paranapiacabensis for the Prevention of Skin Aging.
Organotypic human skin culture models constructed with senescent fibroblasts show hallmarks of skin aging. Full Text
Human umbilical cord mesenchymal stem cell-derived and dermal fibroblast-derived extracellular vesicles protect dermal fibroblasts from ultraviolet radiation-induced photoaging in vitro.


Odds & Sods
Ginsenoside Rb1 retards aging process by regulating cell cycle, apoptotic pathway and metabolism of aging mice.
Exogenous GDF11, but not GDF8, reduces body weight and improves glucose homeostasis in mice. Full Text
Inhibition of histone acetyltransferase GCN5 extends lifespan in both yeast and human cell lines. Full Text
Verapamil extends lifespan in Caenorhabditis elegans by inhibiting calcineurin activity and promoting autophagy. Full Text
The Immune Response Against Human Cytomegalovirus Links Cellular to Systemic Senescence. Full Text
Randomized placebo-controlled trial of the effects of aspirin on dementia and cognitive decline.
The JAK1/2 inhibitor ruxolitinib delays premature aging phenotypes. Full Text
NoxO1 Knockout Promotes Longevity in Mice. Full Text
DNA methylation clocks as a predictor for ageing and age estimation in naked mole-rats, Heterocephalus glaber. Full Text
Probiotics modulate the microbiota-gut-brain axis and improve memory deficits in aged SAMP8 mice. Full Text

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