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May 2021 Longevity Review

Posted by Chris Pollyanna , 11 June 2021 · 1,410 views

supplements lifestyle fasting rapamycin metformin nmn

Hello and welcome again to this month’s longevity review. By far the most important longevity news this past month was the launch of the PEARL crowdfunding campaign, which seeks to test Rapamycin in humans. Rapamycin was the first drug proven to extend the lifespan of mammals, as well as improving their general health. However, we need to find out if the same applies to humans, which is exactly what this crowdfunding campaign will find out. That’s why I think this is the world’s most important clinical trial. What other drug could potentially cut your risk of getting Alzheimer’s, cancer and heart disease at the same time? And did I mention it could also improve vaccine response by strengthening the immune system?

 

So please, whatever your financial position, consider donating towards this groundbreaking campaign! They have already reached their initial and first stretch goal, but if their final stretch goal is reached, then they can run even more tests and find out even more useful information.

 

PEARL: PARTICIPATORY EVALUATION OF AGING WITH RAPAMYCIN FOR LONGEVITY

 

Follow me on Twitter @ChrisPollyanna1 for the latest updates.

 

The Canadian Longevity Association website continues to grow with the addition of a News page.
For previous Longevity Reviews, they can be found on the Canadian Longevity Association Facebook group, which I hope you will also join.
A reminder that you can show your support via my Patreon account, which includes bonus material for members.

 

Stay safe!
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Round-Up:

 

Time restricted eating is a form of fasting where your daily calories are consumed within a certain window, typically between 6 - 12 hours. The health effects in mice are remarkable, and now studies such as this are starting to show similar benefits in humans. Here, combined with exercise, it led to reduced fat and increased muscle mass.
*Time-restricted eating and concurrent exercise training reduces fat mass and increases lean mass in overweight and obese adults Full Text

 

Partial epigenetic reprogramming is the next big thing in longevity research and the number of studies are finally starting to increase. Here, the technique was used to improve muscle regeneration.
How to boost muscle regeneration and rebuild tissue Full Text

 

Stem cells continue to attract interest for their therapeutic potential, but it is becoming increasingly clear that the molecules they release are even more interesting. Here, their extracellular vesicles are shown to improve degenerative disc disease in mice.
Induced pluripotent stem cell-derived mesenchymal stem cells deliver exogenous miR-105-5p via small extracellular vesicles to rejuvenate senescent nucleus pulposus cells and attenuate intervertebral disc degeneration Full Text

 

New ways to remove senescent cells continue to be found. In this study, researchers were able to induce natural killer T cells to clear out senescent cells, which resulted in improved glycemic control and lung fibrosis.
Scientists find mechanism that eliminates senescent cells Full Text

 

Covid-19 Longevity Related Paper:
Curcumin as a Potential Treatment for COVID-19 Full Text
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Videos to watch:
Another YouTube channel with interviews with leading longevity researchers:

 

Foresight Institute - Biotech & Health Extension Focus
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Further sources of information:
Fight Aging! (quite opinionated about the damage theory of ageing)
Life Extension Advocacy Foundation (LEAF)/Lifespan.io (best source of longevity information on the web & I volunteer for them)

Research Institutes:
SENS Research Foundation
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

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2021 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 you need medical advice.***

 

**Disclaimer 2In 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.
*Effects of intermittent (5:2) or continuous energy restriction on basal and postprandial metabolism: a randomised study in normal-weight, young participants Full Text
*The impact of Ramadan fasting on Fetuin-A level in type 2 diabetes mellitus Full Text

 

Diet – let food be thy medicine…
*One cup of leafy green vegetables a day lowers risk of heart disease Full Text
*The role of diet quality and dietary patterns in predicting muscle mass and function in men over a 15-year period Full Text
*Adherence to dietary guidelines and cognitive decline from middle age: the Doetinchem Cohort Study Full Text

 

Exercise if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*Effects of exercise on cellular and tissue aging Full Text
*Light-Intensity Physical Activity and Life Expectancy: National Health and Nutrition Survey
*Different physical activity 'cocktails' have similar health benefits 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.
Effects of astaxanthin in animal models of obesity-associated diseases: A systematic review and meta-analysis
Astaxanthin and Nrf2 signaling pathway: a novel target for new therapeutic approaches

 

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 Effects of Curcumin on Diabetes Mellitus: A Systematic Review Full Text
*A Systematic Review Assessing Clinical Utility of Curcumin with a Focus on Cancer Prevention Full Text
*The efficacy and safety of Curcuma longa Extract and curcumin supplements on osteoarthritis: a systematic review and meta-analysis Full Text

 

Fisetin a flavonoid found in highest concentrations in strawberries. Senolytic, anti-inflammatory, anti-cancer, neuro-protective & Sirt1 activator. I take 100mg intermittently.
Fisetin mitigates hepatic ischemia-reperfusion injury by regulating GSK3β/AMPK/NLRP3 inflammasome pathway

 

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 take 3mg every night primarily as a sleep aid.
*Melatonin and Cardioprotection in Humans: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
*Neurocognitive effects of melatonin treatment in healthy adults and individuals with Alzheimer's disease and insomnia: a systematic review and meta-analysis of randomized controlled trials Full Text
*Melatonin and the health of menopausal women: a systematic review Full Text

 

Nicotinamide MonoNucleotide (NMN) newer NAD+ precursor. I take 250 – 500mg on days I exercise.
Preconditioning of mesenchymal stem cells with ghrelin exerts superior cardioprotection in aged heart through boosting mitochondrial function and autophagy flux

 

Nicotinamide Riboside (NR) NAD+ precursor.
Nicotinamide Riboside Rejuvenates Blood Stem Cells in Mice Full Text
Nicotinamide Riboside Enhances Endothelial Precursor Cell Function to Promote Refractory Wound Healing Through Mediating the Sirt1/AMPK Pathway 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.
The in vitro and in vivo depigmenting activity of pterostilbene through induction of autophagy in melanocytes and inhibition of UVA-irradiated α-MSH in keratinocytes via Nrf2-mediated antioxidant pathways Full Text

 

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.
*No effect of resveratrol in patients with mitochondrial myopathy: a cross-over randomized controlled trial
The impact of resveratrol on skin wound healing, scarring, and aging Full Text
Cardioprotection stimulated by resveratrol and grape products prevents lethal cardiac arrhythmias in an animal model of ischemia and reperfusion 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.
Spermidine inhibits vascular calcification in chronic kidney disease through modulation of SIRT1 signaling pathway Full Text
Antioxidant Effect of Wheat Germ Extracts and Their Antilipidemic Effect in Palmitic Acid-Induced Steatosis in HepG2 and 3T3-L1 Cells Full Text

 

Other available supplements (in alphabetical order)
What is alpha-ketoglutarate? A Summary of AKG
Apigenin Alleviates Oxidative Stress-Induced Cellular Senescence via Modulation of the SIRT1-NAD[Formula: see text]-CD38 Axis
*Coenzyme Q10: Clinical Applications beyond Cardiovascular Diseases Full Text
What is Glucosamine? A Summary of Glucosamine
Intron retention as a new pre-symptomatic marker of aging and its recovery to the normal state by a traditional Japanese multi-herbal medicine Full Text
*Low Dose Lithium Treatment of Behavioral Complications in Alzheimer's Disease: Lit-AD Randomized Clinical Trial
Lutein Has a Positive Impact on Brain Health in Healthy Older Adults: A Systematic Review of Randomized Controlled Trials and Cohort Studies Full Text
*Omega-3 supplementation and heart failure: A meta-analysis of 12 trials including 81,364 participants
*Intranasal Oxytocin Improves Lean Muscle Mass and Lowers LDL Cholesterol in Older Adults with Sarcopenic Obesity: A Pilot Randomized Controlled Trial
*Safety and tolerability of chronic intranasal oxytocin in older men: results from a randomized controlled trial Full Text
Mechanistic insights and perspectives involved in neuroprotective action of quercetin Full Text
Quercetin Alleviates Intervertebral Disc Degeneration by Modulating p38 MAPK-Mediated Autophagy Full Text
*Impact of the Natural Compound Urolithin A on Health, Disease, and Aging Full Text
*The effect of zinc supplementation on fatigue among elderly community dwellers: A parallel clinical trial Full Text

 

Combinations of Supplements
Ginsenoside Rg1 and astaxanthin act on the hypothalamus to protect female mice against reproductive aging Full Text
Carotenoids supplementation and inflammation: a systematic review and meta-analysis of randomized clinical trials

 

Prescription Supplements
Metformin – Anti-diabetic medication, maintained by many scientists to be a safe longevity enhancing medication.
*MicroRNAs modulation and clinical outcomes at 1 year of follow-up in obese patients with pre-diabetes treated with metformin vs. placebo
*Acute metformin administration increases mean power and the early power phase during a Wingate test in healthy male subjects
*Metformin: Experimental and Clinical Evidence for a Potential Role in Emphysema Treatment

 

Rapamycin (sirolimus) – first drug proven to increase the health & lifespan of mice. Currently used for organ transplantation and against cancer.
*Clinical trials of mTOR inhibitors to boost immunity to viral infection in older adults Full Text
*Human Trials of mTOR Inhibitors for Immune Aging Full Text
Rapamycin Improves How Our DNA Is Stored Full Text
Genotype and Trait Specific Responses to Rapamycin Intake in Drosophila melanogaster Full Text

 

Other Areas of Interest (in alphabetical order)

 

Ageing Clocks & other Biomarkers of Ageing
*Twin Study Shows That Diet and Exercise Lower Biological Age Full Text
*Resilience as a New Measure of Biological Age Full Text
*Heavy Alcohol Use Linked to Greater Epigenetic Age in Women Full Text

 

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
The effect of aging on the bone healing properties of blood plasma
Aged hematopoietic stem cells are refractory to bloodborne systemic rejuvenation interventions

 

Epigenetics & Cellular Reprogramming
*Epigenome-wide association meta-analysis of DNA methylation with coffee and tea consumption Full Text
*Genome-wide associations between alcohol consumption and blood DNA methylation: evidence from twin study

 

Exosomes (small packets of information released by cells)
hAECs and their exosomes improve cardiac function after acute myocardial infarction in rats Full Text
Extracellular Vesicles from Mesenchymal Stem Cells as Potential Treatments for Osteoarthritis Full Text

 

Genetics including CRISPR
*People Living 105+ Years Appear to Repair DNA Better Full Text
Longevity pathways are associated with human ovarian ageing Full Text
Functional conservation in genes and pathways linking ageing and immunity Full Text

 

Lifespan Lengthening Interventions
Restoration of energy homeostasis by SIRT6 extends healthy lifespan Full Text
Ganoderma lucidum stimulates autophagy-dependent longevity pathways in Caenorhabditis elegans and human cells Full Text
Extreme lifespan extension in tapeworm-infected ant workers Full Text
Supplementation with phosphatidylethanolamine confers anti-oxidant and anti-aging effects via hormesis and reduced insulin/IGF-1-like signaling in C. elegans
A small-molecule Psora-4 acts as a caloric restriction mimetic to promote longevity in C. elegans
Saponins isolated from Radix polygalae extent lifespan by modulating complement C3 and gut microbiota
Weissella confusa CGMCC 19,308 Strain Protects Against Oxidative Stress, Increases Lifespan, and Bacterial Disease Resistance in Caenorhabditis elegans

 

Microbiome
*Researchers discover a gut microbiota profile that can predict mortality Full Text
Gut microbial involvement in Alzheimer's disease pathogenesis Full Text
The symbiotic relationship between Caenorhabditis elegans and members of its microbiome contributes to worm fitness and lifespan extension Full Text

 

Miscellaneous Molecules
Adalimumab ameliorates memory impairments and neuroinflammation in chronic cerebral hypoperfusion rats Full Text
Activation of monoaminergic system contributes to the antidepressant- and anxiolytic-like effects of J147
'Rejuvenating' the Alzheimer's brain Full Text

 

Observational Studies
*Amazon indigenous group's lifestyle may hold a key to slowing down aging Abstract
*The rate by which mortality increase with age is the same for those who experienced chronic disease as for the general population Full Text
*Biomarkers representing key aging-related biological pathways are associated with subclinical atherosclerosis and all-cause mortality: The Framingham Study Full Text

 

Opinion/Editorials/Theory
The plasticity of ageing and the rediscovery of ground-state prevention Full Text
Molecular evolution and the decline of purifying selection with age Full Text
Predation has small, short-term, and in certain conditions random effects on the evolution of aging Full Text

 

Other Ageing Biology
Interactions among mTORC, AMPK and SIRT: a computational model for cell energy balance and metabolism Full Text
Acceleration of ageing via disturbing mTOR-regulated proteostasis by a new ageing-associated gene PC4 Full Text
SIRT6 Linked to Slower Aging in Mice Full Text

 

Reviews
The regulation of healthspan and lifespan by dietary amino acids Full Text
*Sex differences in biological aging with a focus on human studies Full Text
Alternative Animal Models of Aging Research Full Text

 

Senolytics/Senescent Cells
The Senolytic Drug JQ1 Removes Senescent Cells via Ferroptosis
Researchers identify target for senolytic drugs Abstract
Cellular senescence as a driver of cognitive decline triggered by chronic unpredictable stress Full Text

 

Skin & Beauty
*Efficacy of fractional laser, radiofrequency and IPL rejuvenation of periorbital region Full Text
Role of ingestible carotenoids in skin protection: A review of clinical evidence Full Text
Extracellular Vesicles as Potential Theranostic Platforms for Skin Diseases and Aging Full Text

 

Stem Cells
Therapeutic Potential of HUMSCs in Female Reproductive Aging Full Text
Potential of Mesenchymal Stem Cells in the Rejuvenation of the Aging Immune System Full Text
Removing and Replacing Mitochondria in Human Cells Full Text

 

Telomeres
*The Effect of Alcohol on Telomere Length: A Systematic Review of Epidemiological Evidence and a Pilot Study during Pregnancy Full Text
*Childhood adversities are associated with shorter leukocyte telomere length at adult age in a population-based study Full Text
*The association between telomere length and ischemic stroke risk and phenotype Full Text

 

Odds & Sods
Feeling younger as a stress buffer: Subjective age moderates the effect of perceived stress on change in functional health
Metabolomic Changes are Predictive of Aging in Laying Hens
Rhesus monkeys as a translational model for late-onset Alzheimer's disease Full Text
*Factors contributing to cognitive improvement effects of acupuncture in patients with mild cognitive impairment: a pilot randomized controlled trial Full Text
Targeting conserved sequences circumvents the evolution of resistance in a viral gene drive against human cytomegalovirus
The marmoset as an important primate model for longitudinal studies of neurocognitive aging
*Functional brain changes associated with cognitive trajectories determine specific tDCS-induced effects among older adults
Deciphering the whale's secrets to have a long life
*Are the Acute Effects of THC Different in Aging Adults? Full Text
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