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April 2021 Longevity Review

Posted by Chris Pollyanna , 10 May 2021 · 915 views

supplements nmn resveratrol spermidine health rejuvenation rapamycin metformin curcumin

Hello and welcome again to this month’s longevity review. Apart from the usual advances in longevity, I am excited to announce the imminent launch of what I think is the most important longevity crowdfunding campaign EVER. The Participatory Evaluation of Aging with Rapamycin for Longevity (PEARL) study will be the first trial to look at Rapamycin in humans in the context of longevity. As you know, Rapamycin is my favourite current longevity drug, as it has the most robust evidence that it works in animals - however, we need evidence that it works in humans as well, and this study will hopefully provide it. As of writing, the campaign should launch on May 17th. If there is any money you can possibly spare, please consider donating it to this noble cause. I cannot emphasise enough how important this is.


As to my own initiative - the launching of a Canadian Longevity Association, I’m still in the midst of gathering information & volunteers, but the first very basic iteration of the website is now up and running. It mainly consists of our aims, mission & contact info. I would love your thoughts and feedback! (Also, if there are any graphic designers out there - we need a unique logo :) )


A reminder that you can show your support via my Patreon account, which includes bonus material for members.


Follow me on Twitter @ChrisPollyanna1 for the latest updates.


And please also join my longevity Facebook group.




Starting off with an exciting paper showing how a combination of lifestyle changes could reduce epigenetic age by almost 2 years over the course of eight weeks! The lifestyle changes are readily achievable, and it is well worth reading the (short) full paper.
*Diet, Exercise Reduce Epigenetic Age in Human Clinical Trial Full Text


Nicotinamide Mononucleotide is a popular NAD+ precursor, but until now there hadn’t been any human efficacy studies. This first one didn’t have earth shattering results, but pointed towards some benefit and I eagerly await the results of other ongoing trials.
*NMN Human Trial Suggests Improved Muscle Glucose Metabolism Abstract
Hot off the press opinion from Peter Attia


Always good to see more results from my favourite longevity hack - Spermidine, which can be readily had from your diet (in my case I have some wheat germ every day). This is only an association study in humans, but I’ll take it!
*Spermidine for Cognitive Function in Flies, Mice, and Humans Full Text


CRISPR gene editing has revolutionised the genetic field since its discovery, and now it has been adapted to precisely edit the epigenetic marks which turn genes on and off. Could this be the start of a new revolution? Epigenetics is one of the most exciting areas in longevity, and this could potentially be a new way to reprogram the epigenome.
New CRISPR Technology Allows Turning Genes Off and On Again Abstract


Finally, to show that wishing to stop ageing and be able to regenerate is not pie in the sky thinking, nature has found ways to do it already, as these latest examples demonstrate:
No Sign of Aging in Long-Lived Bigmouth Buffalo Fish Full Text
'Astonishing': Scientists discover animal you can cut into three pieces, and every piece will regrow into a new animal Full Text


Covid-19 Longevity Related Papers:
Mesenchymal Stem Cells for the Compassionate Treatment of Severe Acute Respiratory Distress Syndrome Due to COVID 19 Full Text
Promising role of curcumin against viral diseases emphasizing COVID-19 management: A review on the mechanistic insights with reference to host-pathogen interaction and immunomodulation Full Text
Resveratrol-zinc nanoparticles or pterostilbene-zinc: Potential COVID-19 mono and adjuvant therapy Full Text


Videos to watch:
I wanted to point out a great YouTube channel by Micheal Lustgarten, who is trying to optimise his biomarkers for longevity using primarily dietary methods. This is especially useful information for understanding your blood test results and how your diet might relate to them.


Michael Lustgarten, Ph.D.

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 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.*
*Promoting Successful Cognitive Aging: A Ten-Year Update Full Text
*Lifestyle as determinant of all-cause mortality and age at death. A middle-aged male population followed-up 60 years until the survivors were aged 100 years


Fasting/Dietary Restriction
*Remodeling of the gut microbiome during Ramadan-associated intermittent fasting Full Text
Chrono-Nutrition Has Potential in Preventing Age-Related Muscle Loss and Dysfunction Full Text


*Associations of Dairy Intake with Circulating Biomarkers of Inflammation, Insulin Response, and Dyslipidemia among Postmenopausal Women
*Functional Frailty, Dietary Intake, and Risk of Malnutrition. Are Nutrients Involved in Muscle Synthesis the Key for Frailty Prevention? Full Text
*Seafood Intake as a Method of Non-Communicable Diseases (NCD) Prevention in Adults Full Text


*Qigong Attenuates Age-Related Cognitive Decline in Trial Full Text
*Effects of a 6 Week Low-Dose Combined Resistance and Endurance Training on T Cells and Systemic Inflammation in the Elderly Full Text
*Benefits of Resistance Training in Early and Late Stages of Frailty and Sarcopenia: A Systematic Review and Meta-Analysis of Randomized Controlled Studies Full Text
*Regular Exercise May Restore Certain Age-Related Alterations of Adaptive Immunity and Rebalance Immune Regulation Full Text
*Interval training versus moderate-intensity continuous training for cardiorespiratory fitness improvements in middle-aged and older adults: a systematic review and meta-analysis


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.


Molecular Mechanisms of Astaxanthin as a Potential Neurotherapeutic Agent Full Text
The effects of astaxanthin treatment on a rat model of Alzheimer's disease Full Text
Analysis of astaxanthin molecular targets based on network pharmacological strategies


*Pharmacokinetics of a Single Dose of Turmeric Curcuminoids Depends on Formulation: Results of a Human Crossover Study Full Text
*Curcumin and Its Modified Formulations on Inflammatory Bowel Disease (IBD): The Story So Far and Future Outlook Full Text
*Effect of curcumin on proinflammatory cytokines: A meta-analysis of randomized controlled trials


Fisetin inhibits lipopolysaccharide-induced inflammatory response by activating β-catenin, leading to a decrease in endotoxic shock Full Text
Flavonoid fisetin reverses impaired hippocampal synaptic plasticity and cognitive function by regulating the function of AMPARs in a male rat model of schizophrenia


*Effects of Melatonin Supplementation on Serum Oxidative Stress Markers and Disease Activity in Systemic Lupus Erythematosus Patients: A Randomized, Double-Blind, Placebo-Controlled Trial
Melatonin as a Potential Multitherapeutic Agent Full Text
Melatonin attenuates smoking-induced atherosclerosis by activating the Nrf2 pathway via NLRP3 inflammasomes in endothelial cells Full Text


Nicotinamide MonoNucleotide (NMN)
Pre-emptive Short-term Nicotinamide Mononucleotide Treatment in a Mouse Model of Diabetic Nephropathy
Nicotinamide mononucleotide production by fructophilic lactic acid bacteria Full Text


Nicotinamide Riboside (NR)
A decrease in NAD + contributes to the loss of osteoprogenitors and bone mass with aging Full Text
NAD + Repletion Reverses Heart Failure with Preserved Ejection Fraction
Inhibition of CD38 and supplementation of nicotinamide riboside ameliorate lipopolysaccharide-induced microglial and astrocytic neuroinflammation by increasing NAD


Pterostilbene, a Dimethylether Analogue of Resveratrol, Possesses High Potency in the Prevention of Platelet Activation in Humans and the Reduction of Vascular Thrombosis in Mice
Pterostilbene prevents methylglyoxal-induced cytotoxicity in endothelial cells by regulating glyoxalase, oxidative stress and apoptosis
Pterostilbene modifies triglyceride metabolism in hepatic steatosis induced by high-fat high-fructose feeding: a comparison with its analog resveratrol


*The Role of Resveratrol Administration in Human Obesity Full Text
An Exercise Mimetic Approach to Reduce Poststroke Deconditioning and Enhance Stroke Recovery Full Text
Resveratrol Prevents Campylobacter jejuni-Induced Leaky gut by Restoring Occludin and Claudin-5 in the Paracellular Leak Pathway Full Text


eIF5A hypusination, boosted by dietary spermidine, protects from premature brain aging and mitochondrial dysfunction Full Text
Spermidine at supraphysiological doses induces oxidative stress and granulosa cell apoptosis in mouse ovaries


Other available supplements
*A novel oral nutritional supplement improves gait speed and mitochondrial functioning compared to standard care in older adults with (or at risk of) undernutrition: results from a randomized controlled trial Full Text
*Dietary creatine and cognitive function in U.S. adults aged 60 years and over
*Sex-specific 25-hydroxyvitamin D threshold concentrations for functional outcomes in older adults: PRoject on Optimal VItamin D in Older adults (PROVIDO)
*Efficacy of various prescribed vitamin D supplementation regimens on 25-hydroxyvitamin D serum levels in long-term care Full Text
*Omega-3 supplementation and stress reactivity of cellular aging biomarkers: an ancillary substudy of a randomized, controlled trial in midlife adults
Microbial Metabolite Sodium Butyrate Attenuates Cartilage Degradation by Restoring Impaired Autophagy and Autophagic Flux in Osteoarthritis Development Full Text


Combinations of Supplements
*The effect of curcumin and zinc co-supplementation on glycemic parameters in overweight or obese prediabetic subjects: A phase 2 randomized, placebo-controlled trial with a multi-arm, parallel-group design
Nicotinamide mononucleotide and melatonin counteract myocardial ischemia-reperfusion injury by activating SIRT3/FOXO1 and reducing apoptosis in aged male rats
Dose-Related Urinary Metabolic Alterations of a Combination of Quercetin and Resveratrol-Treated High-Fat Diet Fed Rats Full Text
Prevention of Vascular Calcification by Magnesium and Selected Polyphenols Full Text


Prescription Supplements


Metformin: A Potential Candidate for Targeting Aging Mechanisms Full Text
Pretreatment with metformin protects mice from whole-body irradiation Full Text
Physiologically based metformin pharmacokinetics model of mice and scale-up to humans for the estimation of concentrations in various tissues Full Text


Rapamycin (sirolimus)
Rapamycin Added to Diet in Late Mid-Life Delays Age-Related Hearing Loss in UMHET4 Mice Full Text
Rapamycin restores brain vasculature, metabolism, and blood-brain barrier in an inflammaging model
mTOR attenuation with rapamycin reverses neurovascular uncoupling and memory deficits in mice modeling Alzheimer's disease


Other Areas of Interest (in alphabetical order)


Ageing Clocks & other biomarkers of ageing
*Clinical biomarkers and associations with healthspan and lifespan: Evidence from observational and genetic data Full Text
*VOCs profile can discriminate biological age Full Text
*Skeletal muscle transcriptome in healthy aging Full Text


Epigenetics & Cellular Reprogramming
Reprogramming: Emerging Strategies to Rejuvenate Aging Cells and Tissues Full Text
*A systematic review of biological, social and environmental factors associated with epigenetic clock acceleration Full Text
A ride through the epigenetic landscape: aging reversal by reprogramming Full Text


Exosomes (small packets of information released by cells)
HucMSC exosome-delivered 14-3-3ζ alleviates ultraviolet radiation-induced photodamage via SIRT1 pathway modulation Full Text
Quantitative proteomic analysis of extracellular vesicle subgroups isolated by an optimized method combining polymer-based precipitation and size exclusion chromatography Full Text


Genetics including CRISPR
*An integrative analysis of the age-associated multi-omic landscape across cancers Full Text
Comparative analyses of aging-related genes in long-lived mammals provide insights into natural longevity Full Text
Aging signatures across diverse tissue cells in mice Full Text


Lifespan Lengthening Interventions
Adiponectin preserves metabolic fitness during aging Full Text
Comparative Studies of Orthovanadate Nanoparticles and Metformin on Life Quality and Survival of Senile Wistar Rats Full Text
Ferulic Acid Supplementation Increases Lifespan and Stress Resistance via Insulin/IGF-1 Signaling Pathway in C. elegans Full Text
Rhodiola extract promotes longevity and stress resistance of Caenorhabditis elegans via DAF-16 and SKN-1
Trilobatin, a Component from Lithocarpus polystachyrus Rehd., Increases Longevity in C. elegans Through Activating SKN1/SIRT3/DAF16 Signaling Pathway Full Text


The aging gut microbiome and its impact on host immunity Full Text
Diet-Derived Antioxidants and Their Role in Inflammation, Obesity and Gut Microbiota Modulation Full Text
A Narrative Review of Gut-Muscle Axis and Sarcopenia: The Potential Role of Gut Microbiota Full Text


Miscellaneous Molecules (in alphabetical order)
Calcium Dobesilate Reverses Cognitive Deficits and Anxiety-Like Behaviors in the D-Galactose-Induced Aging Mouse Model through Modulation of Oxidative Stress Full Text
The Caveolin-1 Scaffolding Domain Peptide Reverses Aging-Associated Deleterious Changes in Multiple Organs Full Text
The Mechanisms and Functions of GDF-5 in Intervertebral Disc Degeneration Full Text
LCZ696 ameliorates lipopolysaccharide-induced endothelial injury Full Text
*Longitudinal Relationship Between Growth Differentiation Factor 11 and Physical Activity in Chronic Obstructive Pulmonary Disease Full Text
Growth differentiation factor 11: a "rejuvenation factor" involved in regulation of age-related diseases? Full Text
FDA-Approved Drug Is a Candidate for Dry AMD Treatment Full Text
Peripheral Administration of a Cell-Penetrating MOTS-c Analogue Enhances Memory and Attenuates Aβ 1-42- or LPS-Induced Memory Impairment through Inhibiting Neuroinflammation
Reduced Nicotinamide Mononucleotide (NMNH) Potently Enhances NAD + and Suppresses Glycolysis, the TCA Cycle, and Cell Growth
Integrated metabolomics and transcriptomics reveal the anti-aging effect of melanin from Sepiella maindroni ink (MSMI) on D-galactose-induced aging mice Full Text
SGLT2 inhibitors as calorie restriction-mimetics: insights on longevity pathways and age-related diseases


Observational Studies
*Association of sleep duration in middle and old age with incidence of dementia Full Text
*Mental Health and Religiosity in the Sardinian Blue Zone: Life Satisfaction and Optimism for Aging Well Full Text
*Determinants of Processing Speed Trajectories among Middle Aged or Older Adults, and Their Association with Chronic Illnesses: The English Longitudinal Study of Aging Full Text


50 years of the "war on cancer": lessons for public health and geroscience Full Text
No Time to Age: Uncoupling Aging from Chronological Time Full Text
The Zugzwang Hypothesis: Why Human Lifespan Cannot Be Increased Full Text


Other Ageing Biology
B-cell Depletion Ameliorates Alzheimer’s in Mice Full Text
Drug Allows Healing Without Scars in Mice Abstract


Effects of Transcranial Direct Current Stimulation Combined With Physical Training on the Excitability of the Motor Cortex, Physical Performance, and Motor Learning: A Systematic Review Full Text
The aging brain: sleep,the circadian clock and exercise Full Text
A Comprehensive Analysis into the Therapeutic Application of Natural Products as SIRT6 Modulators in Alzheimer's Disease, Aging, Cancer, Inflammation, and Diabetes Full Text


Senolytics/Senescent Cells
Senescence in tissue samples of humans with age-related diseases: a systematic review Full Text
Hypoxia Reduces SASP Without Reducing Senescent Cell Burden Full Text
The first non-invasive biomarker to track and verify efficacy of senolytic drugs Abstract


Skin & Beauty
*The Use of a Light-Emitting Diode Device for Neck Rejuvenation and Its Safety on Thyroid Glands Full Text
Daily photoprotection to prevent photoaging Full Text
Sirtuin 1 and Skin: Implications in Intrinsic and Extrinsic Aging-A Systematic Review Full Text


Stem Cells
*Cell-Based Therapies for Heart Failure Full Text
[size=4][font=arial]Stem cell therapy promotes recovery from stroke and dementia in mice [url="https://stm.sciencemag.org/content/13/590/eaaz6747"][color=rgb(17

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