June 2020 Longevity Review

Posted by Chris Pollyanna , 20 July 2020 · 2,281 views

longevity supplements covid19 senolytics stem cells nad+ resveratrol astaxanthin spermidine

June 2020 Longevity Review

Hello and welcome again to this month’s longevity review. I’ve put together this review in the sweltering Torontonian summer heat where we’ve already had more days over 30 degrees than the whole of last summer - not helped by my stubborn (or is it crazy?) refusal to succumb to A/C! Similarly, the longevity field continues to heat up, especially areas related to senolytics where two new methods involving the immune system have been published. Also in the round-up section, you will find news about stem cells, a healthspan lengthening peptide, more potential longevity compounds and another potential epigenetic age reverser.

In the supplemental section, after being unable to fully upload last month’s review due to size restrictions, I’ve decided to limit each topic to only three entries (with exceptions). I think it had become a bit bloated and hopefully with greater selectivity it will be more pertinent and useful to you - let me know in the comments what you think.

A reminder that next month sees the return of the premier longevity conference Ending Age Related Diseases 2020 on 20-21 August. Although it has been forced to move online, that does mean that you’ll be able to attend in your underwear! If you have any interest at all in witnessing the unveiling of cutting edge longevity research, then be sure not to miss this opportunity, especially as there is even a free option (& just saw before posting this that there’s a 10% discount until July 23rd).

Stay safe!

Follow me on Twitter @ChrisPollyanna1 for the latest updates.
And please join my longevity Facebook Group: the Toronto Longevity Association.
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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.

June Round-Up:

The introduction of CAR-T cell immunotherapy has been a revolution in the treatment of certain blood cancers, resulting in durable responses in formerly incurable indications. What if the same precise power could be used to eliminate senescent cells? Well, that is exactly what this new research has achieved:

Deploying Immunotherapy Against Senescent Cells

T cells engineered to target senescence

In the current hunt for a vaccine against COVID-19 it is interesting to note this study which utilises the same principle, but this time targeting senescent cells. It would be quite something if eventually we could get vaccinated against one of the main drivers of ageing.

A vaccine targeting aged cells mitigates metabolic disorders in obese mice Full Text

The consequences of an ageing immune system have been vividly highlighted by the current pandemic. The Thymus and Spleen are components of the immune system which decline with age. Here, researchers have used stem cells to reverse the dysfunction of those organs in ageing rats.

Bone Marrow Mesenchymal Stem Cells Improve Thymus and Spleen Function of Aging Rats Through Affecting P21/PCNA and Suppressing Oxidative Stress Full Text

Humanin is a peptide produced by the mitochondria which declines with age and has been linked with health and lifespan. Here, elevating levels of this peptide lengthened the lifespans of worms and the health of mice.

Protein in mitochondria appears to regulate health and longevity Full Text

The quest to identify new potential longevity enhancing molecules continues, and in this example a Canadian group of researchers have been mining plants to discover extracts which increase the lifespan of yeast.

Discovery of Fifteen New Geroprotective Plant Extracts and Identification of Cellular Processes They Affect to Prolong the Chronological Lifespan of Budding Yeast Full Text

Finally, here is some intriguing news via a supplement company press release which claims possible epigenetic age reversal. Major caveats apply as this has not been peer reviewed, the epigenetic test was proprietary and they are a company trying to make money - however, larger trials are planned, there is at least one paper under peer review and the initial science comes from the reputable Buck Institute. Here is LEAF’s take:

Pilot Study Results Suggest Epigenetic Age Reversal

Covid-19 Longevity Related Papers:
COVID-19 and Crosstalk With the Hallmarks of Aging Full Text
Reversing immunosenescence for prevention of COVID-19 Full Text
From Causes of Aging to Death From COVID-19 Full Text
Potential Therapeutic Targets for Combating SARS-CoV-2: Drug Repurposing, Clinical Trials and Recent Advancements Full Text
Therapeutic Potential of Resveratrol Against Emerging Respiratory Viral Infections Full Text
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Video to watch:
The Life Extension Advocacy Foundation have just launched a regular news show called Lifespan News dedicated to bringing you the very latest reports from the longevity field. Check out the inaugural episode:
Lifespan News Episode 1
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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)

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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.
*Metabolic Effects of Late Dinner in Healthy Volunteers - A Randomized Crossover Clinical Trial

Diet – let food be thy medicine…
*Light drinking may protect brain function Full Text
*Meta-analysis of the Association Between Nut Consumption and the Risks of Cancer Incidence and Cancer-Specific Mortality Full Text
*Supplementation With Whey Protein, Omega-3 Fatty Acids and Polyphenols Combined With Electrical Muscle Stimulation Increases Muscle Strength in Elderly Adults With Limited Mobility: A Randomized Controlled Trial Full Text

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*Exercise Interventions for Older Adults: A Systematic Review of Meta-Analyses Full Text
*Systematic Review of the Prospective Association of Daily Step Counts With Risk of Mortality, Cardiovascular Disease, and Dysglycemia Full Text
*Sedentary and Trained Older Men Have Distinct Circulating Exosomal microRNA Profiles at Baseline and in Response to Acute Exercise 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 3-Month Astaxanthin Supplementation on Cardiac Function in Heart Failure Patients With Left Ventricular Systolic Dysfunction-A Pilot Study Full Text
Effect of Astaxanthin on Activation of Autophagy and Inhibition of Apoptosis in Helicobacter pylori-Infected Gastric Epithelial Cell Line AGS Full Text
Safety Assessment of Astaxanthin From Haematococcus Pluvialis: Acute Toxicity, Genotoxicity, Distribution and Repeat-Dose Toxicity Studies in Gestation 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 bioavailability.
*Further Evidence of Benefits to Mood and Working Memory From Lipidated Curcumin in Healthy Older People: A 12-Week, Double-Blind, Placebo-Controlled, Partial Replication Study Full Text
*A Pilot Study of the Effect of Curcumin on Epigenetic Changes and DNA Damage Among Patients With Non-Alcoholic Fatty Liver Disease: A Randomized, Double-Blind, Placebo-Controlled, Clinical Trial
*Significant Immunomodulatory Properties of Curcumin in Patients With Osteoarthritis; A Successful Clinical Trial in Iran

Fisetin – a flavonoid found in highest concentration in strawberries. Senolytic, anti-inflammatory, anti-cancer, neuro-protective & Sirt1 activator. I take 100mg intermittently.
Fisetin Prevents the Aging-Associated Decline in Relative Spectral Power of α, β and Linked MUA in the Cortex and Behavioral Alterations

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.
Melatonin: An Endogenous Miraculous Indolamine, Fights Against Cancer Progression
Melatonin Regulates Mitochondrial Dynamics and Alleviates Neuron Damage in Prion Diseases Full Text

Nicotinamide Riboside (NR) – NAD+ precursor.
Nicotinamide Riboside Supplementation Corrects Deficits in Oxytocin, Sociability and Anxiety of CD157 Mutants in a Mouse Model of Autism Spectrum Disorder Full Text
Implications of NAD + Boosters in Translational Medicine 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.
Pterostilbene Alleviates Cerebral Ischemia and Reperfusion Injury in Rats by Modulating Microglial Activation
Comparison of the Protective Effects of Resveratrol and Pterostilbene Against Intestinal Damage and Redox Imbalance in Weanling Piglets Full Text
Induction of Autophagy by Pterostilbene Contributes to the Prevention of Renal Fibrosis via Attenuating NLRP3 Inflammasome Activation and Epithelial-Mesenchymal Transition 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.
*Regular Supplementation With Resveratrol Improves Bone Mineral Density in Postmenopausal Women: A Randomised, Placebo-Controlled Trial Full Text
*No Effect of Resveratrol Supplementation After 6 Months on Insulin Sensitivity in Overweight Adults: A Randomized Trial Full Text
*Oral Resveratrol Supplementation Improves Metabolic Syndrome Features in Obese Patients Submitted to a Lifestyle-Changing Program

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.
*Spermine and Spermidine Modulate T-cell Function in Older Adults With and Without Cognitive Decline Ex Vivo Full Text
Spermidine Supplementation and Voluntary Activity Differentially Affect Obesity-Related Structural Changes in the Mouse Lung

Other available supplements & combinations
CD38 Inhibition by Apigenin Ameliorates Mitochondrial Oxidative Stress Through Restoration of the Intracellular NAD +/NADH Ratio and Sirt3 Activity in Renal Tubular Cells in Diabetic Rats Full Text
Vitamin D Deficiency as a Potential Risk Factor for Accelerated Aging, Impaired Hippocampal Neurogenesis and Cognitive Decline: A Role for Wnt/β-catenin Signaling Full Text
Effect of Daily 2000 IU Versus 800 IU Vitamin D on Blood Pressure Among Adults Age 60 Years and Older: A Randomized Clinical Trial
L-histidine and L-carnosine Exert Anti-Brain Aging Effects in D-galactose-induced Aged Neuronal Cells Full Text
Quercetin Attenuates Pancreatic and Renal D-Galactose-Induced Aging-Related Oxidative Alterations in Rats 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.
*Association of Pre-Stroke Metformin Use, Stroke Severity, and Thrombolysis Outcome
Combining a High Dose of Metformin With the SIRT1 Activator, SRT1720, Reduces Lifespan in Aged Mice Fed a High-Fat Diet Full Text
Transcriptomic Landscape Profiling of Metformin-Treated Healthy Mice: Implication for Potential Hypertension Risk When Prophylactically Used Full Text

Rapamycin (sirolimus) – first drug proven to increase the health & lifespan of mice. Currently used for organ transplantation and against cancer.
Improved Health-Related Quality of Life in Patients Treated With Topical Sirolimus for Facial Angiofibroma Associated With Tuberous Sclerosis Complex Full Text
Inhibition of mTORC1 Improves STZ-induced AD-like Impairments in Mice
Rapamycin-PLGA Microparticles Prevent Senescence, Sustain Cartilage Matrix Production Under Stress and Exhibit Prolonged Retention in Mouse Joints

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:
A Comparison of Epigenetic Mitotic-Like Clocks for Cancer Risk Prediction Full Text
New Targeted Approaches for Epigenetic Age Predictions Full Text
Modelling Biological Age Based on Plasma Peptides in Han Chinese Adults Full Text

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:
Generation of Inner Ear Hair Cells by Direct Lineage Conversion of Primary Somatic Cells
A simpler way to make sensory hearing cells Full Text
Inhibition of Neural Stem Cell Aging Through the Transient Induction of Reprogramming Factors
Parkinson’s Disease Symptoms Reversed in Mice

Microbiome – all the little critters living in and on us have a major influence on our health and potentially our longevity.
Reversing Atherosclerosis by Resetting Gut Bacteria
Gut Microbiota Remodeling Reverses Aging-Associated Inflammation and Dysregulation of Systemic Bile Acid Homeostasis in Mice Sex-Specifically Full Text
Association of Gut Microbiota Composition and Function With an Aged Rat Model of Senile Osteoporosis Using 16S rRNA and Metagenomic Sequencing Analysis Full Text

Senolytics – not 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:
Targeting Cardiac Stem Cell Senescence to Treat Cardiac Aging and Disease Full Text
Role of Immune Cells in the Removal of Deleterious Senescent Cells Full Text
Transient Metabolic Improvement in Obese Mice Treated With Navitoclax or dasatinib/quercetin 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.
*Beneficial Effects of Food Supplements Based on Hydrolyzed Collagen for Skin Care (Review) Full Text
Topical GDF11 Accelerates Skin Wound Healing in Both Type 1 and 2 Diabetic Mouse Models

Stem Cells & Exosomes (small packets of information released by cells)
Intravenous Bone Marrow Mononuclear Cells Transplantation in Aged Mice Increases Transcription of Glucose Transporter 1 and Na +/K +-ATPase at Hippocampus Followed by Restored Neurological Functions Full Text
Plasma Endothelial Cells-Derived Extracellular Vesicles Promote Wound Healing in Diabetes Through YAP and the PI3K/Akt/mTOR Pathway Full Text
Small Extracellular Vesicles Have GST Activity and Ameliorate Senescence-Related Tissue Damage 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 Is Inversely Associated With Arterial Wave Reflection in 566 Normotensive and Never-Treated Hypertensive Subjects Full Text
Physical Activity, a Modulator of Aging Through Effects on Telomere Biology Full Text
Reduced Telomere Shortening in Lifelong Trained Male Football Players Compared to Age-Matched Inactive Controls

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:
Influences of Circulatory Factors on Intervertebral Disc Aging Phenotype Full Text
AMBAR, an Encouraging Alzheimer's Trial That Raises Questions