July 2019 Longevity Review
longevity review supplements nad+ rapamycin senolytics
July Longevity Update
Hello and welcome once again to this month’s longevity update. I’ve just had the busiest summer ever teaching-wise. So busy, that I couldn’t even follow the latest longevity developments. Therefore it was quite novel, when I sat down to compile this update, to have almost no idea what transpired during July. Needless to say, a lot did, including a result I’ve been waiting for since David Sinclair sent some cryptic tweets last summer.
As mentioned in the last update, I volunteered at Ending Age-Related Diseases in New York, which was the highlight of my summer. It wasn’t so much finding out the latest news which made it great; it was the feeling of participation and meeting so many wonderful people. After having spent so much time communicating with other enthusiasts only via computer, it was refreshing to finally be surrounded by like-minded people. I highly recommend attending next year’s conference, or any other longevity related conference – a list of which can be found here. If you’re curious to read more about it, here’s the official write up & the view from Fight Aging!
Follow me on Twitter @ChrisPollyanna1 for the latest updates! (after a two month hiatus… )
Finally, any feedback is greatly appreciated… J
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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 have still 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.
July Round-Up:
- The cryptic tweets mentioned were about the promise of cellular reprogramming, whereby the age of a cell gets reverted back to youthfulness by the introduction of genetic factors. I strongly believe that this area is going to explode in the next few years and is the closest thing we have to a “silver bullet” against ageing. In the present study, which has not been peer reviewed yet, they were able to re-grow the optic nerve of mice – something hitherto impossible: Reversal of ageing- and injury-induced vision loss by Tet-dependent epigenetic reprogramming
- An interesting study where they took a gene associated with longevity among centenarians and gave it to a group of mice. This resulted in the mice having a reduction in the hardening of their arteries: Single systemic transfer of a human gene associated with exceptional longevity halts the progression of atherosclerosis and inflammation in ApoE knockout mice through a CXCR4-mediated mechanism. Full Text
- Telomeres, the protective caps at the end of our chromosomes, have been the subject of intense debate in the ageing community: is their length and reduction over time a symptom or a cause of ageing? So far the results have been inconclusive, but the following animal comparative study sheds some new light. It turns out that it is not the length of the telomere which predicts a species lifespan, it is the rate of shortening (of course this doesn’t tell us about cause and effect): Telomere shortening rate predicts species life span. Full Text LEAF Summary & an interview with the author, who was a headline speaker at the conference.
- It’s been just over 30 years since the modern field of ageing research started and the following review, from the leading lights of the field, provides an overview of the progress made so far, as well as arguing that we have now reached an inflection point whereby we can start to translate our understanding into treatments to increase human healthspan: From discoveries in ageing research to therapeutics for healthy ageing
- And finally, two articles about my favourite available longevity drug: Rapamycin. OK, the first article is not about Rapamycin – it’s about a similar drug, working on the same pathway, which is currently in human clinical trials. Rapamycin is now off-patent, so pharma can’t make big bucks off it, however, with this “new” drug, they can charge whatever they want! It is still significant though, for if it gains approval in a couple of years, it will be the first true anti-ageing drug on the market: Can a Single Pill Keep You Healthy to 100? For those unwilling to wait a few years to be charged an exorbitant fee, there is always generic Rapamycin, and the second article is about the men (the article is from Men’sHealth), who like me, have followed this second path: This Obscure, Potentially Dangerous Drug Could Stop Aging This is a surprisingly excellent article, featuring the same doctor I got a prescription from, as well as an honest assessment of the potential drawbacks and benefits.
Videos to watch:
No conference would be complete without an attendant videographer and Ending Age-Related Diseases was no exception. Only a few videos have been posted so far, but more will be added in the coming months:
YouTube Channel:
https://www.youtube....PYWUlg0vaKtO1Re
Facebook Channel:
https://www.facebook...18828314884987/
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Further sources of information:
Fight Aging!
Life Extension Advocacy Foundation (LEAF)
Longecity (good forums where the self-experimenters reside!)
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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July 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.
*2 years of calorie restriction and cardiometabolic risk (CALERIE): exploratory outcomes of a multicentre, phase 2, randomised controlled trial.
*Caloric restriction, longevity and aging: Recent contributions from human and non-human primate studies.
Diet – let food be thy medicine…
*A Vitamin D, Calcium and Leucine-Enriched Whey Protein Nutritional Supplement Improves Measures of Bone Health in Sarcopenic Non-Malnourished Older Adults: The PROVIDE Study. Full Text
*Prospective Associations of Diet Quality With Incident Frailty in Older Adults: The Health, Aging, and Body Composition Study. Full Text
*Acute Supplementation with Nitrate-Rich Beetroot Juice Causes a Greater Increase in Plasma Nitrite and Reduction in Blood Pressure of Older Compared to Younger Adults. Full Text
*Alcohol Consumption in Later Life and Mortality in the United States: Results from 9 Waves of the Health and Retirement Study.
*A Mediterranean Diet with Fresh, Lean Pork Improves Processing Speed and Mood: Cognitive Findings from the MedPork Randomised Controlled Trial. Full Text
*Is there a relationship between chocolate consumption and symptoms of depression? A cross-sectional survey of 13,626 US adults Full Text
Recent Research on the Health Benefits of Blueberries and Their Anthocyanins Full Text
Alcohol in the Aging Brain - The Interplay Between Alcohol Consumption, Cognitive Decline and the Cardiovascular System. Full Text
Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*Aerobic and resistance exercise training reverses age-dependent decline in NAD+ salvage capacity in human skeletal muscle. Full Text
*Chronic Fish Oil Consumption with Resistance Training Improves Grip Strength, Physical Function, and Blood Pressure in Community-Dwelling Older Adults. Full Text
*The Role of Muscle Mass Gain Following Protein Supplementation Plus Exercise Therapy in Older Adults with Sarcopenia and Frailty Risks: A Systematic Review and Meta-Regression Analysis of Randomized Trials. Full Text
Antiaging Effects of Aerobic Exercise on Systemic Arteries Full Text
The Impact of Different Types of Exercise Training on Peripheral Blood Brain-Derived Neurotrophic Factor Concentrations in Older Adults: A Meta-Analysis.
Non-prescription Supplements (in alphabetical order)
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 4mg daily.
*Effects of astaxanthin on VEGF level and antioxidation in human aqueous humor: difference by sex. Full Text
Do We Utilize Our Knowledge of the Skin Protective Effects of Carotenoids Enough? Full Text
The Neuroprotective Effects of Astaxanthin: Therapeutic Targets and Clinical Perspective. Full Text
Curcumin – the spice which gives curries their yellow colour. Anti-inflammatory and neuroprotective. I take 1 gram a day. Needs to be taken with black pepper (piperine) to improve bio-availability.
*Eight Weeks of a High Dose of Curcumin Supplementation May Attenuate Performance Decrements Following Muscle-Damaging Exercise. Full Text
*Curcumin and inflammation in non-alcoholic fatty liver disease: a randomized, placebo controlled clinical trial. Full Text
*Bio-optimized Curcuma longa extract is efficient on knee osteoarthritis pain: a double-blind multicenter randomized placebo controlled three-arm study. Full Text
*Food matrix and co-presence of turmeric compounds influence bioavailability of curcumin in healthy humans.
Does Turmeric/curcumin Supplementation Change Anthropometric Indices in Patients with Non-alcoholic Fatty Liver Disease? A Systematic Review and Meta-analysis of Randomized Controlled Trials Full Text
Is curcumin bioavailability a problem in humans: lessons from clinical trials.
Anti-inflammatory Action of Curcumin and Its Use in the Treatment of Lifestyle-related Diseases Full Text
Fisetin – a flavonoid found in highest concentration in strawberries. Senolytic, anti-inflammatory, anti-cancer, neuro-protective & Sirt1 activator. I take 100mg daily.
Nicotinamide MonoNucleotide (NMN) – newer NAD+ precursor. I take 250mg daily.
Nicotinamide Riboside (NR) – NAD+ precursor.
*Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults Full Text
Nicotinamide riboside promotes autolysosome clearance in preventing doxorubicin-induced cardiotoxicity.
Pterostilbene – found in blueberries. Anti-oxidant, anti-inflamatory and Sir1 activator. Similar to, but with greater bioavailability than resveratrol. Just started taking 50mg again daily. Works better in conjunction with NAD+ precursors.
Pterostilbene: Mechanisms of its action as oncostatic agent in cell models and in vivo studies.
Antidiabetic effects of pterostilbene through PI3K/Akt signal pathway in high fat diet and STZ-induced diabetic rats.
Prevention of Vascular Inflammation by Pterostilbene via Trimethylamine-N-Oxide Reduction and Mechanism of Microbiota Regulation
Resveratrol – found in the skin of grapes. Anti-oxidant, anti-inflamatory and Sir1 activator. Just started taking 250mg a day. Works better in conjunction with NAD+ precursors & Spermidine.
*The Effects of Resveratrol Supplementation on Endothelial Function and Blood Pressures Among Patients with Metabolic Syndrome and Related Disorders: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
*Effect of resveratrol on non-alcoholic fatty liver disease Full Text
*Health Benefits of Resveratrol in Kidney Disease: Evidence from In Vitro and In Vivo Studies. Full Text
*Resveratrol and cognitive decline: a clinician perspective. Full Text
Resveratrol alleviates chronic "real-world" ambient particulate matter-induced lung inflammation and fibrosis by inhibiting NLRP3 inflammasome activation in mice.
Resveratrol shifts energy metabolism to increase lipid oxidation in healthy old mice. Full Text
Spermidine – found in wheat germ and a potent inducer of autophagy, it works in synergy with Resveratrol. I try to eat a couple of tablespoons of wheat germ every day.
Spermidine Confers Liver Protection by Enhancing NRF2 Signaling Through a MAP1S-Mediated Noncanonical Mechanism.
The metabolomic signature of extreme longevity: naked mole rats versus mice. Full Text
Polyamines in Food Full Text
Prescription Supplements
Rapamycin (sirolimus) – first drug proven to increase the health & lifespan of mice. Currently used for organ transplantation and against cancer. Taking 5mg once a week.
*Oral and Topical Sirolimus for Vascular Anomalies: a Multicentre Study and Review. Full Text
*Sirolimus as a new drug to treat RIF patients with elevated Th17/Treg ratio: A double-blind, phase II randomized clinical trial.
Differential effects of rapamycin on glucose metabolism in 9 inbred strains.
Targeting mTOR for cancer therapy Full Text
Partial inhibition of mTORC1 in aged rats counteracts the decline in muscle mass and reverses molecular signaling associated with sarcopenia. Full Text
mTOR as a central regulator of lifespan and aging. Full Text
A novel rapamycin analog is highly selective for mTORC1 in vivo. Full Text
Lifespan extension drug interventions affect adipose tissue inflammation in aging.
Effect of caloric restriction and rapamycin on ovarian aging in mice
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:
Fibrates as drugs with senolytic and autophagic activity for osteoarthritis therapy Full Text
Stabilizing heterochromatin by DGCR8 alleviates senescence and osteoarthritis. Full Text
Increased renal cellular senescence in murine high-fat diet: effect of the senolytic drug quercetin
Cellular Senescence and the Kidney: Potential Therapeutic Targets and Tools. Full Text