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July 2021 Longevity Review

Posted by Chris Pollyanna , 13 August 2021 · 1,716 views

supplements stem cells microbiome nmn resveratrol rapamycin metformin fasting

Another month, another month of progress towards defeating the curse of ageing. This month’s Round-Up has a focus on human trial results, including promising trials with senolytics and NMN - though of course they are just scratching the surface of the latest developments, more of which can be found in the rest of this newsletter.
The big news from me last month was that I overtook the updating of lifespan.io’s Rejuvenation Roadmap, which charts the progress in developing longevity treatments. Take a look if you want to be heartened by how many companies are working on longevity and how close some treatments are to becoming commercially available.

For further glimpses of progress, next week (19-22 August), Lifespan.io will be hosting their annual conference, Ending Age Related Diseases 2021, virtually again. The program once more features a stellar lineup of the leading researchers in the field. If you want to hear about the latest breaking results before they’ve even had the chance to be published, then this is the place to be. Even better, you can grab yourself a free ticket to see the 4 keynote speakers. I will again be volunteering behind the scenes.

Now that in Toronto at least most people are fully vaccinated, I’m bringing my longevity Meetup group out of hibernation - I’m very much looking forward to finally seeing people in person again, and meeting some people for the first time. If you are free on Sunday evening, please feel free to join us!

Follow me on Twitter @ChrisPollyanna1 for the latest updates.

For previous updates, you can find them in the Canadian Longevity Association Facebook group, and also my Patreon account, which includes bonus material for members.
Finally, if you are interested in helping me create a Canadian longevity non-profit, then please contact me via the Canadian Longevity Association website.
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Round-Up:

As regular readers are well aware, senolytics hold great promise, but can that promise translate to humans? Here we have the first results from Unity’s second senolytic, this time for diabetic macular edema and wet age-related macular degeneration. Their first drug failed in Phase 2, so we have our fingers crossed that their second drug is more successful.
*Senolytics Show Positive Results in Phase 1 Clinical Trial Press Release

Not as powerful as senolytics, Nicotinamide Mononucleotide also shows promise based on animal data, but before this year there had been limited data in humans. Here we have the second human study to be released this year, once again showing some benefit, though perhaps not as great as we had hoped for.
*NMN Enhances Aerobic Capacity in Amateur Runners Full Text

The importance of our microbiome has increasingly become apparent, opening up opportunities for its modulation to improve our health. Here are a couple examples from the last month showing improvements in functional performance for the frail and metabolic biomarkers in the obese.
*Lactobacillus plantarum TWK10 Improves Muscle Mass and Functional Performance in Frail Older Adults: A Randomized, Double-Blind Clinical Trial Full Text
*Synbiotic Supplementation Improves Obesity Index and Metabolic Biomarkers in Thai Obese Adults: A Randomized Clinical Trial Full Text

Here, researchers have created stem cells which have been engineered to evade our immune system, thereby greatly extending their potential, as immune rejection was one of the limiting factors for their long-term use.
Engineered cells successfully treat cardiovascular and pulmonary disease Full Text

Covid-19 Longevity Related Papers:
Targeting aging cells improves survival Full Text
*Therapeutic prevention of COVID-19 in elderly: a case–control study Full Text
*The effect of metformin on mortality and severity in COVID-19 patients with diabetes mellitus Full Text
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Podcast to listen to:

Following on from my work on the Rejuvenation Roadmap, if you’re interested in finding out more about the biotech side of longevity, then my friend and fellow Torontonian’s podcast is well worth checking out. The Longevity Biotech Show features in depth interviews with the founders and leading lights from biotechs interested in longevity.

The Longevity Biotech Show

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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 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.
Fasting: How to Guide Full Text
Dietary Restriction for Kidney Protection: Decline in Nephroprotective Mechanisms During Aging Full Text
Effects of fasting on skeletal muscles and body fat of adult and old C57BL/6J mice

Diet – let food be thy medicine…
*Higher levels of omega-3 acids in the blood increases life expectancy by almost five years Full Text
*A fermented-food diet increases microbiome diversity and lowers inflammation, study finds Abstract
*Eating whole grains linked to smaller increases in waist size, blood pressure, blood sugar Full Text

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*Six weeks of high intensity cycle training reduces H2O2 emission and increases antioxidant protein levels in obese adults with risk factors for type 2 diabetes Full Text
*High-Intensity Interval Training in Older Adults: a Scoping Review Full Text
*Regular Strength and Sprint Training Counteracts Bone Aging: A 10-Year Follow-Up in Male Masters Athletes 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.
Mitochondrion as a Target of Astaxanthin Therapy in Heart Failure Full Text
Astaxanthin Protects Human Granulosa Cells against Oxidative Stress through Activation of NRF2/ARE Pathway and Its Downstream Phase II Enzymes Full Text
Ameliorative effects of astaxanthin against copper(II) ion-induced alteration of pentose phosphate pathway and antioxidant system enzymes in rats

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.
Tetrahydrocurcumin ameliorates Alzheimer's pathological phenotypes by inhibition of microglial cell cycle arrest and apoptosis via Ras/ERK signaling Full Text
Curcumin as a Natural Remedy for Atherosclerosis: A Pharmacological Review Full Text
Is Curcumin the Answer to Future Chemotherapy Cocktail? 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 Ameliorates the Inflammation and Oxidative Stress in Lipopolysaccharide-Induced Endometritis Full Text
Fisetin promotes osteoblast differentiation and osteogenesis through GSK-3β phosphorylation at Ser9 and consequent β-catenin activation, inhibiting osteoporosis
Ameliorative effects of fisetin in letrozole-induced rat model of polycystic ovary syndrome

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.
Research progress of melatonin (MT) in improving ovarian function: a review of the current status Full Text
Melatonin Attenuates Neuroinflammation by Down-Regulating NLRP3 Inflammasome via a SIRT1-Dependent Pathway in MPTP-Induced Models of Parkinson’s Disease Full Text
The mechanism of oral melatonin ameliorates intestinal and adipose lipid dysmetabolism through reducing Escherichia coli-derived lipopolysaccharide Full Text

Nicotinamide MonoNucleotide (NMN) – NAD+ precursor. I take 250 – 500mg on days I exercise.
Nicotinamide Mononucleotide Combined With Lactobacillus fermentum TKSN041 Reduces the Photoaging Damage in Murine Skin by Activating AMPK Signaling Pathway Full Text
*NAD+ metabolism and cardiometabolic health: the human evidence 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 pulmonary fibrosis by regulating ASIC2 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.
Effects and Mechanisms of Resveratrol on Aging and Age-Related Diseases Full Text
Prospective Pharmacological Potential of Resveratrol in Delaying Kidney Aging Full Text
*Effect of resveratrol on inflammatory cytokines: A meta-analysis of randomized controlled trials

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.
The metabolic role of spermidine in obesity: Evidence from cells to community

Other available supplements or natural substances (in alphabetical order)
Astragaloside IV prevents memory impairment in D-galactose-induced aging rats via the AGEs/RAGE/ NF-κB axis Full Text
*Impact of β-hydroxy-β-methylbutyrate (HMB) on muscle loss and protein metabolism in critically ill patients: A RCT
*Effect of Carnosine or β-Alanine Supplementation on Markers of Glycemic Control and Insulin Resistance in Humans and Animals: A Systematic Review and Meta-analysis Full Text
Matricaria chamomilla (Chamomile) Ameliorates Muscle Atrophy in Mice by Targeting Protein Catalytic Pathways, Myogenesis, and Mitochondrial Dysfunction
Folic Acid Inhibits Aging-Induced Telomere Attrition and Apoptosis in Astrocytes In Vivo and In Vitro
Grape Seed Proanthocyanidin Extract Moderated Retinal Pigment Epithelium Cellular Senescence Through NAMPT/SIRT1/NLRP3 Pathway Full Text
Grape skin extract modulates neuronal stem cell proliferation and improves spatial learning in senescence-accelerated prone 8 mice Full Text
*Clinical trial on the effects of oral magnesium supplementation in stable-phase COPD patients Full Text
*Non-steroidal Anti-inflammatory Drug Use and Risk of Age-Related Macular Degeneration in the California Teachers Study Full Text