December 2019 Longevity Review

Posted by Chris Pollyanna , 06 January 2020 · 3,583 views

longevity review supplements gdf11 rapamycin intermittent fasting

Hello and welcome to 2019’s final monthly longevity review. Maybe it was the festive period, but things seemed a bit quieter on the longevity front the past month. The biggest flurry of activity appeared to be in quantifying ageing, be it in changes to the proteome, epigenome or metabolome amongst others; however, you’ll have to scroll down to the Ageing Clocks section to check that out. Of course there was the usual cavalcade of smaller studies, as the supplemental section will attest, but there were also a few studies worthy of making the round-up section.

If you were new to, or skeptical of, the longevity scene, then I hope that the demonstrable progress made this year would allay any fears that I’ve been talking utter bullsh*t. However, if these emails have been a bit too dense or overwhelming with all the links and such, then you’ll be glad to hear that I’m about to put together a (concise) review of the entire year, with only the most important advances mentioned. And if you’re still unconvinced, then the follow-up decade in review should slay any fears of the positive direction we are heading in. The advances have been astounding and leave me drooling at what is to come - hang on tight; it’s going to be quite the ride.

Happy New Decade! J

Follow me on Twitter @ChrisPollyanna1 for the latest updates (New Year’s resolution – at least a tweet a week!)

There's also a Toronto Local Facebook group which I hope you will join.

PS - any feedback is greatly appreciated.
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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.

December Round-Up:

GDF11 is a factor found in younger blood which declines with age and which has purported rejuvenatory effects, both in mice and in humans. Here, a form of gene therapy was used in mice livers to improve their metabolic health.

Gdf11 gene transfer prevents high fat diet-induced obesity and improves metabolic homeostasis in obese and STZ-induced diabetic mice Full Text

The two molecules used in this study, J147 & CMS121, are derivatives of Curcumin & Fisetin respectively. They had been developed to treat neurodegeneration, such as Alzheimer’s, but have shown broader anti-ageing effects. I had the pleasure of chatting to one of the lead researchers, Pamela Maher, at EARD 2019 in July, and she informed me that J147 had entered human trials earlier in 2019. (EDIT - As I was preparing my 2019 end of year review I noticed that this was one of my top results in my November newsletter as well! Whoops )

Alzheimer's drug candidates reverse broader aging, study shows Full Text

Alkahest is a company which has flown under the radar the last few years. It was formed by some of the leading scientists in parabiosis research, which is where the whole “young blood” fandango came from. They teamed up with one of the world’s leading blood product providers to conduct human trials using specific fractions of younger blood. Here they’ve advanced as far as Phase 2 in Alzheimer’s, with promising results. Larger trials are planned, including other indications, so this is a company worth keeping an eye on:

Alkahest Presents Data from Phase 2a Study in Mild-to-Moderate Alzheimer’s Disease

In this month’s Rapamycin news, there was another study in mice showing its heart beneficial effects, but the significance this time is that the beneficial effect lasted after its use was discontinued. And in a bonus study, there was a pre-print released of Rapamycin’s beneficial effect on oral health in mice as well.

Rapamycin persistently improves cardiac function in aged, male and female mice, even following cessation of treatment
Bonus study - Anti-Aging Drug Rejuvenates Oral Health

Not a drug this time, but a lifestyle intervention: intermittent fasting, which to my surprise was the number one diet related search term with Google this year. I’ve been practicing the time restricted eating form for the past five years, once the positive research started to emerge, and this study is yet more evidence in its favour.

Eating only during a 10-hour window improved health for those with metabolic syndrome Cool Video Overview
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Video to watch:
For your viewing pleasure, a bit of a blatant plug for the Life Expectancy Advocacy Foundation, whom I am now actively volunteering for. Apart from conference videos, scientific paper dissections and interviews, they have also now started to produce their own YouTube LifeXtenshow. Check it out:
https://www.youtube....uBwZwrsq83Nx2iq

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December 2019 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.
Mechanisms of Calorie Restriction: A Review of Genes Required for the Life-Extending and Tumor-Inhibiting Effects of Calorie Restriction. Full Text
Effects of Intermittent Fasting on Health, Aging, and Disease

Diet – let food be thy medicine…
The Mediterranean Diet Slows Down the Progression of Aging and Helps to Prevent the Onset of Frailty: A Narrative Review. Full Text
*Diet quality and cognitive function in mid-aged and older men and women Full Text
*Diet quality in late midlife is associated with faster walking speed in later life in women, but not men: findings from a prospective British birth cohort. Full Text

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*Amount and Intensity of Leisure-Time Physical Activity and Lower Cancer Risk Full Text
Genetic and Epigenetic Modulation of Cell Functions by Physical Exercise Full Text
*Lifelong Endurance Exercise as a Countermeasure Against Age-Related [Formula: see text] Decline: Physiological Overview and Insights from Masters Athletes.
*Aerobic Exercise Training Improves Cerebral Blood Flow and Executive Function: A Randomized, Controlled Cross-Over Trial in Sedentary Older Men. Full Text
*Skeletal Muscle Size, Function, and Adiposity with Lifelong Aerobic Exercise

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 carotinoid, it has anti-oxidative, anti-inflamatory, anti-cancer, neuro-protective and skin-protective qualities. I take 4 or 8 mg intermittently.
*Astaxanthin: How much is too much? A safety review.

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 bio-availability.
Curcumin ameliorates oxidative stress-induced intestinal barrier injury and mitochondrial damage by promoting Parkin dependent mitophagy through AMPK-TFEB signal pathway.
*The effect of curcumin supplementation on clinical outcomes and inflammatory markers in patients with ulcerative colitis
*The effects of curcumin supplementation on body mass index, body weight, and waist circumference in patients with nonalcoholic fatty liver disease: A systematic review and dose-response meta-analysis of randomized controlled trials.
*Antidiabetic Properties of Curcumin II: Evidence from In Vivo Studies. Full Text
Synergistic antioxidant effects of resveratrol and curcumin against fipronil-triggered oxidative damage in male albino rats.

Fisetin – a flavonoid found in highest concentration in strawberries. Senolytic, anti-inflammatory, anti-cancer, neuro-protective & Sirt1 activator. I take 100mg intermittently and will soon be trying a high dose senolytic n=1 trial.
Expression of Concern: Fisetin rescues retinal functions by suppressing inflammatory response in a DBA/2J mouse model of glaucoma

Nicotinamide MonoNucleotide (NMN) – newer NAD+ precursor. I take 250 – 500mg on days I exercise.
NAD+ precursor modulates post-ischemic mitochondrial fragmentation and reactive oxygen species generation via SIRT3 dependent mechanisms.
Nicotinamide mononucleotide ameliorates the depression-like behaviors and is associated with attenuating the disruption of mitochondrial bioenergetics in depressed mice.

Nicotinamide Riboside (NR) – NAD+ precursor.
*Nicotinamide riboside supplementation to improve skeletal muscle mitochondrial health and whole-body glucose homeostasis: does it actually work in humans?Does nicotinamide riboside supplementation improve muscle mitochondria?
Nicotinamide riboside alleviates alcohol-induced depression-like behaviours in C57BL/6J mice by altering the intestinal microbiota associated with microglial activation and BDNF expression.

Pterostilbene – found in blueberries. Anti-oxidant, anti-inflamatory 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 Attenuates Fructose-Induced Myocardial Fibrosis by Inhibiting ROS-Driven Pitx2c/miR-15b Pathway Full Text
Pterostilbene reduces endothelial cell injury in vascular arterial walls by regulating the Nrf2-mediated AMPK/STAT3 pathway in an atherosclerosis rat model Full Text
Dietary pterostilbene supplementation attenuates intestinal damage and immunological stress of broiler chickens challenged with lipopolysaccharide1.
Synergistic Action of Stilbenes in Muscadine Grape Berry Extract Shows Better Cytotoxic Potential Against Cancer Cells Than Resveratrol Alone. Full Text
Pterostilbene supplements carry the risk of drug interaction via inhibition of UDP-glucuronosyltransferases (UGT) 1A9 enzymes.

Resveratrol – found in the skin of grapes. Anti-oxidant, anti-inflamatory and Sir1 activator. Taking 250mg intermittently in the same pill as pterstilbene. Works better in conjunction with NAD+ precursors & Spermidine.
*Higher dose of resveratrol elevated cardiovascular disease risk biomarker levels in overweight older adults - A pilot study. As with most things, too much of a good thing can turn out to be bad. Here, high doses 1000mg per day appears to be negative.
Resveratrol ameliorates rheumatoid arthritis via activation of SIRT1-Nrf2 signaling pathway.
Protective effect of resveratrol on obesity-related osteoarthritis via alleviating JAK2/STAT3 signaling pathway is independent of SOCS3.
The Potential Use of Resveratrol for Cancer Prevention Full Text
Resveratrol delays postovulatory aging of mouse oocytes through activating mitophagy. Full Text
Exploring the Pharmacological Mechanism of Quercetin-Resveratrol Combination for Polycystic Ovary Syndrome: A Systematic Pharmacological Strategy-Based Research Full Text
Dose-Related Effects Of Resveratrol In Different Models Of Pulmonary Arterial Hypertension: Systematic Review.