December 2020 Longevity Review

Posted by Chris Pollyanna , 02 January 2021 · 1,562 views

supplements cellular reprogramming resveratrol nmn nad+ spermidine astaxanthin rapamycin

Hello and welcome to 2020’s final longevity review. As this dreadful year mercifully comes to a close, it has at least left us with a last few parting longevity gifts. In particular, this month saw the long awaited publication of a cellular reprogramming study which restored sight to blinded mice. The significance is that they actually turned back the epigenetic clock, making the cells youthful again, and therefore enabling the optic nerve to regrow. Hopefully the coming year will see a deluge of similar studies on other body parts and indeed whole animals.

Speaking of the coming year, I will soon have some news to share regarding forthcoming plans. In the meantime, I hope that everyone else shares my excitement for the promise of 2021 - may all your dreams and wishes be fulfilled.
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.se, 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.

Round-Up:

Excited that after more than a year of being out on preprint, this groundbreaking study has finally been published. In this study, researchers regrew the optic nerve of mice, restoring their vision, using epigenetic reprogramming. The regrowth of the optic nerve has never been achieved before, and here it was done by making the cells actually younger. Meanwhile, epigenetic reprogramming holds such potential that this study offers merely a tantalising glimpse of what that potential could be.
Reversing Cellular Age in Mice Restores Vision Nature Review Abstract

Just a safety trial, but with some interesting efficacy results, this study involved infusing a plasma fraction into patients to try to treat Alzheimer’s. Previous research has shown that adding young plasma to old animals has improved their cognition among other positive effects. Now, that research is transitioning to humans via Alkahest, the company behind this study. This longevity treatment has one of the shortest potential routes to general availability, so it is great to see human results start to emerge.
*Safety and tolerability of GRF6019 in mild-to-moderate Alzheimer's disease dementia Full Text

The removal of senescent cells with senolytics has been shown to be beneficial, but what if the cells could be reverted back to their pre-senescent state instead? Well, that is exactly what these researchers have accomplished. Using human skin cells, they successfully removed their senescent hallmarks, which resulted in restored skin regeneration capacity.
Simulations open a new way to reverse cell aging Abstract

The thymus has been a regular feature in the round-up due to the fact that if its atrophy could be reversed, then our immune systems might be improved as well. Here, researchers have regrown functional thymi in mice using decellularization, a promising process which could lead to other replacement organs being grown such as the heart or liver. This is one of the first times that a fully functioning organ has been produced in a living animal:
Decellularized, Functional Thymus Regeneration in Mice Full Text

In this study, researchers used a small molecule (ISRIB) to partially restore brain function in aging mice, with a single injection having long lasting effects. The rights to this molecule have been snapped up by CALICO, the company founded by Google to tackle longevity.
Aging Brain Function Partially Restored With Small Molecule Full Text

Here, the inhibition of a single enzyme (15-PGDH) resulted in increased muscle mass, strength and endurance in mice, which would be useful for the prevention of sarcopenia.
Blocking protein restores strength, endurance in old mice Abstract

Since it is the season of giving, here is an extra bonus news nugget, but one which should be treated with extreme caution. Back in May, I reported on a paper where the mere dilution of blood plasma resulted in some rejuvenatory effects. Those results were in mice, and while the same researchers are planning a human trial, a couple of Russian Biohackers beat them to it with intriguing results.
Biohackers Perform First Plasma Dilution Experiment on Humans

Covid-19 Longevity Related Papers:

Possible Prophylactic Approach for SARS-CoV-2 Infection by Combination of Melatonin, Vitamin C and Zinc in Animals Full Text
Resveratrol, Rapamycin and Metformin as Modulators of Antiviral Pathways Full Text
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Video to watch:
Here is LEAF’s Journal Club review of this month’s lead Round-Up item, including the study author as a special guest. Unfortunately, only on Facebook at the moment.
Journal Club – Reversing Cellular Age in Mice Restores Vision
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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)
Aging Matters (good blog from the programmed ageing side)

Research Institutes:
SENS Research Foundation
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

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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 a healthy 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.
Still Living Better through Chemistry: An Update on Caloric Restriction and Caloric Restriction Mimetics as Tools to Promote Health and Lifespan Full Text
Regulation of glucose homeostasis by calorie restriction and periodic fasting Full Text

Diet – let food be thy medicine…
*Diet modifications -- including more wine and cheese -- may help reduce cognitive decline, study suggests Abstract
*Blueberry phenolics are associated with cognitive enhancement in supplemented healthy older adults
*Prospective association between adherence to the Mediterranean diet and hepatic steatosis: the Swiss CoLaus cohort study Full Text

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*The effects of resistance training with or without peanut protein supplementation on skeletal muscle and strength adaptations in older individuals Full Text
*Effects of dance on cognitive function in older adults: a systematic review and meta-analysis
What makes hard workouts so effective Abstract

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.
Anti-Hyperuricemic Effects of Astaxanthin by Regulating Xanthine Oxidase, Adenosine Deaminase and Urate Transporters in Rats Full Text
Anti-diabetic effects of astaxanthin on an STZ-induced diabetic model in rats Full Text
Astaxanthin Supplementation Enriches Productive Performance, Physiological and Immunological Responses in Laying Hens Full Text

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.
*The Efficacy of the Novel Bioavailable Curcumin (Cureit) in the Management of Sarcopenia in Healthy Elderly Subjects: A Randomized, Placebo-Controlled, Double-Blind Clinical Study
The role of curcumin in aging and senescence: Molecular mechanisms Full Text
Anti-Viral Potential and Modulation of Nrf2 by Curcumin: Pharmacological Implications 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 Regulates Gut Microbiota and Exerts Neuroprotective Effect on Mouse Model of Parkinson's Disease Full Text
Fisetin Alleviated Bleomycin-Induced Pulmonary Fibrosis Partly by Rescuing Alveolar Epithelial Cells From Senescence Full Text
Nutraceutical Approaches of Autophagy and Neuroinflammation in Alzheimer's Disease: A Systematic Review Full Text

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.
Melatonin: finally, a supplement that actually boosts memory Full Text
Melatonin protects against oxybenzone-induced deterioration of mouse oocytes during maturation Full Text
The effects of melatonin daily supplementation to aged rats on the ability to withstand cold, thermoregulation and body weight

Nicotinamide MonoNucleotide (NMN) – newer NAD+ precursor. I take 250 – 500mg on days I exercise.
Neuroprotective effects and mechanisms of action of nicotinamide mononucleotide (NMN) in a photoreceptor degenerative model of retinal detachment Full Text
Nicotinamide mononucleotide (NMN) protects bEnd.3 cells against H 2 O 2 -induced damage via NAMPT and the NF-κB p65 signalling pathway Full Text
Subacute Toxicity Study of Nicotinamide Mononucleotide via Oral Administration Full Text

Nicotinamide Riboside (NR) – NAD+ precursor.
Protective Effects of Nicotinamide Riboside on H 2 O 2-induced Oxidative Damage in Lens Epithelial Cells
Targeting CD38-dependent NAD + metabolism to mitigate multiple organ fibrosis 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 Aβ 1-42 -induced cognitive dysfunction via inhibition of oxidative stress by activating Nrf2 signaling pathway

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.
*Resveratrol-Based Multivitamin Supplement Increases Sperm Concentration and Motility in Idiopathic Male Infertility: A Pilot Clinical Study Full Text
*Efficacy of resveratrol supplementation in patients with nonalcoholic fatty liver disease: A systematic review and meta-analysis of clinical trials
*Effects of Oral Resveratrol Supplementation on Glycogen Replenishment and Mitochondria Biogenesis in Exercised Human Skeletal Muscle Full Text