February 2020 Longevity Review

Posted by Chris Pollyanna , 09 March 2020 · 3,524 views

longevity supplements lifestyle nmn rapamycin stem cells crispr

Hello and welcome again to this month’s longevity review. After a seeming month long hiatus, where the longevity focus seemed to shift to lifestyle interventions, February saw a marked return to exciting scientific advances, with a cell based therapy showing lifespan extension & the tantalizing glimpse that it will eventually be possible to rejuvenate people at any age. Check out the round-up for further details. I’ve also yet again expanded the supplemental section to include other interesting areas such as the microbiome & skincare getting their own sections. I hope it won’t get too long and unwieldy, but I thought it better for the info to be freed than languish on my hard drive.

Personally, it has been a month of good progress. I paid to join Meetup.com and had the second meeting of the Toronto Longevity Association through them, meeting some new & interesting people in the process. Also met some other longevity enthusiasts via a different Meetup group. It is really heartening to see the longevity community slowly expanding in Toronto, as a couple of years ago I didn’t know anyone else here interested in this.

More importantly, I met my wonderful MP, Nathaniel Erskine-Smith, for the second time, giving him a brief update as well as copies of my yearly reviews. Meeting him for the first time had a big impact on me, as he took me seriously and showed an interest in this field. It was the validation and encouragement that I needed at the time. I hope that he can become an ally of ours going forward. Speaking of which, I’ve created a database of all the research institutes & researchers in Southern Ontario connected, however tenuously, to longevity. Over the coming months I shall be contacting them (over 300!) with the intention of bringing them into our community and also to get us even closer to the cutting edge, as there is some amazing research taking place here. Finally, provided that Corvid-19 doesn’t scupper everything – I will be going to Undoing Aging 2020 in Berlin in May as part of the LEAF team, where I will be tasked, amongst other things, to interview some scientists! How cool is that??

Follow me on Twitter @ChrisPollyanna1 for the latest news!

And please join my longevity Facebook group.

If you have any comments or thoughts, please add them to the comments section below.

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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.

February Round-Up:

The most exciting development in the past month was this cell based therapy, whereby young blood producing stem cells were given to old mice. This increased their average lifespan by 12% (& maximum if you eye ball the graph) and reduced other aspects of ageing. Equally importantly, their new method was a lot less toxic than previous ones, so making it more translatable to us. I can easily foresee a future where our own blood stem cells are harvested, rejuvenated outside the body & then given back to us.
Mobilization-based transplantation of young-donor hematopoietic stem cells extends lifespan in mice. Full Text

Why am I so confident that our blood stem cells could be rejuvenated? Well, the following example should make it abundantly clear. Here, cells from a 114 year old supercentenarian were successfully rejuvenated and turned into youthful stem cells! It shows that extreme old age is not a barrier to cellular rejuvenation. Most excitingly, what at present can only be done in individual cells, will eventually be done to whole organisms.
114 year-old cells converted to pluripotent stem cells & cellular age reversed Full Text

Much more near term (in fact you can order this online already) is the following study, where Nicotinamide MonoNucleuotide (NMN) was used to restore fertility in aged animals. The benefits extended to the offspring, who showed more lean body mass. However, don’t try this at home, as lower doses turned out to be better than higher ones & we have no idea yet what optimal human dosing is. Boosting NAD+ Levels Restores Fertility in Aged Mice Full Text
Chronic inflammation is not only a sign, but also a cause of ageing, and in this more basic science paper scientists think they have found an “off” switch for it. Interestingly enough, it involves genetic pathways which are influenced by NAD+ precursors such as NMN mentioned above.
Sirtuins Mitigate Chronic Inflammation and Insulin Resistance Abstract

Although this is not directly related to longevity, the technology behind it will certainly be used for that purpose – CRISPR gene editing is the recent addition to the geneticist’s armatorium, which has made genetic manipulation massively easier to undertake. Here are the first in human results, showing that the genetically altered immune cells can survive extended periods of time after being returned to the body. Circling back to our first story, I can see CRISPR being used to further enhance our rejuvenated cells.
CRISPR Edited Immune Cells Successful in First U.S. Clinical Trial Full Text

Maybe this needs its own section (note to self!), but here is a mini round-up of developments in the commercial sphere – after all, it’s no good for developments to be sitting in the lab: someone needs to commercialise them. In alphabetical order, Alkahest have announced the initiation of a Phase 2b trial in Parkinson’s disease. They have another Parkinson’s trial using a young plasma fraction, but here they are using oral antibodies to block the actions of a substance which increases with age in the blood. George Church’s Rejuvenate Bio are starting their combination gene therapy trial in dogs, while Unity Biotech have an update on their senolytic treatments which have also entered Phase 2. A nice update of other companies’ progress is provided by Reason’s report from the 2020 Longevity Therapeutics Conference. Finally, if you want a one-stop shop to see where commercial developments stand, head on over to LEAF’s Rejuvenation Roadmap, which is updated frequently. As you can see, there’s more than a few companies hard at work in this field!

Popular podcast host Joe Rogan interviews longevity “wizard” in chief Aubrey de Grey about the state of ageing research. In this interview Aubrey is quite optimistic, believing that a decisive turning point could be only 3 – 5 years away:
Joe Rogan Experience #1432 - Aubrey de Grey

Bonus Canadian content video:

National treasure David Suzuki (83) takes a look at “healthy ageing” and how well he is doing:
Aging Well Suzuki Style (only available in Canada)
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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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February 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.
*Energy Restriction Enhances Adult Hippocampal Neurogenesis-Associated Memory after Four Weeks in an Adult Human Population with Central Obesity; a Randomized Controlled Trial. Full Text
*When should you eat to manage your weight? Breakfast, not late-night snacks Full Text
How caloric restriction prevents negative effects of aging in cells Full Text
Anti-aging Effects of Calorie Restriction (CR) and CR Mimetics based on the Senoinflammation Concept. Full Text

Diet – let food be thy medicine…
*Cocoa to Improve Walking Performance in Older People With Peripheral Artery Disease: The Cocoa-Pad Pilot Randomized Clinical Trial. Full Text
*Mediterranean diet for one year promotes gut bacteria linked to 'healthy aging' Abstract. Full Text
Mediterranean diet ingredient may extend life Full Text
*Dose-Response Relation between Tea Consumption and Risk of Cardiovascular Disease and All-Cause Mortality: A Systematic Review and Meta-Analysis of Population-Based Studies. Full Text
*Beneficial Effects of Walnuts on Cognition and Brain Health Full Text

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*Instability Resistance Training improves Working Memory, Processing Speed and Response Inhibition in Healthy Older Adults: A Double-Blinded Randomised Controlled Trial. Full Text
*Aerobic exercise training linked to enhanced brain function Full Text
*Regular aerobic exercise improves sexual function assessed by the Aging Males' Symptoms questionnaire in adult men.
*High Intensity Interval Training Does Not Have Compensatory Effects on Physical Activity Levels in Older Adults. 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 carotinoid, it has anti-oxidative, anti-inflamatory, anti-cancer, neuro-protective and skin-protective qualities. I take 4 or 8 mg intermittently.
*A combined effect of Cavacurcumin, Eicosapentaenoic acid (Omega-3s), Astaxanthin and Gamma -linoleic acid (Omega-6) (CEAG) in healthy volunteers- a randomized, double-blind, placebo-controlled study.
*Effects of Lutein and Astaxanthin Intake on the Improvement of Cognitive Functions among Healthy Adults: A Systematic Review of Randomized Controlled Trials. Full Text
Favorable Effects of Astaxanthin on Brain Damage due to Ischemia-Reperfusion Injury
Astaxanthin anticancer effects are mediated through multiple molecular mechanisms: A systematic review
Astaxanthin attenuates oxidative stress and inflammatory responses in complete Freund-adjuvant-induced arthritis 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 bio-availability.
*Effect of curcumin supplementation on disease severity in patients with liver cirrhosis: A randomized controlled trial.
*Modulation of Exercise-Induced Muscle Damage, Inflammation, and Oxidative Markers by Curcumin Supplementation in a Physically Active Population: A Systematic Review. Full Text
*Effects of Turmeric on Cardiovascular Risk Factors, Mental Health, and Serum Homocysteine in Overweight, Obese Females
Pharmacokinetics and pharmacodynamics of three oral formulations of curcumin in rats
Mutual Two-Way Interactions of Curcumin and Gut Microbiota

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.
Fisetin protects against cardiac cell death through reduction of ROS production and caspases activity. 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 anti-oxidant. 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.
Role of melatonin in prevention of age-related hearing loss Full Text
Melatonin attenuates vascular calcification by activating autophagy via an AMPK/mTOR/ULK1 signaling pathway.

Nicotinamide MonoNucleotide (NMN) – newer NAD+ precursor. I take 250 – 500mg on days I exercise.
NMN Rejuvenates the Mitochondria of Old Mice Abstract
NAD+ precursors protect corneal endothelial cells from UVB-induced apoptosis.
Nicotinamide Riboside (NR) – NAD+ precursor.
Induction of the nicotinamide riboside kinase NAD+ salvage pathway in a model of sarcoplasmic reticulum dysfunction. Full Text
Long noncoding RNA SNHG12 integrates a DNA-PK-mediated DNA damage response and vascular senescence.

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.
Occurrence, bioavailability, anti-inflammatory and anti-cancer effects of pterostilbene sci-hub.tw/10.1021/acs.jafc.9b07860

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.
*Acute resveratrol supplementation in coronary artery disease: towards patient stratification.
*The effects of resveratrol on lipid profiles and liver enzymes in patients with metabolic syndrome and related disorders: a systematic review and meta-analysis of randomized controlled trials. Full Text
A review on the potential of Resveratrol in prevention and therapy of diabetes and diabetic complications Full Text
Resveratrol protects against ethanol-induced impairment of insulin secretion in INS-1 cells through SIRT1-UCP2 axis.
Suppression of glomerular damage and apoptosis and biomarkers of acute kidney injury induced by acetaminophen toxicity using a combination of resveratrol and quercetin

Spermidine – found in wheat germ and a potent inducer of autophagy, it works in synergy with Resveratrol. I try to eat a few of teaspoons of wheat germ every day in my berry & nut breakfast.

Other available supplements
A Novel Micronutrient Blend Mimics Calorie Restriction Transcriptomics in Multiple Tissues of Mice and Increases Lifespan and Mobility in C. elegans Full Text
Synergic Effects of Berberine and Curcumin on Improving Cognitive Function in an Alzheimer's Disease Mouse Model.
Choline as a prevention for Alzheimer’s disease Full Text
Vitamin D and Endothelial Function Full Text
Postural Balance Effects Associated with 400, 4000 or 10,000 IU Vitamin D3 Daily for Three Years: A Secondary Analysis of a Randomized Clinical Trial. Full Text
Potential Implications of Quercetin and its Derivatives in Cardioprotection 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.
Metformin: current clinical applications in nondiabetic patients with cancer. Full Text
Metformin coordinates osteoblast/osteoclast differentiation associated with ischemic osteonecrosis. Full Text
Antidiabetic Drug Metformin Ameliorates Depressive-Like Behavior in Mice with Chronic Restraint Stress via Activation of AMP-Activated Protein Kinase. Full Text

Rapamycin (sirolimus) – first drug proven to increase the health & lifespan of mice. Currently used for organ transplantation and against cancer.
*Modulation of the antidepressant effects of ketamine by the mTORC1 inhibitor rapamycin. Full Text
*Successful sirolimus treatment of patients with pure red cell aplasia complicated with renal insufficiency.
*The efficacy and safety of topical rapamycin/calcitriol for facial angiofibromas in patients with tuberous sclerosis complex: a prospective, double-blind randomized clinical trial.
Rapamycin preserves the primordial follicle pool during cisplatin treatment in vitro and in vivo.
Up-regulating autophagy by targeting the mTOR-4EBP1 pathway: a possible mechanism for improving cardiac function in mice with experimental dilated cardiomyopathy. Full Text

Other Areas of Interest

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:
An epigenetic clock for human skeletal muscle Full Text
Longitudinal trajectories, correlations and mortality associations of nine biological ages across 20-years follow-up Full Text
Mortality: The challenges of estimating biological age Full Text
Mitochondria and aging in older individuals: an analysis of DNA methylation age metrics, leukocyte telomere length, and mitochondrial DNA copy number in the VA normative aging study. Full Text
DNA methylation-based measures of accelerated biological ageing and the risk of dementia in the oldest-old: a study of the Lothian Birth Cohort 1921. 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:
Two conserved epigenetic regulators prevent healthy ageing Researchers identify novel anti-aging targets
The ageing epigenome and its rejuvenation Belmonte sci-hub.tw/10.1038/s41580-019-0204-5

Microbiome – all the little critters living in and on us have a major influence on our health and potentially our longevity.
*Human Skin, Oral, and Gut Microbiomes Predict Chronological Age Full Text
The Microbiome of the Meibum and Ocular Surface in Healthy Subjects Full Text
It's the fiber, not the fat: significant effects of dietary challenge on the gut microbiome. 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:
Therapeutic senescence via GPCR activation in synovial fibroblasts facilitates resolution of arthritis. Full Text
Targeted reduction of senescent cell burden alleviates focal radiotherapy-related bone loss.
Discovery, Development, and Future Application of Senolytics: Theories and Predictions. Full Text
Cellular Senescence in Neurodegenerative Diseases Full Text
Potential Role of Cellular Senescence in Asthma 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.
Efficacy and safety of a 3-in-1 antiaging night facial serum containing melatonin, bakuchiol, and ascorbyl tetraisopalmitate through clinical and histological analysis
Beauty from within: Oral administration of a sulfur-containing supplement methylsulfonylmethane improves signs of skin ageing. Full Text
Four-Weeks Daily Intake of Oral Collagen Hydrolysate Results in Improved Skin Elasticity, Especially in Sun-Exposed Areas: A randomized, double-blind, placebo-controlled trial

Stem Cells & Exosomes (small packets of information released by cells)
Inhalation therapy shows promise against pulmonary fibrosis in mice, rats Full Text
Transplantation of Directly Reprogrammed Human Neural Precursor Cells Following Stroke Promotes Synaptogenesis and Functional Recovery. 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.
Association of Leukocyte Telomere Length With Mortality Among Adult Participants in 3 Longitudinal Studies. Full Text
The Impact of Health Promotion Interventions on Telomere Length: A Systematic Review.
Physical Activity and Telomeres in Old Age: A Longitudinal 10-Year Follow-Up Study.
The Use of Natural Agents to Counteract Telomere Shortening: Effects of a Multi-Component Extract of Astragalus mongholicus Bunge and Danazol. Full Text
Faster and Healthier: Relationship between Telomere and Performance in Master Athletes.

Young Blood Factors or other Heterochronic Transplantations – 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:
Young Bone Marrow Preserves Cognition in Mice Full Text
MANF delivery improves retinal homeostasis and cell replacement therapies in ageing mice.

Odds & Sods
Vascular endothelium-targeted Sirt7 gene therapy rejuvenates blood vessels and extends life span in a Hutchinson-Gilford progeria model. Full Text
Pan-mammalian analysis of molecular constraints underlying extended lifespan. Full Text
Successful aging: insights from proteome analyses of healthy centenarians. Full Text
Meta-analytic evidence for the anti-aging effect of hormesis on Caenorhabditis elegans Full Text
The turquoise killifish: a genetically tractable model for the study of aging. Full Text
Researchers discover how cells clear misfolded proteins from tissues
Brain cells protect muscles from wasting away
Drug synergy as a strategy for compression of morbidity in a Caenorhabditis elegans model of Alzheimer’s disease
Partial Inhibition of RNA Polymerase I Promotes Animal Health and Longevity. Full Text
'Resetting' immune cells improves traumatic brain injury recovery in preclinical trials
Tet1 Deficiency Leads to Premature Reproductive Aging by Reducing Spermatogonia Stem Cells and Germ Cell Differentiation. Full Text
Artificial intelligence yields new antibiotic Full Text