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October 2019 Longevity Review

Posted by Chris Pollyanna , 21 November 2019 · 2,547 views

review supplements alpha-ketoglutarate telomeres senolytics

October 2019 Longevity Review

 

Hello and welcome once again to this month’s longevity review. There’s interesting news concerning a new supplement, more evidence for the importance of telomeres as well as the usual avalanche of studies in the supplemental section. If you look in the Epigenetic section, there are a couple of pre-print papers providing support for the book I briefly reviewed last month – Lifespan. In Odds & Sods, you’ll also find a potentially worrying effect of the blue light coming from our screens, though thankfully there is a simple & quick solution – although it’s never good to read too much into a single study, I’ve put a blue light filter on all of my devices (just in case).

 

In local news the Toronto Longevity Association successfully held its first meet-up, where despite the cold driving rain, five of us met up and had a most enjoyable evening of conversation. From small acorns… As mentioned in last month’s newsletter, I’ve also now started helping the Life Extension Advocacy Foundation (LEAF) get information for their monthly round-up. Their big news was the successful completion of their Mitomouse crowd funding campaign, which reached the $75,000 stretch goal – a big thank you to everyone who donated! Last but not least my local MP got re-elected. When I met him last year, he was interested in and supportive of what I was doing. Now that he’s going to be around and in power for at least four years, I intend to leverage him into raising awareness of longevity and the need for more funding within the Canadian government.

 

Follow me on Twitter @ChrisPollyanna1 for the latest updates!

 

Finally – please feel free to forward this email to anyone who might be interested, and please let me know if anyone would like to be included in my mailing list! Also, any feedback is greatly appreciated. :-D
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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.

 

October Round-Up:

  • Top news this month is a new substance, alpha-ketogluterate, which I had never heard about before, but which seems to extend lifespan and reduce frailty in mice. I heard about this from a news release for a new supplement, which initially raised my suspicions that this was mere marketing blather. However, after tracking down the source, it turned out to be a pre-print publication from a very reputable group of scientists from the Buck Institute. I’m sure that once it gets published, it will be making headlines in the general scientific press. As for the supplement, it is rather pricey - $150USD for a month’s supply – certainly outside of my price range, but worth keeping an eye on in the future:
Alpha-ketoglutarate, an endogenous metabolite, extends lifespan and compresses morbidity in aging mice
  • Telomeres, the protective caps at the end of our chromosomes, are a fierce topic of debate in the longevity field. The question is whether or not their shortening over time is a cause or an effect of the aging process. This interesting paper, by the leading researcher in the field, seems to imply that there is some causative effect, though this will not assuage the critics. Here mice have been engineered to have much longer telomeres than they would naturally, with the effect of lengthening their lifespans:
Mice with hyper-long telomeres show less metabolic aging and longer lifespans Full Text
As a side note, there was also an announcement that an unconnected company was starting a trial in humans of a gene therapy to lengthen the volunteer’s telomeres. It will be interesting to see if anything comes of it: https://genomecontex...-of-telomerase/
  • One potential way to extend life would be to replace our failing organs with freshly grown ones. This has been the Holy Grail for regenerative medicine, especially in the light of the lengthy waiting lists for organ transplants. (Though in my opinion it might be superseded by in situ organ repair via stem cells/reprogramming etc before it comes into practice) The following paper marks another step towards the creation of fully functioning organs:
Complex organ models grown in the lab Full Text
  • Despite the incredible advances shown so far, we are still at the early stages of the longevity revolution, and far more funding is desperately needed. Not only that, but the entire scientific & medical community needs to come around to the idea that ageing is something that can and should be tackled. Above that, policy makers & governments who hold the purse strings and control the regulations need to be brought on board as well. The following links are an indication that increasing numbers of scientists hold this view and that institutions are beginning to follow their lead.
The first link is to a special issue of Public Policy& Aging Report, which has a number of interesting open access papers covering everything from putting the case for fighting ageing, to regulatory pathways for anti-ageing drugs and international investments in the field among others. The second is a clarion call from leading scientists and the third is a new international initiative to tackle ageing:
Is Aging Still a Disease? Perspectives from Geroscience
Experts call on the World Health Organization, governments and medical communities to develop common classifications and systems to diagnose and treat age-related diseases LEAF view
Enabling Healthful Aging for All — The National Academy of Medicine Grand Challenge in Healthy Longevity
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Video to watch:
RAADfest is an annual gathering of life-extension enthusiasts which combines bona fide science with certain “fringier” elements. It’s got a bit too much evangelical fervor for my tastes, but I’m not here to criticise others, and anything which helps grow our movement is to be welcomed. Bill Faloon is the founder of the LifeExtension supplement company and Age-Reversal.net, which is a useful public forum for self-experimenters. Here he gives his overview of the current state of the field from a more lay person’s perspective as well as announcing an intriguing new trial aimed at evaluating current best practices in longevity:
Bill Faloon’s 2019 RAADfest Presentation
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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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October 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.
Restoration of the renin-angiotensin system balance is a part of the effect of fasting on cardiovascular rejuvenation: Role of age and fasting models.
Time-restricted eating and age-related muscle loss Full Text
A nutritional memory effect counteracts the benefits of dietary restriction in old mice

 

Diet – let food be thy medicine…
*Red Wine Consumption and Cardiovascular Health Full Text
*Effects of Intake of Apples, Pears, or Their Products on Cardiometabolic Risk Factors and Clinical Outcomes: A Systematic Review and Meta-Analysis. Full Text
*Higher dietary diversity scores and protein-rich food consumption were associated with lower risk of all-cause mortality in the oldest old.
*Daily steps and diet, but not sleep, are related to mortality in older Australians. Full Text

 

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*Effects of High-Intensity Interval Training and Isoinertial Training on Leg Extensors Muscle Function, Structure, and Intermuscular Adipose Tissue in Older Adults Full Text
*Exercise Snacking to Improve Muscle Function in Healthy Older Adults: A Pilot Study. 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.
The Effect of Astaxanthin on Random Pattern Skin Flaps

 

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.
The antioxidant curcumin postpones ovarian aging in young and middle-aged mice.
Curcumin, Gut Microbiota, and Neuroprotection. Full Text
Curcumin as a Therapeutic Strategy in Liver Diseases Full Text
Theracurmin (Highly Bioavailable Curcumin) Prevents High Fat Diet-Induced Hepatic Steatosis Development in Mice. Full Text

 

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 Alleviates Atrial Inflammation, Remodeling, and Vulnerability to Atrial Fibrillation after Myocardial Infarction. Full Text
MMP-2 and MMP-9 mediate cigarette smoke extract-induced epithelial-mesenchymal transition in airway epithelial cells via EGFR/Akt/GSK3β/β-catenin pathway: Amelioration by fisetin.

 

Nicotinamide MonoNucleotide (NMN) – newer NAD+ precursor. I take 250 – 500mg on days I exercise.
Melatonin and Nicotinamide Mononucleotide Attenuate Myocardial Ischemia/Reperfusion Injury via Modulation of Mitochondrial Function and Hemodynamic Parameters in Aged Rats
Nicotinamide Mononucleotide and Melatonin Alleviate Aging-induced Cognitive Impairment via Modulation of Mitochondrial Function and Apoptosis in the Prefrontal Cortex and Hippocampus

 

Nicotinamide Riboside (NR) – NAD+ precursor.
NAD+ repletion inhibits the endothelial-to-mesenchymal transition induced by TGF-β in endothelial cells through improving mitochondrial unfolded protein response.

 

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 Astrocytic Inflammation and Neuronal Oxidative Injury After Ischemia-Reperfusion by Inhibiting NF-κB Phosphorylation. Full Text
Browning Effects of a Chronic Pterostilbene Supplementation in Mice Fed a High-Fat Diet. Full Text
Effects of pterostilbene on diabetes, liver steatosis and serum lipids
Protective effect of pterostilbene on concanavalin A-induced acute liver injury

 

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.
*Post-Exercise Recovery Following 30-Day Supplementation of Trans-Resveratrol and Polyphenol-Enriched Extracts. Full Text
Evaluation of the therapeutic activity of melatonin and resveratrol in Inflammatory Bowel Disease: A longitudinal PET/CT study in an animal model.
Therapeutic effect of resveratrol supplementation on oxidative stress: a systematic review and meta-analysis of randomised controlled trials.
Effects of resveratrol on learning and memory in rats with vascular dementia

 

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 (see last month’s newsletter).
Metformin Restores CNS Remyelination Capacity by Rejuvenating Aged Stem Cells. Full Text
Metformin Alters Locomotor and Cognitive Function and Brain Metabolism in Normoglycemic Mice. Full Text
Metformin abrogates age-associated ovarian fibrosis.

 

Rapamycin (sirolimus) – first drug proven to increase the health & lifespan of mice. Currently used for organ transplantation and against cancer. Was taking 5mg (or only 3.23mg?) once a week before my source’s legitimacy was questioned, stopped & have yet to resume.
Rapamycin for longevity: opinion article. Full Text
Calorie-Restriction-Induced Insulin Sensitivity Is Mediated by Adipose mTORC2 and Not Required for Lifespan Extension. Full Text
Iron Overload Impairs Autophagy: Effects of Rapamycin in Ameliorating Iron-Related Memory Deficits.
Autophagy induction by rapamycin ameliorates experimental colitis and improves intestinal epithelial barrier function in IL-10 knockout mice.
Efficacy and safety of sirolimus in the treatment of vascular anomalies: A systematic review.
Differential effects of various genetic mouse models of the mechanistic target of rapamycin complex I inhibition on heart failure.

 

Still In The Lab

 

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:
Identification and characterization of Cardiac Glycosides as senolytic compounds Full Text
Cellular senescence in development, regeneration and disease Full Text

 

Epigenetic Cellular Reprogramming/Aging Clocks – 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:

 

The two pre-print papers from David Sinclair, laying some of the framework for his Information Theory of Aging as outlined in his book Lifespan, which I reviewed last month:

Epigenetic Age Reversal by Cell-Extrinsic and Cell-Intrinsic Means. Full Text
Different epigenetic clocks reflect distinct pathophysiological features of multiple sclerosis. Full Text
Epigenetic clocks and allostatic load reveal potential sex-specific drivers of biological ageing.
DNA methylation age and physical and cognitive ageing 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. I’m very much on the fence about this. There were however a large number of studies this month, so I decided to group them together.
*Genetically Increased Telomere Length and Aging-related Traits in the UK Biobank
*Telomere length and cognitive function: Differential patterns across sociodemographic groups.
*The association of mean telomere length with all-cause, cerebrovascular and cardiovascular mortality Full Text
*Diet, physical activity and telomere length in adults Full Text

 

Odds & Sods

*Dog Ownership and Survival
*Mortality Risk Associated With Personality Facets of the Big Five and Interpersonal Circumplex Across Three Aging Cohorts.
*Intermittent Hypoxia-Hyperoxia Training Improves Cognitive Function and Decreases Circulating Biomarkers of Alzheimer's Disease in Patients with Mild Cognitive Impairment: A Pilot Study. Full Text
Downregulation of the inflammatory network in senescent fibroblasts and aging tissues of the long-lived and cancer-resistant subterranean wild rodent, Spalax Full Text
Aging progression of human gut microbiota Full Text
Anti-Ageing Gene Therapy: Not so Far Away?
Trehalose administration in C57BL/6N old mice affects healthspan improving motor learning and brain anti-oxidant defences in a sex-dependent fashion: A pilot study. Full Text
Vitamin D in physiological and pathological aging: Lesson from centenarians.
Low-dose quercetin positively regulates mouse healthspan Full Text
Regulation of lifespan by neural excitation and REST
Mechanisms by which PE21, an extract from the white willow Salix alba, delays chronological aging in budding yeast Full Text
Transcriptome Characterization of Reverse Development in Turritopsis dohrnii (Hydrozoa, Cnidaria) Full Text







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