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December 2019 Longevity Review

Posted by Chris Pollyanna , 06 January 2020 · 816 views

longevity review supplements gdf11 rapamycin intermittent fasting

December 2019 Longevity Review

 

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 :blush:)
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

 

================================================================================================================================================================================================================================================================

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.

 

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.
Spermidine protects from age-related synaptic alterations at hippocampal mossy fiber-CA3 synapses. Full Text
The curious case of polyamines: spermidine drives reversal of B cell senescence. Full Text

 

Other available supplements
*Enriched Marine Oil Supplements Increase Peripheral Blood Specialized Pro-Resolving Mediators Concentrations and Reprogram Host Immune Responses Full Text
Quercetin, Epigallocatechin Gallate, Curcumin, and Resveratrol: From Dietary Sources to Human MicroRNA Modulation. Full Text
Combination treatment of berberine and solid lipid curcumin particles increased cell death and inhibited PI3K/Akt/mTOR pathway of human cultured glioblastoma cells more effectively than did individual treatments. Full Text
Targeting Mitogen-Activated Protein Kinases by Natural Products: A Novel Therapeutic Approach for Inflammatory Bowel Diseases
Network Pharmacology Approach uncovering Pathways involved in targeting Hsp90 through Curcumin and Epigallocatechin to control Inflammation.
*The Effects of Lutein and Zeaxanthin Supplementation on Brain Morphology in Older Adults: A Randomized, Controlled Trial. Full Text
l-Theanine attenuates liver aging by inhibiting advanced glycation end products in d-galactose-induced rats and reversing an imbalance of oxidative stress and inflammation.
Dietary Selenium Supplementation Ameliorates Female Reproductive Efficiency in Aging Mice. Full Text
Intake of omega-3 formulation EPA:DHA 6:1 by old rats for 2 weeks improved endothelium-dependent relaxations and normalized the expression level of ACE/AT1R/NADPH oxidase and the formation of ROS in the mesenteric artery.
Melatonin protects blood-brain barrier integrity and permeability by inhibiting matrix metalloproteinase-9 via the NOTCH3/NF-κB pathway. Full Text

 

Prescription Supplements & Other

 

MetforminAnti-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).
Secret behind diabetes drug's benefits revealed
Metformin Treatment for Diabetes Mellitus Correlates with Progression and Survival in Colorectal Carcinoma Full Text
Metformin promotes innate immunity through a conserved PMK-1/p38 MAPK pathway. Full Text
Emerging Neuroprotective effect of Metformin in Parkinson's disease: A Molecular crosstalk.
Metformin ameliorates bile duct ligation-induced acute hepatic injury via regulation of ER stress.

 

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.
Targeting mTOR and Metabolism in Cancer: Lessons and Innovations Full Text
Treatment with Rapamycin Can Restore Regulatory T Cell Function in IPEX Patients.
mTORC1 and mTORC2 Differentially Regulate Cell Fate Programs to Coordinate Osteoblastic Differentiation in Mesenchymal Stromal Cells. Full Text
Rapamycin treatment maintains developmental potential of oocytes in mice and follicle reserve in human cortical fragments grafted into immune-deficient mice.

 

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:
Senotherapeutics: Targeting senescence in idiopathic pulmonary fibrosis.
Early removal of senescent cells protects retinal ganglion cells loss in experimental ocular hypertension. Full Text
Senolytics and Senostatics: A Two-Pronged Approach to Target Cellular Senescence for Delaying Aging and Age-Related Diseases. Full Text
Senescent cell turnover slows with age providing an explanation for the Gompertz law. Full Text
Cellular senescence and chronological age in various human tissues: A systematic review and meta-analysis. Full Text

 

Ageing Clocks & other Biomarkers of Ageingthe 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:
Epigenetics of aging and disease: a brief overview. Full Text
Patterns of Aging Biomarkers, Mortality, and Damaging Mutations Illuminate the Beginning of Aging and Causes of Early-Life Mortality. Full Text
Emerging Insights into the Metabolic Alterations in Aging Using Metabolomics Full Text
An epigenetic predictor of death captures multi-modal measures of brain health. Full Text
Comprehensive longitudinal study of epigenetic mutations in aging Full Text
A genomic predictor of lifespan in vertebrates Full Text
Measuring biological aging in humans: A quest Full Text
Undulating changes in human plasma proteome profiles across the lifespan. Sciencedaily.com
An epigenetic predictor of death captures multi-modal measures of brain health. 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.
Leukocyte telomere length and serum polyunsaturated fatty acids, dietary habits, cardiovascular risk factors and features of myocardial infarction in elderly patients.
Telomere length associations with cognition depend on Alzheimer's disease biomarkers. Full Text
Telomerase Does Not Improve DNA Repair in Mitochondria upon Stress but Increases MnSOD Protein under Serum-Free Conditions. Full Text

 

Odds & Sods
*Does Blood Flow Restriction Therapy in Patients Older Than Age 50 Result in Muscle Hypertrophy, Increased Strength, or Greater Physical Function? A Systematic Review
Advanced Glycation End Products (AGEs) May Be a Striking Link Between Modern Diet and Health. Full Text
MicroRNA-145 engineered bone marrow-derived mesenchymal stem cells alleviated erectile dysfunction in aged rats. Full Text
Understanding muscle regenerative decline with aging: new approaches to bring back youthfulness to aged stem cells. Full Text
Using deep learning to associate human genes with age-related diseases Full Text
Aerosol inhalation of a hydrogen-rich solution restored septic renal function. Full Text
Methylene blue inhibits Caspase-6 activity, and reverses Caspase-6-induced cognitive impairment and neuroinflammation in aged mice. Full Text
The Unexplored World of Human Virome, Mycobiome, and Archaeome in Aging Full Text
Impact of oxytocin on skin ageing Full Text
*The art of life and death: 14 year follow-up analyses of associations between arts engagement and mortality in the English Longitudinal Study of Ageing







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