September 2020 Longevity Review
supplements metformin nad+ rapamycin fasting longevity health
Hello and welcome again to this month’s longevity review. After last month’s focus on more further off longevity treatments such as gene therapy, this month the focus has shifted to more readily available drugs. Old stalwart Metformin has more evidence to its efficacy, while fellow diabetes drug Canagliflozin has been shown to increase the lifespan of male mice. Furthermore, a new and very expensive supplement has also been shown to also increase murine life and healthspan.
For me, there’s finally light at the end of the tunnel workwise, so hopefully I’ll soon be able to devote more time to longevity related advocacy, which I’ve had to neglect the last few months. I’m also mulling over whether or not to get the new supplement mentioned above for my parents, but at more than $100USD per month, it’s giving me pause for thought!
Stay safe!
Follow me on Twitter @ChrisPollyanna1 for the latest updates.
Please also join my longevity Facebook group.
Finally – any comments or feedback is greatly appreciated!
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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:
Metformin has long been touted as an anti-ageing drug and it certainly is the most widely consumed among longevity researchers. Proof of its efficacy will have to wait for the now delayed TAME trial, however this study seems to show that Metformin slowed cognitive decline over 6 years.
*Metformin Use Is Associated With Slowed Cognitive Decline and Reduced Incident Dementia in Older Adults With Type 2 Diabetes: The Sydney Memory and Ageing Study
The Interventions Testing Program remains the gold standard for lifespan interventions, so when they produce a positive result it is worth paying attention. In this case it is a common diabetes drug Canagliflozin, a SGLT2 inhibitor, which extended median survival of male mice by 14%, and maximum by 9%.
Canagliflozin extends lifespan in genetically heterogeneous male but not female mice Full Text
Although not up to the rigorous standards of the ITP, Alpha-ketoglutarate was shown by a well respected group of researchers to modestly increase lifespan by 5 -10% in mice. However, there was a much greater improvement in healthspan, including the retention of hair colouring.
Alpha-Ketoglutarate Extends Healthspan in Aging Mice Full Text
I’ve talked about how important it is to prevent immune system decline, and how targeting the Thymus provides an avenue for that. Here, stem cells taken from umbilical cords have shown to do just that.
Umbilical cord mesenchymal stem cells protect thymus structure and function in aged C57 mice by downregulating aging-related genes and upregulating autophagy- and anti-oxidative stress-related genes Full Text
Although this last item is only a press release, I’ve included it as it provides hope that noise induced hearing loss might be treatable.
Frequency Therapeutics Presents Results Demonstrating Sustained Improvement in Hearing Loss Patients Treated with FX-322
Covid-19 Longevity Related Papers:
Pharmacoinformatics and hypothetical studies on allicin, curcumin, and gingerol as potential candidates against COVID-19-associated proteases Full Text
Curcumin, a traditional spice component, can hold the promise against COVID-19? Full Text
Potential therapeutic effects of Resveratrol against SARS-CoV-2
Repurposing existing drugs for COVID-19: an endocrinology perspective Full Text
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Video to watch:
Another month, another conference, this time the 7th Aging Research and Drug Discovery conference, whose videos have now been posted. There is quite a selection to choose from with over 40 videos available!
ARDD 2020 Videos
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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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September 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.
*Effects of Time-Restricted Eating on Weight Loss and Other Metabolic Parameters in Women and Men With Overweight and Obesity
*Time-restricted feeding improves health without altering the body's core clock Full Text
*Effects of caloric restriction on human physiological, psychological, and behavioral outcomes: highlights from CALERIE phase 2
Diet – let food be thy medicine…
*Pesco-Mediterranean diet, intermittent fasting may lower heart disease risk Full Text
*Mediterranean diet and endothelial function in patients with coronary heart disease: An analysis of the CORDIOPREV randomized controlled trial Full Text
*Dietary Patterns, Carbohydrates, and Age-Related Eye Diseases Full Text
Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*Exercise Training and Vitamin C Supplementation Affects Ferritin mRNA in Leukocytes without Affecting Prooxidative/Antioxidative Balance in Elderly Women Full Text
*Resistance Exercise, Electrical Muscle Stimulation, and Whole-Body Vibration in Older Adults: Systematic Review and Meta-Analysis of Randomized Controlled Trials Full Text
*The effect of 12-week resistance exercise training on serum levels of cellular aging process parameters in elderly men
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.
Effect of Astaxanthin on the Expression and Activity of Aquaporin-3 in Skin in an In-Vitro Study Full Text
Astaxanthin Suppresses PM2.5-Induced Neuroinflammation by Regulating Akt Phosphorylation in BV-2 Microglial Cells Full Text
Absorbability of Astaxanthin Was Much Lower in Obese Mice Than in Normal Mice
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.
*Novel Bioenhanced Curcumin With Mesalamine for Induction of Clinical and Endoscopic Remission in Mild-to-Moderate Ulcerative Colitis: A Randomized Double-Blind Placebo-controlled Pilot Study
*Oral nano-curcumin on gingival inflammation in patients with gingivitis and mild periodontitis Full Text
Curcumin Attenuates Chronic Unpredictable Mild Stress-Induced Depressive-Like Behaviors via Restoring Changes in Oxidative Stress and the Activation of Nrf2 Signaling Pathway in Rats Full Text
Fisetin – a flavonoid found in highest concentrations in strawberries. Senolytic, anti-inflammatory, anti-cancer, neuro-protective & Sirt1 activator. I take 100mg intermittently.
The molecular mechanism involved in cardioprotection by the dietary flavonoid fisetin as an agonist of PPAR-γ in a murine model of myocardial infarction
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’ve been taking 3mg for years before bed time purely as a sleep aid.
Melatonin and Autophagy in Aging-Related Neurodegenerative Diseases Full Text
Melatonin ameliorates degenerative alterations caused by age in the rat prostate and mitigates high-fat diet damages
Nicotinamide Riboside (NR) – NAD+ precursor.
Re-equilibration of imbalanced NAD metabolism ameliorates the impact of telomere dysfunction Full Text
Can nicotinamide riboside protect against cognitive impairment?
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 reduces endothelial cell apoptosis by regulation of the Nrf2-mediated TLR-4/MyD88/NF-κB pathway in a rat model of atherosclerosis Full Text
Altered paracellular permeability in intestinal cell monolayer challenged with lipopolysaccharide: Modulatory effects of pterostilbene metabolites Full Text
Pterostilbene reduces colonic inflammation by suppressing dendritic cell activation and promoting regulatory T cell development Full Text
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 prevents TNF- α-induced VCAM-1 and ICAM-1 upregulation in endothelial progenitor cells via reduction of NF- κ B activation Full Text
Resveratrol alleviates intestinal mucosal barrier dysfunction in dextran sulfate sodium-induced colitis mice by enhancing autophagy Full Text
Efficacy of resveratrol in the wound healing process by reducing oxidative stress and promoting fibroblast cell proliferation and migration
Spermidine – found in wheat germ and a potent inducer of autophagy, it works in synergy with Resveratrol. I try to eat a few teaspoons of wheat germ every day in my berry & nut breakfast.
Spermidine inhibits neurodegeneration and delays aging via the PINK1-PDR1-dependent mitophagy pathway in C. elegans Full Text
Protective Effects of Spermidine Against Cirrhotic Cardiomyopathy in Bile Duct-Ligated Rats
Spermidine, a caloric restriction mimetic, provides neuroprotection against normal and D-galactose-induced oxidative stress and apoptosis through activation of autophagy in male rats during aging
Other available supplements (in alphabetical order)
Vitamin D Insufficiency Reduces Grip Strength, Grip Endurance and Increases Frailty in Aged C57Bl/6J Mice Full Text
The bright and the dark sides of L-carnitine supplementation: a systematic review Full Text
Quercetin enhances motility in aged and heat-stressed Caenorhabditis elegans nematodes by modulating both HSF-1 activity, and insulin-like and p38-MAPK signalling Full Text
Royal Jelly as an Intelligent Anti-Aging Agent-A Focus on Cognitive Aging and Alzheimer's Disease: A Review Full Text
Apitherapy for Age-Related Skeletal Muscle Dysfunction (Sarcopenia): A Review on the Effects of Royal Jelly, Propolis, and Bee Pollen Full Text
Supplement Combinations
*Effectiveness of the integration of quercetin, turmeric, and N-acetylcysteine in reducing inflammation and pain associated with endometriosis. In vitro and in vivo studies
*An Exploratory Analysis of Changes in Mental Wellbeing Following Curcumin and Fish Oil Supplementation in Middle-Aged and Older Adults Full Text
*Supplementing Glycine and N-acetylcysteine (GlyNAC) in Aging HIV Patients Improves Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Endothelial Dysfunction, Insulin Resistance, Genotoxicity, Strength, and Cognition: Results of an Open-Label Clinical Trial Full Text
Antioxidative Effects of Ascorbic Acid and Astaxanthin on ARPE-19 Cells in an Oxidative Stress Model Full Text
Novel nanoemulsion gel containing triple natural bio-actives combination of curcumin, thymoquinone, and resveratrol improves psoriasis therapy: in vitro and in vivo studies
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 improves cognition of aged mice by promoting cerebral angiogenesis and neurogenesis Full Text
A geroscience perspective on immune resilience and infectious diseases: a potential case for metformin Full Text
Rapamycin (sirolimus) – first drug proven to increase the health & lifespan of mice.
The Target of Rapamycin Signalling Pathway in Ageing and Lifespan Regulation Full Text
The neuromuscular junction is a focal point of mTORC1 signaling in sarcopenia Full Text
Rapamycin maintains NAD +/NADH redox homeostasis in muscle cells Full Text
Other Areas of Interest (in alphabetical order)
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:
Underlying features of epigenetic aging clocks in vivo and in vitro Full Text
Age and life expectancy clocks based on machine learning analysis of mouse frailty Full Text
Promising biomarkers of human aging: In search of a multi-omics panel to understand the aging process from a multidimensional perspective
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:
Epigenetic mutation load is weakly correlated with epigenetic age acceleration Full Text
Heterochromatin: an epigenetic point of view in aging Full Text
Exosomes (small packets of information released by cells)
Extracellular Vesicles: Recent Developments in Aging and Reproductive Diseases Full Text
Aging-Associated Extracellular Vesicles Contain Immune Regulatory microRNAs Alleviating Hyperinflammatory State and Immune Dysfunction in the Elderly Full Text
Exosomes derived from human placenta-derived mesenchymal stem cells improve neurologic function by promoting angiogenesis after spinal cord injury
Lifespan Lengthening Interventions - any intervention which lengthens the lifespan and/or healthspan of model organisms.
Beneficial effects of sappanone A on lifespan and thermotolerance in Caenorhabditis elegans
SUMO promotes longevity and maintains mitochondrial homeostasis during ageing in Caenorhabditis elegans Full Text
Metabolomics profiling reveals the mechanism of caffeic acid in extending lifespan in Drosophila melanogaster
Dietary nitrite extends lifespan and prevents age-related locomotor decline in the fruit fly Full Text
A Bioactive compound Shatavarin IV-mediated longevity as revealed by dietary restriction-induced autophagy in Caenorhabditis elegans
The precursor of PI(3,4,5)P 3 alleviates aging by activating daf-18(Pten) and independent of daf-16 Full Text
Atf-6 Regulates Lifespan through ER-Mitochondrial Calcium Homeostasis Full Text
Microbiome – all the little critters living in and on us have a major influence on our health and potentially our longevity.
Human genetic determinants of the gut microbiome and their associations with health and disease: a phenome-wide association study Full Text.
Microbiomes other than the gut: inflammaging and age-related diseases Full Text
Gut microbiota and old age: Modulating factors and interventions for healthy longevity Full Text
Reviews
Clinical Evidence for Targeting NAD Therapeutically Full Text
Senolytics – not supplements or available now, but the most exciting area of anti-research at the moment.
Clearance of senescent cells during cardiac ischemia-reperfusion injury improves recovery Full Text
Therapeutic Potential of Senolytics in Cardiovascular Disease Full Text
Identification of a novel senomorphic agent, avenanthramide C, via the suppression of the senescence-associated secretory phenotype
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.
Night Cream Containing Melatonin, Carnosine and Helichrysum italicum Extract Helps Reduce Skin Reactivity and Signs of Photodamage: Ex Vivo and Clinical Studies Full Text
Exosomes From Adipose-Derived Stem Cells: The Emerging Roles and Applications in Tissue Regeneration of Plastic and Cosmetic Surgery Full Text
Natural Nrf2 Modulators for Skin Protection 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.
Telomere length: how the length makes a difference Full Text
Telomere length in healthy adults is positively associated with polyunsaturated fatty acids, including arachidonic acid, and negatively with saturated fatty acids
Non-esterified fatty acids and telomere length in older adults: The Cardiovascular Health Study Full Text
Odds & Sods
Δ 9 -Tetrahydrocannabinol promotes oligodendrocyte development and CNS myelination in vivo Full Text
Older people have become younger: physical and cognitive function have improved meaningfully in 30 years
Birth cohort differences in cognitive performance in 75- and 80-year-olds: a comparison of two cohorts over 28 years
Cohort Differences in Maximal Physical Performance: A Comparison of 75- and 80-Year-Old Men and Women Born 28 Years Apart
Microbiome and Longevity: High Abundance of Longevity-Linked Muribaculaceae in the Gut of the Long-Living Rodent Spalax leucodon
Age-associated epigenetic change in chimpanzees and humans
A Link Between the Microbiome, Heat, and Osteoporosis Abstract
Spheroids Promote Vascularization in Tissue Regeneration Abstract
The mitochondrial-targeted peptide SBT-20 ameliorates inflammation and oxidative stress in chronic renal failure Full Text
The Ground Zero of Organismal Life and Aging Full Text
CCL-11 or Eotaxin-1: An Immune Marker for Ageing and Accelerated Ageing in Neuro-Psychiatric Disorders Full Text
Pharmacologically reversible zonation-dependent endothelial cell transcriptomic changes with neurodegenerative disease associations in the aged brain Full Text