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November 2021 Longevity Review

Posted by Chris Pollyanna , 07 December 2021 · 2,168 views

supplements nmn resveratrol metformin alpha ketogluterate hyperbaric oxygen senolytics

After teasing you for the past two months, I can finally reveal that the Canadian Longevity Association has, since the 18th November, become a federally incorporated non-profit! (Corporation Number 1352499-0)


The background is that in September I was approached by Dmitry Kaminskiy’s Deep Knowledge Group and Franco Cortese at the Aging Analytics Agency, who were interested in setting up a longevity non-profit Canada. Needless to say our interests were aligned, so I agreed to partner up with them and the result is our incorporation. Their involvement certainly sped up this process, as they were able to leverage their legal team to do the grunt work, including the hassle of getting the name approved. So, a big thank you to everyone involved. Now the real work begins!


If you would like to help me grow this new organisation, and have any spare crypto currency, you can donate at Gitcoin Grants. This initiative, which runs until 16th December, uses quadratic funding to multiply your donation by drawing from a matching fund. To be honest, I haven’t gotten my head around the whole crypto currency phenomenon, but if it can result in some funding, then I thought I’d give it a go. I only put a proposal forward after this initiative had already launched, so I was quite surprised today when I saw it had been accepted.


Stay safe!


Follow me on Twitter @ChrisPollyanna1 for the latest updates.


For previous updates, you can find them in the Canadian Longevity Association Facebook group, and also my Patreon account, which includes bonus material for supporters.


Finally, if you are interested in helping grow a Canadian longevity non-profit, then please contact me via the Canadian Longevity Association website.


November Round-Up:


Keto-alphagluterate is a supplement I’ve had my eye on since a mouse study from last year showed considerable healthspan extension, including retention of hair colour. Now there are two studies in humans, the first one claiming a reduction in biological ageing with the second dealing in skin ageing. Although the first one sounds exciting, it should be pointed out that the study was sponsored by a supplement company and didn’t have a placebo control. I eagerly await independent confirmation of these results.
*Alpha-Ketoglutarate Decreases Biological Age in Human Study Full Text
*The study of skin hydration, anti-wrinkles function improvement of anti-aging cream with alpha-ketoglutarate Full Text


Here are two more studies on hyperbaric oxygen therapy, where people breathe in oxygen under higher pressure. This time its effects on skin ageing and gene expression were tested, with positive results. The more that these studies come out, the more I start to believe that there might be something behind this despite my initial scepticism.
*A Clinical Trial of Hyperbaric Oxygen Therapy for Skin Aging Full Text
*Hyperbaric oxygen therapy induces transcriptome changes in elderly: a prospective trial Full Text


Recently, there have been some studies on Metformin which suggested that it might not be good for exercise adaptation and even potentially dangerous for the very old. Here are two studies which refute those claims as well as a third which shows it reduces cognitive impairment for those with type 2 diabetes.
*Skeletal muscle adaptations to exercise are not influenced by metformin treatment in humans: secondary analyses of two randomised, clinical trials
Metformin treatment in old rats and effects on mitochondrial integrity Full Text
*Metformin Alleviates Cognitive Impairment in Long-Term Study Full Text


Here are more results from the AMBAR study, which treated Alzheimer’s by replacing a patient's plasma with albumin. The first results showed a slow down in cognitive deterioration, while these new ones show improved language fluency, processing speed, short term verbal memory, and quality of life. The first clinic providing this treatment has opened in Spain.
*Neuropsychological, neuropsychiatric, and quality-of-life assessments in Alzheimer's disease patients treated with plasma exchange with albumin replacement from the randomized AMBAR study Full Text


With vaccines being all the rage, here’s an interesting study whereby they used vaccination to treat high cholesterol, fatty liver and atherosclerosis in mice. To get a vaccination those conditions would truly be preventative medicine.
Vaccine targeting ANGPTL3 ameliorates dyslipidemia and associated diseases in mouse models of obese dyslipidemia and familial hypercholesterolemia Full Text


Finally, on the topic of vaccination, this retrospective study seems to imply that immunisation against influenza reduces dementia risk:
*Influenza vaccination reduces dementia risk: A systematic review and meta-analysis


Videos to watch:
The 9th Aging Research and Drug Discovery conference took place in September with a stellar lineup of over seventy researchers. The videos have now been posted, so if you’re needing to escape the stress of Christmas, you can lose yourself for quite some time here!
2021 AARD Playlist


2021 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 you need 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.*
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.
Diet composition influences the metabolic benefits of short cycles of very low caloric intake Full Text
The ups and downs of caloric restriction and fasting: from molecular effects to clinical application Full Text
Fitness benefits of dietary restriction Full Text


Diet – let food be thy medicine…
*Crosstalk among intestinal barrier, gut microbiota and serum metabolome after a polyphenol-rich diet in older subjects with “leaky gut”: The MaPLE trial Full Text
*Adding herbs and spices to meals may help lower blood pressure Full Text
*Coffee and tea drinking may be associated with reduced rates of stroke and dementia 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 on Sleep: A Systematic Review and Meta-Analysis Full Text
An exercise “sweet spot” reverses cognitive deficits of aging by growth-hormone-induced neurogenesis Full Text
*Effects of different exercise interventions on heart rate variability and cardiovascular health factors in older adults: a systematic review 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 carotenoid, it has anti-oxidative, anti-inflammatory, anti-cancer, neuro-protective and skin-protective qualities. I take 4 or 8 mg intermittently.
Astaxanthin attenuated hyperuricemia and kidney inflammation by inhibiting uric acid synthesis and the NF-κ B/NLRP3 signaling pathways in potassium oxonate and hypoxanthine-induced hyperuricemia mice Full Text
Natural astaxanthin enhanced antioxidant capacity and improved semen quality through the MAPK/Nrf2 pathway in aging layer breeder roosters Full Text
Anti-inflammatory action of astaxanthin and its use in the treatment of various diseases Full Text


Curcuminthe 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 effect of curcumin as an adjunct in the treatment of chronic periodontitis: A systematic review and meta-analysis Full Text
*Anti-Inflammatory Effects of Curcumin in the Inflammatory Diseases: Status, Limitations and Countermeasures Full Text
Antiviral Therapeutic Potential of Curcumin: An Update Full Text


Fisetina flavonoid found in highest concentrations in strawberries. Senolytic, anti-inflammatory, anti-cancer, neuro-protective & Sirt1 activator. I take 100mg intermittently.
Accumulation of Senescent Neural Cells in Murine Lupus With Depression-Like Behavior Full Text
Fisetin inhibits the proliferation, migration and invasion of pancreatic cancer by targeting PI3K/AKT/mTOR signaling Full Text
Fisetin ameliorates cognitive impairment by activating mitophagy and suppressing neuroinflammation in rats with sepsis-associated encephalopathy 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 Ameliorates Valproic Acid-Induced Neurogenesis Impairment: The Role of Oxidative Stress in Adult Rats Full Text
Protective effect of melatonin against chronic cadmium-induced hepatotoxicity by suppressing oxidative stress, inflammation, and apoptosis in mice Full Text
Therapeutic Effects of Melatonin on Ocular Diseases: Knowledge Map and Perspective Full Text


Nicotinamide MonoNucleotide (NMN) newer NAD+ precursor. I take 250 – 500mg on days I exercise.
Long-term treatment of Nicotinamide mononucleotide improved Age-related Diminished Ovary Reserve through enhancing the mitophagy level of granulosa cells in mice Full Text


Nicotinamide Riboside (NR) NAD+ precursor.
Hepatocyte-specific perturbation of NAD+ biosynthetic pathways in mice induces reversible nonalcoholic steatohepatitis-like phenotypes Full Text
Down-regulation of EPB41L4A-AS1 mediated the brain aging and neurodegenerative diseases via damaging synthesis of NAD+ and ATP 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 Coupled with Physical Exercise Effectively Mitigates Collagen-Induced Articular Synovial by Correcting the PI3K/Akt/NF-κB Signal Pathway
Neuroprotective and Anti-Inflammatory Effect of Pterostilbene Against Cerebral Ischemia/Reperfusion Injury via Suppression of COX-2 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.
*Effect of Resveratrol on Serum Levels of Type II Collagen and Aggrecan in Patients with Knee Osteoarthritis: A Pilot Clinical Study Full Text
Efficiency of resveratrol in the prevention and treatment of age‑related hearing loss Full Text
*Efficacy and safety of vitamin supplements with resveratrol in diabetic macular edema: Long-term results of a comparative study


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.
Protective Role of Spermidine in Colitis and Colon Carcinogenesis


Other available supplements (in alphabetical order)
*Oral L-Arginine (5 g/day) for 14 Days Improves Microcirculatory Function in Healthy Young Women and Healthy and Type 2 Diabetes Mellitus Elderly Women
*The effect of low-dose aspirin on frailty phenotype and frailty index in community-dwelling older adults in the ASPirin in Reducing Events in the Elderly study Full Text
*Aspirin use is associated with increased risk for incident heart failure: a patient-level pooled analysis Full Text
*Dietary Supplementation with Biobran/MGN-3 Increases Innate Resistance and Reduces the Incidence of Influenza-like Illnesses in Elderly Subjects: A Randomized, Double-Blind, Placebo-Controlled Pilot Clinical Trial Full Text
*A Review of the Effects of Collagen Treatment in Clinical Studies Full Text
*Oral vitamin C restores endothelial function during acute inflammation in young and older adults Full Text
*Effects of Vitamin D in Post-Exercise Muscle Recovery. A Systematic Review and Meta-Analysis Full Text


Combinations of Supplements
Astragalus membranaceus treatment combined with caloric restriction may enhance genesis factors and decrease apoptosis in the hippocampus of rats
Protective effects of dietary curcumin and astaxanthin against heat-induced ROS production and skeletal muscle injury in male and female C57BL/6J mice Full Text
Preventing c2c12 muscular cells damage combining magnesium and potassium with vitamin D3 and curcumin Full Text


Prescription Supplements


MetforminAnti-diabetic medication, maintained by many scientists to be a safe longevity enhancing medication.
Metformin treatment of diverse Caenorhabditis species reveals the importance of genetic background in longevity and healthspan extension outcomes Full Text


Rapamycin (sirolimus) – first drug proven to increase the health & lifespan of mice, and the one with the most evidence behind it.
Rapamycin Prevents Stem Cells from Growing Too Big Full Text
Pharmacological inhibition of mTOR attenuates DOCA-salt-induced hypertension and related pathophysiology: regulation of oxidative stress, inflammation and cardiovascular hypertrophy in male rats
Combination Therapy With Rapamycin and Low Dose Imatinib in Pulmonary Hypertension Full Text


Miscellaneous Molecules
Candesartan prevents arteriopathy progression in cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy model Full Text
Gonadal rejuvenation of mice by GDF11
Treatment of age-related visual impairment with a mitochondrial-acting peptide Full Text
PPARα agonist relieves spinal cord injury in rats by activating Nrf2/HO-1 via the Raf-1/MEK/ERK pathway Full Text
New NF-κB Targeting Drug Improves Healthspan in Mice Full Text


Other Areas of Interest (in alphabetical order)


Ageing Clocks & other biomarkers of ageing
*Comparative validation of three DNA methylation algorithms of ageing and a frailty index in relation to mortality: results from the ESTHER cohort study Full Text
*Phenotype correlations reveal the relationships of physiological systems underlying human ageing Full Text
*Urinary peptidomic profiles to address age-related disabilities: a prospective population study Full Text


Blood Factors or other Heterochronic Transplantation
Using Young Stem Cells to Restore Old Stem Cells Full Text
*Efficacy of Cord Blood Cell Therapy for Hutchinson–Gilford Progeria Syndrome—A Case Report Full Text


Exosomes (small packets of information released by cells)
Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Accelerate Functional Recovery After Spinal Cord Injury by Promoting the Phagocytosis of Macrophages to Clean Myelin Debris Full Text
Mesenchymal stromal cell-derived small extracellular vesicles promote neurological recovery and brain remodeling after distal middle cerebral artery occlusion in aged rats Full Text
Engineered extracellular vesicles derived from primary M2 macrophages with anti-inflammatory and neuroprotective properties for the treatment of spinal cord injury Full Text


Genetics including CRISPR
LARP7 ameliorates cellular senescence and aging by allosterically enhancing SIRT1 deacetylase activity Full Text
Genomic expansion of Aldh1a1 protects beavers against high metabolic aldehydes from lipid oxidation Full Text
Cisd2 slows down liver aging and attenuates age-related metabolic dysfunction in male mice Full Text


Lifespan Lengthening Interventions
Bifidobacterium Adolescentis Improves Lifespan in Animals Abstract
Growth hormone receptor gene disruption in mature-adult mice improves male insulin sensitivity and extends female lifespan Full Text
Daily ingestion of Akkermansia mucciniphila for one month promotes healthy aging and increases lifespan in old female mice
Naringenin prolongs lifespan and delays aging mediated by IIS and MAPK in Caenorhabditis elegans
Mild Muscle Mitochondrial Fusion Distress Extends Drosophila Lifespan through an Early and Systemic Metabolome Reorganization Full Text


A fiber-deprived diet causes cognitive impairment and hippocampal microglia-mediated synaptic loss through the gut microbiota and metabolites Full Text
Research in mice shows how diet alters immune system function through a gut microbe
Exercise increases the body’s own ‘cannabis-like' substance which reduces chronic inflammation Full Text


Observational Studies
*Adherence to the Mediterranean diet assessed by a novel dietary biomarker score and mortality in older adults: the InCHIANTI cohort study Full Text
*Poor sleep linked to feeling older and worse outlook on ageing, which can impact health Full Text
*Association of glycated hemoglobin A1c levels with cardiovascular outcomes in the general population: results from the BiomarCaRE (Biomarker for Cardiovascular Risk Assessment in Europe) consortium Full Text


Senescence as a trade-off between successful land colonisation and longevity: critical review and analysis of a hypothesis Full Text
New Directions in Research on Aging Full Text
Medawar and Hamilton on the selective forces in the evolution of ageing Full Text


Other Ageing Biology
Evolution of natural lifespan variation and molecular strategies of extended lifespan Full Text
Small interfering RNA-induced silencing lncRNA PVT1 inhibits atherosclerosis via inactivating the MAPK/NF-κB pathway Full Text
Loss of toll-like receptor 4 ameliorates cardiovascular dysfunction in aged mice Full Text


*Nutrition, Physical Activity, and Other Lifestyle Factors in the Prevention of Cognitive Decline and Dementia Full Text
*The aging venous system: from varicosities to vascular cognitive impairment Full Text
Potential Nutrients from Natural and Synthetic Sources Targeting Inflammaging—A Review of Literature, Clinical Data and Patents Full Text


Senolytics/Senescent Cells
Deleting dysfunctional cells alleviates diabetes Abstract
Skeletal muscle aging, cellular senescence, and senotherapeutics: Current knowledge and future directions Full Text
Senolytic Therapy Shows Potential for Stroke Recovery Full Text


Skin & Beauty
*Transcriptomic analysis of human skin wound healing and rejuvenation following ablative fractional laser treatment Full Text
*Treatment of periorbital wrinkles using thermo-mechanical fractional injury therapy versus fractional non-ablative 1565 nm laser: A comparative prospective, randomized, double-arm, controlled study
Nicotinamide Alleviates Skin Aging in Cellular Study Full Text


Stem Cells
Building a Universal Immunotherapy for Cancer Full Text
Human adipose-derived stromal/stem cells expressing doublecortin improve cartilage repair in rabbits and monkeys Full Text
Comparison of Antiobesity Effects of Adipose-Derived Stromal/Stem Cells from Different Sources in a Natural Aging Model Full Text


Systemic Administration of Telomerase RNA Reverses Vascular Senescence and Extends Lifespan in Progeria Mice
Stress and Telomere Shortening: Insights from Cellular Mechanisms Full Text
Homologous recombination-mediated irreversible genome damage underlies telomere-induced senescence Full Text


Odds & Sods
*Morning exposure to deep red light improves declining eyesight Full Text
*The effect of smiling on the perceived age of male and female faces across the lifespan Full Text
Explaining inter-lab variance in C. elegans N2 lifespan: Making a case for standardized reporting to enhance reproducibility Full Text
Concurrent evolution of anti-aging gene duplications and cellular phenotypes in long-lived turtles Full Text
Moxibustion may delay the aging process of Wistar rats by regulating intestinal microbiota Full Text
Cellular resilience and baboon aging Full Text

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