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March 2022 Longevity Review
supplements fasting nmn resveratrol rapamycin crispr stem cells reprogramming senolytics
March Madness! There was such an abundance of great studies out in March that my head is still spinning, and made for some nice tricky selection decisions for this month’s Round-Up. For example, there were several interesting senolytic studies including another human result and, just like buses, three exciting reprogramming papers, along with three new lifespan extending drugs for mice. Decisions, decisions - you’ll see what I landed on in the Round-Up.
In addition, there were human trials for NR in Parkinson’s and for Resveratrol in Diabetes, as well as positive retrospective studies for Lithium in dementia and osteoporosis drugs for mortality, to name but a few. There were also a number of observational studies showing that older people these days are younger than ever before - just think what we’ll be able to accomplish when this becomes a stated goal for medicine.
Be sure to go through the supplemental section as there are a number of gems to be found.
Canadian Longevity Association News
We had our first monthly meet-up of the year at the beginning of the month, which will hopefully no longer have any COVID interruptions. Apart from that, there was a fair bit of background work: successfully signed up to Google grants for nonprofits, which will give us all the software and storage space that we need for free and investigated web hosting for our new wordpress website, along with nonprofit bank accounts etc which we will be pulling the trigger on shortly.
Follow us on Twitter @canlongevity in addition to my personal account @ChrisPollyanna1
We are always looking for more help or volunteers, regardless of your skill set or time availability. If you’d be interested in helping us, please fill out this Volunteer Registration Form.
For previous newsletters, you can find them in the Canadian Longevity Association Facebook group, and also my Patreon account, which includes bonus material for supporters.
Canadian Longevity Spotlight
Operating out of Toronto, Acorn Biolabs provides stem cell banking using stem cells from your hair follicles. These are harvested in a mostly pain free non-invasive procedure (I can vouch for that!), and then cryogenically preserved so that you have them available for any future regenerative needs. The idea is that it will be better to use the more youthful cells you have now, than the older cells you will have in the future, as they likely will have more defects. Since February, Acorn’s service is now available to the public at partner clinics in Canada (see the full list here) and will expand availability across North America throughout 2022 - you can sign up to the waitlist here.
March Round-Up:
Further analysis of a previously reported study of the senolytic combo Dasatinib & Quercetin in idiopathic pulmonary fibrosis, showed that it raised the levels of α-Klotho, a geroprotective protein. α-Klotho declines with age, but is important for health and mice which have been engineered to express more α-Klotho live longer.
*Senolytic drugs boost key protective protein Lifespan.io Analysis Full Text
From the Belmonte lab which first reported on partially reprogramming a living animal in 2016, here is a follow up longer term study in naturally aged mice which showed that lengthier treatment was needed to achieve age reversal, though this was more pronounced in the skin and kidney. Make sure to check out the other two papers in the supplemental section as well.
Cellular rejuvenation therapy safely reverses signs of aging in mice Lifespan.io Analysis Abstract
Following on from one of the stand out studies of 2021, which showed GlyNAC supplementation improved cognition and muscle strength in humans, here researchers found that when given to mice it increased their lifespan by 24% compared to controls as well returning various biomarkers to youthful levels. Looking forward to further human studies of this promising compound.
Glutathione Extends Lifespan in Mice by 24% Full Text
Continuing on from some promising results against frailty, Lomecel-B, an allogeneic stem cell formulation, showed a good safety profile in Alzheimer’s and initial indications of some efficacy, though the trial was not powered to find that out.
*Results and insights from a phase I clinical trial of Lomecel-B for Alzheimer's disease Full Text
I cannot say if eating dark chocolate at the time influenced my decision to include this study in the Round-up… However, good news and easily implementable - just make sure that the chocolate is as dark as possible - milk and white chocolate do not count!
*Trial testing cocoa flavanol supplement shows promise for reducing cardiovascular risk Full Text
And finally, an update on the first human gene editing CRISPR trial, which has now passed the one year mark. Although not directly connected to longevity, the successful implementation of CRISPR in humans will be of vital importance to addressing radical life extension in the future.
*First gene-editing treatment injected into the blood reduces toxic protein for up to 1 year Full Text Press Release
Supplemental Section
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.
*Intermittent fasting and changes in Galectin-3: A secondary analysis of a randomized controlled trial of disease-free subjects
Effect of Chronic Moderate Caloric Restriction on the Reproductive Function in Aged Male Wistar Rats Full Text
Caloric Consumption Affects Caloric Restriction in Mice Full Text
Diet – let food be thy medicine…
*Midlife alcohol consumption and later life cognitive impairment: Light drinking is not protective and APOE genotype does not change this relationship Full Text
*Intake and Sources of Dietary Fiber, Inflammation, and Cardiovascular Disease in Older US Adults Full Text
Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*Daily steps and all-cause mortality: a meta-analysis of 15 international cohorts Full Text
*Concurrent Training Increases Serum Brain-Derived Neurotrophic Factor in Older Adults Regardless of the Exercise Frequency Full Text
*Effect of a physical activity and behaviour maintenance programme on functional mobility decline in older adults: the REACT (Retirement in Action) randomised controlled trial Full Text
Non-prescription Supplements (in alphabetical order)
NOTE - the supplements selected below are not exhaustive. They reflect what I thought were the most interesting ones back in 2019, with only a few updates since. I do individual searches for each and simply do not have time to do all others. Additionally, I’ve noticed how a lot of natural supplements affect the same genetic pathways, so I think that there is a lot of overlap and redundancy.
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.
*Randomized controlled trial of astaxanthin impacts on antioxidant status and assisted reproductive technology outcomes in women with polycystic ovarian syndrome
Astaxanthin, a carotenoid antioxidant, pretreatment alleviates cognitive deficits in aircraft noised mice by attenuating inflammatory and oxidative damage to the gut, heart and hippocampus Full Text
Protective capacity of carotenoid trans-astaxanthin in rotenone-induced toxicity in Drosophila melanogaster Full Text
Curcumin – the spice which gives curries their yellow colour. Anti-inflammatory and neuroprotective. Needs to be taken with black pepper (piperine) to improve bioavailability.
*Superior Bioavailability of a Novel Curcumin Formulation in Healthy Humans Under Fasting Conditions Full Text
*Curcumin-Rich Curry Consumption and Neurocognitive Function from 4.5-Year Follow-Up of Community-Dwelling Older Adults (Singapore Longitudinal Ageing Study) Full Text
*Curcumin Enhances Fed-State Muscle Microvascular Perfusion but Not Leg Glucose Uptake in Older Adults Full Text
Fisetin
Improved neuroprotective activity of Fisetin through SNEDDS in ameliorating the behavioral alterations produced in rotenone-induced Parkinson's model
Fisetin alleviates thioacetamide-induced hepatic fibrosis in rats by inhibiting Wnt/β-catenin signaling pathway
Melatonin – a natural hormone produced in the pineal gland, it helps us fall asleep every night, but it has many other functions, including as a mitochondrial antioxidant.
*Melatonin reduces muscle damage, inflammation and oxidative stress induced by exhaustive exercise in people with overweight/obesity
*Evaluation of Melatonin Therapy in Patients with Myocardial Ischemia-Reperfusion Injury: A Systematic Review and Meta-Analysis Full Text
Melatonin induces fat browning by transdifferentiation of white adipocytes and de novo differentiation of mesenchymal stem cells Full Text
Nicotinamide MonoNucleotide (NMN)
Restoring nuclear entry of Sirtuin 2 in oligodendrocyte progenitor cells promotes remyelination during ageing Full Text
Mitochondrial dysregulation occurs early in ALS motor cortex with TDP-43 pathology and suggests maintaining NAD+ balance as a therapeutic strategy Full Text
Antioxidant effect of nicotinamide mononucleotide in tendinopathy Full Text
Nicotinamide Riboside (NR)
*The NADPARK study: A randomized phase I trial of nicotinamide riboside supplementation in Parkinson’s disease Full Text
*Effects of NAD+ precursor supplementation on glucose and lipid metabolism in humans: a meta-analysis Full Text
The role of NAD and NAD precursors on longevity and lifespan modulation in the budding yeast, Saccharomyces cerevisiae Full Text
Pterostilbene
Targeting glycolysis in Th2 cells by pterostilbene attenuates clinical severities in an asthmatic mouse model and IL-4 production in peripheral blood from asthmatic patients
Resveratrol
*Role of resveratrol supplementation in regulation of glucose hemostasis, inflammation and oxidative stress in patients with diabetes mellitus type 2: A randomized, placebo-controlled trial Full Text
Resveratrol in Intestinal Health and Disease: Focusing on Intestinal Barrier Full Text
Resveratrol Blunts Mitochondrial Loss in Slow and Mixed Skeletal Muscle Phenotypes of Non-Human Primates following a Long-Term High Fat/Sugar Diet
Spermidine
The effect of spermidine on autoimmunity and beta cell function in NOD mice Full Text
Effect of spermidine on ameliorating spermatogenic disorders in diabetic mice via regulating glycolysis pathway Full Text
Dynamic Mitochondrial Proteome Under Polyamines Treatment in Cardiac Aging Full Text
Other available supplements (in alphabetical order)
Baicalin improves the functions of granulosa cells and the ovary in aged mice through the mTOR signaling pathway Full Text
Genistein, a tool for geroscience Full Text
The multimodal action of genistein in Alzheimer's and other age-related diseases Full Text
Ginkgo biloba in the Aging Process: A Narrative Review Full Text
Ergothioneine: The “Longevity Vitamin” Improves Locomotor Performances during Aging Full Text
*Study suggests lithium may decrease risk of developing dementia Full Text
Oleanoic Acid Protects Against Cardiac Aging in Mice Abstract
*Intranasal oxytocin modulates the salience network in aging Full Text
PQQ Dietary Supplementation Prevents Alkylating Agent-Induced Ovarian Dysfunction in Mice Full Text
Combinations of Supplements/Treatments
*Impact of high-intensity interval training with or without l-citrulline on physical performance, skeletal muscle, and adipose tissue in obese older adults Full Text
*A Complex of Cirsium japonicum var. maackii (Maxim.) Matisum. and Thymus vulgaris L. Improves Menopausal Symptoms and Supports Healthy Aging in Women
*Effect of Resveratrol Combined with Donepezil Hydrochloride on Inflammatory Factor Level and Cognitive Function Level of Patients with Alzheimer’s Disease Full Text
Pterostilbene in Combination With Mitochondrial Cofactors Improve Mitochondrial Function in Cellular Models of Mitochondrial Diseases Full Text
Prescription Supplements
Metformin
*Metformin: A Narrative Review of Its Potential Benefits for Cardiovascular Disease, Cancer and Dementia Full Text
*Metformin in Fathers Linked to Birth Defects Full Text
*Propensity Score Matching to Determine the Impact of Metformin on All-Cause Mortality in Older Veterans with Diabetes Mellitus
Rapamycin (sirolimus)
*Perfect match: mTOR inhibitors and tuberous sclerosis complex Full Text
*OSBPL2 mutations impair autophagy and lead to hearing loss, potentially remedied by rapamycin Full Text
Activation of Rictor/mTORC2 signaling acts as a pivotal strategy to protect against sensorineural hearing loss Full Text
Miscellaneous Molecules
Oral drug prevents death from COVID-19 in old mice by reversing immune aging Abstract
Dual efficacy of Fasudil at improvement of survival and reinnervation of flap through RhoA/ROCK/PI3K/Akt pathway Full Text
Trimethylamine N-Oxide (TMAO) drives insulin resistance and cognitive deficiencies in a senescence accelerated mouse model Full Text
*Empagliflozin Improves Cognitive Impairment in Frail Older Adults With Type 2 Diabetes and Heart Failure With Preserved Ejection Fraction
J147 Reduces tPA-Induced Brain Hemorrhage in Acute Experimental Stroke in Rats Full Text
Other Areas of Interest (in alphabetical order)
Ageing Clocks & other biomarkers of ageing
*A new monocyte epigenetic clock reveals nonlinear effects of alcohol consumption on biological aging in three independent cohorts (N = 2242) Full Text
*Distinct biological ages of organs and systems identified from a multi-omics study Full Text
*Assessing the causal role of epigenetic clocks in the development of multiple cancers: a Mendelian randomization study Full Text
Utilization of Host and Microbiome Features in Determination of Biological Aging Full Text
Blood Factors or other Heterochronic Transplantation
Molecular hallmarks of heterochronic parabiosis at single-cell resolution
Evaluation of the effect of age of the younger mice on the rejuvenation of the older mice by heterochronic parabiosis Full Text
Aging-associated changes in motor function are ovarian somatic tissue-dependent, but germ cell and estradiol independent in post-reproductive female mice exposed to young ovarian tissue Full Text
Epigenetics & Cellular Reprogramming
Epigenetic MRI: Noninvasive imaging of DNA methylation in the brain Full Text
Multi-omic rejuvenation of naturally aged tissues by a single cycle of transient reprogramming Full Text
Intervertebral Disc Rejuvenation Using Yamanaka Factors Full Text
Exosomes (small packets of information released by cells)
Tonsil mesenchymal stem cells-derived extracellular vesicles prevent submandibular gland dysfunction in ovariectomized rats Full Text
Exosomes in Age-Related Cognitive Decline: Mechanistic Insights and Improving Outcomes Full Text
Recent Advances in the Application of Mesenchymal Stem Cell-Derived Exosomes for Cardiovascular and Neurodegenerative Disease Therapies Full Text
Genetics including CRISPR
*Biological mechanisms of aging predict age-related disease co-occurrence in patients Full Text
AAV-mediated expression of secreted and transmembrane αKlotho isoforms rescues relevant aging hallmarks in senescent SAMP8 mice Full Text
IGF-1 Gene Transfer Modifies Inflammatory Environment and Gene Expression in the Caudate-Putamen of Aged Female Rat Brain
Lifespan Lengthening Interventions
New Candidate Drug Extends Lifespan in Male Mice Full Text
Corylin Shown to Affect Multiple Processes of Aging Full Text
Longevity interventions temporally scale healthspan in Caenorhabditis elegans Full Text
Microbiome
*The Effects of Synbiotics Administration on Stress-Related Parameters in Thai Subjects—A Preliminary Study Full Text
*Gut microbes and muscle function: can probiotics make our muscles stronger? Full Text
*Comparative Analysis of Gut Microbiota in Centenarians and Young People: Impact of Eating Habits and Childhood Living Environment Full Text
Observational Studies
*The association between osteoporosis medications and lowered all-cause mortality after hip or vertebral fracture in older and oldest-old adults: a nationwide population-based study Full Text
*Blood Profile at Age 35 Linked to Subsequent Alzheimer's Dementia Full Text
*'Healthspan' increasing even for people with common chronic conditions Full Text
*Secular trends in prevalent mild cognitive impairment: Data from the Swedish population-based study Good Aging in Skåne Full Text
*Changes in Health Expectancy for Older Adults in Japan: Results from Two Longitudinal Surveys
Opinion/Editorials/Theory
Geroscience-guided repurposing of FDA-approved drugs to target aging: A proposed process and prioritization Full Text
The intervention on aging system: A classification model, the requirement for five novel categories Full Text
A Mechanistic Theory of Development-Aging Continuity in Humans and Other Mammals Full Text
Cellular senescence, rejuvenation and potential immortality Full Text
Cell senescence, rapamycin and hyperfunction theory of aging Full Text
Other Ageing Biology
Different responses to DNA damage determine ageing differences between organs Full Text
Distinct and diverse chromatin proteomes of ageing mouse organs reveal protein signatures that correlate with physiological functions Full Text
Quantitative restoration of immune defense in old animals determined by naive antigen-specific CD8 T-cell numbers Full Text
Regenerative Medicine
A novel prostaglandin E receptor 4 (EP4) small molecule antagonist induces articular cartilage regeneration Full Text
Notochordal Cell-Based Treatment Strategies and Their Potential in Intervertebral Disc Regeneration Full Text
Stem cell–homing hydrogel-based miR-29b-5p delivery promotes cartilage regeneration by suppressing senescence in an osteoarthritis rat model Full Text
Reviews
*Exerkines in health, resilience and disease Full Text
Emerging Role of HDACs in Regeneration and Ageing in the Peripheral Nervous System: Repair Schwann Cells as Pivotal Targets Full Text
Mitochondrial Implications in Cardiovascular Aging and Diseases: The Specific Role of Mitochondrial Dynamics and Shifts Full Text
Senolytics/Senescent Cells
Senolytics: Eliminating Senescent Cells and Alleviating Intervertebral Disc Degeneration Full Text
Attenuation of intrinsic aging of the skin via elimination of senescent dermal fibroblasts with senolytic drugs
Senolytic treatment rescues blunted muscle hypertrophy in old mice Full Text
Identification of gingerenone A as a novel senolytic compound Full Text
Skin & Beauty
*Effectiveness of a Radiofrequency Device for Rejuvenation of Aged Skin at Home: A Randomized Split-Face Clinical Trial Full Text
*Quantified Facial Rejuvenation Utilizing High Intense Focus Ultrasound with Multiple Penetrative Depths Full Text
Combined Treatment of Monopolar and Bipolar Radiofrequency Increases Skin Elasticity by Decreasing the Accumulation of Advanced Glycated End Products in Aged Animal Skin Full Text
Stem Cells
Rejuvenation of Tissue Stem Cells by Intrinsic and Extrinsic Factors Full Text
Primary cilia on muscle stem cells are critical to maintain regenerative capacity and are lost during aging Full Text
Intravenous Transplantation of Human Hair Follicle-Derived Mesenchymal Stem Cells Ameliorates Trabecular Bone Loss in Osteoporotic Mice Full Text
Telomeres
Telomerase deficiency reflects age-associated changes in CD4+ T cells Full Text
CRISPR/Cas: A New Tool in the Research of Telomeres and Telomerase as Well as a Novel Form of Cancer Therapy Full Text
Odds & Sods
*The Effects of Electroencephalogram Feature-Based Transcranial Alternating Current Stimulation on Working Memory and Electrophysiology Full Text
*Influence of Transcranial Direct Current Stimulation Dosage and Associated Therapy on Motor Recovery Post-stroke: A Systematic Review and Meta-Analysis Full Text
Photobiomodulation reduces hippocampal apoptotic cell death and produces a Raman spectroscopic “signature” Full Text
Hibernation slows epigenetic ageing in yellow-bellied marmots Full Text
Unravelling the mystery of parrot longevity Full Text
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***Disclaimer 1 – 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 above 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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