May 2022 Longevity Review

Another month, another step towards our longevity future, with plenty of advances to showcase. In the Round-Up you will find a human trial of a new supplement, a novel combination of drugs, gene therapy and more. There are also some more human results with Glucosamine, NMN, Metformin and others. Unfortunately, there was a disappointing human trial result for Spermidine, but hopefully that was due to an insufficient dose for too short a time period as the authors speculated. And, besides featuring in the Round-Up, there were also so many papers this month on Urolithin A that it has received its own subsection.

CLA News

This past month the CLA almost opened a non-profit account, but at the last minute found out we need to fulfill a couple more requirements. Hopefully that will be sorted soon so that we will be able to accept donations.

We have also selected a new Wordpress managed web-host, and are in the process of transferring the current site over. (Shout out to Bryan for all his help!) With the new Wordpress site we will be able to expand it much easier - to which point, we’ll be needing more writers. So, if you have an interest in writing about longevity, or would just like to help us out with the new site, please get in touch!

Even if you don’t fancy writing for us, 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.

Follow us on Twitter @canlongevity in addition to my personal account @ChrisPollyanna1

Canadian Longevity Association YouTube Channel - where you will find talkthroughs of these newsletters.

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

Lifespan Society

Based in British Columbia, the Lifespan Society is another Canadian longevity non-profit, focusing more on cryogenics. If you’re at all interested in cryogenics, or just curious about it, then this is an organisation you need to join. They also have some good discounts for members which are worth more than the cost of membership!

If you know of any other Canadian longevity companies or organisations that I should feature, please let me know!

May 2022 Round-Up:

A human trial of a new (& expensive) supplement, Urolithin A, shows multiple muscular benefits and might be useful against sarcopenia. I’m hoping I’m one of the lucky people whose gut microbiome naturally produces Urolithin A after eating walnuts or pomegranate!
*Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults Full Text

Here, a combination of acarbose, phenylbutyrate and rapamycin had a greater effect on mouse health and lifespan than any of the individual drugs on their own - see, it’s all about the combinations!
Drug Cocktail Delays Aging in Mice Full Text

There have been numerous instances of young blood, plasma or stem cells given to older animals producing rejuvenatory effects. Here, young cerebrospinal fluid joins in the fun, improving memory and the production of oligodendrocytes, which protect neurons, in old mice.
Young Cerebrospinal Fluid Improves Memory in Mice Abstract

Here, two different gene therapies were used to extend mouse lifespan, including one which extended their telomeres. The significance is that normal aged mice were used, so it has applicability to humans.
Using an Endemic Virus as a Gene Therapy for Life Extension Full Text

In this last paper, researchers developed a means of orally delivering GDF11, a signalling molecule which rejuvenates stem cells and which some biohackers are already using to promising effect (check out GDF11Rejuvenation.com). However, up until now, they've had to use daily injections. If injections could be replaced by an oral dose, that would make it a lot more palatable.
Dietary intake of GDF11 delays the onset of several biomarkers of aging in male mice through anti-oxidant system via Smad2/3 pathway Full Text

Supplemental Section

Lifestyle
*Impact of modifiable healthy lifestyle adoption on lifetime gain from middle to older age Full Text
*Age- and sex-specific effects of a long-term lifestyle intervention on body weight and cardiometabolic health markers in adults with prediabetes: results from the diabetes prevention study PREVIEW Full Text
*Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome in Women: Effects of Lifestyle Modifications Full Text

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.
Caloric Restriction, Feeding Times Lengthen Mouse Lifespan Abstract
Intermittent methionine restriction reduces IGF-1 levels and produces similar healthspan benefits to continuous methionine restriction Full Text
*Association of Daily Eating Duration and Day-To-Day Variability in the Timing of Eating With Fatal Cancer Risk in Older Men Full Text

Diet – let food be thy medicine…
*Dementia Risk Tied to Antioxidant Levels Abstract
Dietary Blueberries Improve Vascular Inflammation and Alter the Composition of the Gut Microbiome in Aged Mice Full Text
*Chronic Consumption of Cranberries (Vaccinium macrocarpon) for 12 Weeks Improves Episodic Memory and Regional Brain Perfusion in Healthy Older Adults: A Randomised, Placebo-Controlled, Parallel-Groups Feasibility Study Full Text

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*Weights can be weapons in battle against obesity Full Text
*Different exercise training modalities similarly improve heart rate variability in sedentary middle-aged adults: the FIT-AGEING randomized controlled trial Full Text
*Multicomponent intervention to prevent mobility disability in frail older adults: randomised controlled trial (SPRINTT project) 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.
*Astaxanthin Influence on Health Outcomes of Adults at Risk of Metabolic Syndrome: A Systematic Review and Meta-Analysis Full Text
Astaxanthin improves the development of the follicles and oocytes through alleviating oxidative stress induced by BPA in cultured follicles Full Text
Recent Advances and the Mechanism of Astaxanthin in Ophthalmological Diseases 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.
*Curcumin: Useful add-on for Rheumatic Diseases? Full Text
*The Effect of Curcumin on Idiopathic Parkinson Disease: A Clinical and Skin Biopsy Study Full Text
*The effect of curcumin supplementation on delayed-onset muscle soreness, inflammation, muscle strength, and joint flexibility: A systematic review and dose-response meta-analysis of randomized controlled trials

Fisetin
Fisetin Supplementation Improves Age-Related Vascular Endothelial Function by Suppressing Cellular Senescence and Mitochondrial Oxidative Stress
Fisetin: An Integrated Approach to Identify a Strategy Promoting Osteogenesis Full Text

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.
*Assessment of the Therapeutic Potential of Melatonin for the Treatment of Osteoporosis Through a Narrative Review of Its Signaling and Preclinical and Clinical Studies Full Text
*Three months of melatonin treatment reduces insulin sensitivity in patients with type 2 diabetes - a randomized placebo-controlled crossover trial
*Effects of melatonin prolonged-release on both sleep and motor symptoms in Parkinson’s disease: a preliminary evidence Full Text

Nicotinamide MonoNucleotide (NMN)
*NMN Human Trial Results Published Full Text
Nicotinamide Mononucleotide Administration Amends Protein Acetylome of Aged Mouse Liver Full Text
Nicotinamide Mononucleotide Alleviates Cardiomyopathy Phenotypes Caused by Short-Chain Enoyl-Coa Hydratase 1 Deficiency Full Text (April 2022)

Nicotinamide Riboside (NR)
NAD+ Precursors Repair Mitochondrial Function in Diabetes and Prevent Experimental Diabetic Neuropathy Full Text & NMN (April 2022)
Acute Treatment with Nicotinamide Riboside Chloride Reduces Hippocampal Damage and Preserves the Cognitive Function of Mice with Ischemic Injury
Nicotinamide riboside supplementation exerts an anti-obesity effect and prevents inflammation and fibrosis in white adipose tissue of female diet-induced obesity mice

Pterostilbene
Triad3A-Dependent TLR4 Ubiquitination and Degradation Contributes to the Anti-Inflammatory Effects of Pterostilbene on Vascular Dementia
Based on Network Pharmacology and Gut Microbiota Analysis to Investigate the Mechanism of the Laxative Effect of Pterostilbene on Loperamide-Induced Slow Transit Constipation in Mice Full Text

Resveratrol
Interactions of resveratrol and its metabolites (resveratrol-3-sulfate, resveratrol-3-glucuronide, and dihydroresveratrol) with serum albumin, cytochrome P450 enzymes, and OATP transporters Full Text
Involvement of the SIRT1/PGC-1α Signaling Pathway in Noise-Induced Hidden Hearing Loss Full Text
*Effect of resveratrol supplementation on hepatic steatosis and cardiovascular indices in overweight subjects with type 2 diabetes: a double-blind, randomized controlled trial Full Text

Spermidine
*Spermidine Human Trial Results Fail to Impress Full Text
Spermidine Ameliorates Nonalcoholic Steatohepatitis through Thyroid Hormone-Responsive Protein Signaling and the Gut Microbiota-Mediated Metabolism of Bile Acids
Investigating the Role of Spermidine in a Model System of Alzheimer’s Disease Using Correlative Microscopy and Super-resolution Techniques Full Text

Urolithin A
Urolithin A attenuates auditory cell senescence by activating mitophagy Full Text
Paclitaxel and Urolithin A Prevent Histamine-Induced Neurovascular Breakdown Alike, in an Ex Vivo Rat Eye Model
Gut Metabolite Urolithin A Inhibits Osteoclastogenesis and Senile Osteoporosis by Enhancing the Autophagy Capacity of Bone Marrow Macrophages Full Text

Other available supplements (in alphabetical order)
*Long-term low-dose acetylsalicylic use shows protective potential for the development of both vascular dementia and Alzheimer’s disease in patients with coronary heart disease but not in other individuals from the general population: results from two large cohort studies Full Text
*Strongly increased risk of gastric and duodenal ulcers among new users of low-dose aspirin: Results from two large cohorts with new-user design Full Text
Berberine exerts protective effects on cardiac senescence by regulating the Klotho/SIRT1 signaling pathway Full Text
Caffeic Acid Alleviates Memory and Hippocampal Neurogenesis Deficits in Aging Rats Induced by D-Galactose Full Text
Coffee Polyphenol, Chlorogenic Acid, Suppresses Brain Aging and Its Effects Are Enhanced by Milk Fat Globule Membrane Components Full Text
*Vitamin D supplementation is associated with slower epigenetic aging Full Text
Ginger for Healthy Ageing: A Systematic Review on Current Evidence of Its Antioxidant, Anti-Inflammatory, and Anticancer Properties Full Text
Long-term consumption of green tea EGCG enhances murine healthspan by mitigating multiple aspects of cellular senescence in mitotic and post-mitotic tissues, gut dysbiosis, and immunosenescence
*Prescription-grade crystalline glucosamine sulfate as an add-on therapy to conventional treatments in erosive osteoarthritis of the hand: results from a 6-month observational retrospective study Full Text
*Short-term L-Citrulline supplementation and macro- and micro-vascular function in old adults
*The Association Between Selenium, Selenoprotein P (SEPP1), Fluid Intelligence, and Exercise in the UK Biobank Cohort Full Text

Combinations of Supplements
A Novel Herbal Extract Blend Product Prevents Particulate Matters-Induced Inflammation by Improving Gut Microbiota and Maintaining the Integrity of the Intestinal Barrier Full Text
Combination of natural polyphenols with a precursor of NAD+ and a TLR2/6 ligand lipopeptide protects mice against lethal γ radiation Full Text

Prescription Supplements

Metformin
*Effects of chronic metformin treatment on training adaptations in men and women with hyperglycemia: A prospective study Full Text
*Metformin: Is it a drug for all reasons and diseases? Full Text
*Effects of Long-term Metformin and Lifestyle Interventions on Cardiovascular Events in the Diabetes Prevention Program and Its Outcome Study Full Text

Rapamycin (sirolimus)
Fighting Alzheimer’s Disease with Increased Autophagy Abstract
*Sirolimus as a promising drug therapy for blue rubber bleb nevus syndrome: Two-case report Full Text
Chronic rapamycin treatment decreases hepatic IL-6 protein but increases autophagy markers as a protective effect against the overtraining-induced tissue damage

Miscellaneous Molecules
Effect of Humanin G (HNG) on inflammation in age-related macular degeneration (AMD) Full Text
Mitochondria-derived peptides in aging and healthspan Full Text
GLP-1 Analog Alleviated Cognitive Dysfunction in Aged Rats Anaesthetized with Sevoflurane Full Text liraglutide
HIV drug could combat middle-aged memory loss, study suggests Abstract

Other Areas of Interest (in alphabetical order)

Ageing Clocks & other biomarkers of ageing
*A Model for Estimating Biological Age From Physiological Biomarkers of Healthy Aging: Cross-sectional Study Full Text
*Urinary Biomarkers of Oxidative Stress in Aging: Implications for Prediction of Accelerated Biological Age in Prospective Cohort Studies Full Text
*Integrative analysis of clinical and epigenetic biomarkers of mortality Full Text

Blood Factors or other Heterochronic Transplantation
Parabiosis Improves Endothelial Dysfunction in Aged Female Mice
Heterochronic parabiosis induces stem cell revitalization and systemic rejuvenation across aged tissues

Epigenetics & Cellular Reprogramming
The relationship between epigenetic age and the hallmarks of ageing in human cells Full Text
*DNA methylation signature of chronic low-grade inflammation and its role in cardio-respiratory diseases Full Text
Reprogramming neurons for regeneration: The fountain of youth Full Text

Exosomes (small packets of information released by cells)
The Protective Effects of Osteocyte-Derived Extracellular Vesicles Against Alzheimer's Disease Diminished with Aging Full Text
Adult mouse kidney stem cell-derived exosomes navigate nephron repair and regeneration in aged mice
Extracellular Vesicles from iPSC derived Muscle Progenitor Cells Rejuvenate the Dysfunctional Muscle Stem Cells during Aging

Genetics including CRISPR
*Genome-wide and phenome-wide analysis of ideal cardiovascular health in the VA Million Veteran Program Full Text
How Important Are Genes to Achieve Longevity? Full Text
The secret to a longer lifespan? Gene regulation holds a clue Abstract

Lifespan Lengthening Interventions
FOXM1 Induction Extends Lifespan in Mice Abstract
Chloroquine Increases Lifespan in Male Mice Full Text
Oridonin Delays Aging Through the AKT Signaling Pathway Full Text
Ingestion of single guide RNAs induces gene overexpression and extends lifespan in C. elegans via CRISPR activation Full Text
The Role of Mitochondrial Antioxidants in Longevity Full Text
Remofuscin induces xenobiotic detoxification via a lysosome-to-nucleus signaling pathway to extend the Caenorhabditis elegans lifespan Full Text

Microbiome
*Changes in Gut Microbiome Composition with Healthy Aging in Humans: Links to Vascular Endothelial Function
Gut microbiome mediates the protective effects of exercise after myocardial infarction Full Text
Gut Microbiota Dysbiosis Induced by Decreasing Endogenous Melatonin Mediates the Pathogenesis of Alzheimer’s Disease and Obesity Full Text

Observational Studies
*Lifetime exposure to smoking, epigenetic aging, and morbidity and mortality in older adults Full Text
*Eveningness is associated with sedentary behavior and increased 10-year risk of cardiovascular disease: the SCAPIS pilot cohort Full Text
*Healthy Choices in Midlife Predict Survival to Age 85 in Women: The Tromsø Study 1979–2019 Full Text (April 2022)

Opinion/Editorials/Theory
*Association Between Dietary Inflammatory Index and S-Klotho Plasma Levels in Middle-Aged and Elderly People Full Text
*The effect of ageing on fat infiltration of thigh and paraspinal muscles in men Full Text
*The relationship between nutritional status at the time of stroke on adverse outcomes: a systematic review and meta-analysis of prospective cohort studies

Opinion/Theory
Selection on age-specific survival: Constant versus fluctuating environment Full Text
An integrative approach to dietary balance across the life course Full Text (April 2022)
Hallmarks of cancer and hallmarks of aging Full Text

Other Ageing Biology
Life after death for the human eye: Vision scientists revive light-sensing cells in organ donor eyes Abstract
Researchers overcome a major hurdle to reverse hearing loss due to aging Abstract
Researchers identify novel cellular process that help us understand the mechanisms of aging-related diseases Full Text

Regenerative Medicine
Cardiac progenitor cells generate healthy tissue after a heart attack Full Text
Innovative Cell and Platelet Rich Plasma Therapies for Diabetic Foot Ulcer Treatment: The Allogeneic Approach Full Text
Advances in Regenerative Sports Medicine Research Full Text

Reproductive Health
Fecal microbiota transplantation from young donor mice improves ovarian function in aged mice Full Text
Low NAD+ Levels Are Associated With a Decline of Spermatogenesis in Transgenic ANDY and Aging Mice Full Text
*Resveratrol Treatment Induces Mito-miRNome Modification in Follicular Fluid from Aged Women with a Poor Prognosis for In Vitro Fertilization Cycle Full Text

Reviews
Antiaging agents: safe interventions to slow aging and healthy life span extension Full Text
Mitochondrial transfer/transplantation: an emerging therapeutic approach for multiple diseases Full Text
Role of low-dose radiation in senescence and aging: A beneficial perspective Full Text

Senolytics/Senescent Cells
Senolytic Interventions Ameliorate Radiation Damage in Mice Full Text
Analysis of senescence in gingival tissues and gingival fibroblast cultures Full Text
The multifaceted role of the SASP in atherosclerosis: from mechanisms to therapeutic opportunities Full Text

Skin & Beauty
*Ozone Therapy for Dermatological Conditions: A Systematic Review Full Text
Endothelial Cell-Derived Extracellular Vesicles Target TLR4 via miRNA-326-3p to Regulate Skin Fibroblasts Senescence Full Text
Valsartan and sacubitril combination treatment enhances collagen production in older adult human skin cells

Stem Cells
*Nutrition and stem cell integrity in aging Full Text
Mesenchymal stem cell homing to improve therapeutic efficacy in liver disease Full Text
Treatment of Pelvic Organ Prolapse by the Downregulation of the Expression of Mitofusin 2 in Uterosacral Ligament Tissue via Mesenchymal Stem Cells Full Text

Telomeres
*Relative Telomere Length Is Associated With Age-Related Macular Degeneration in Women Full Text
*How social/environmental determinants and inflammation affect salivary telomere length among middle-older adults in the health and retirement study Full Text
*Association of Dietary Magnesium Intake With Leukocyte Telomere Length in United States Middle-Aged and Elderly Adults Full Text

Odds & Sods
*Beneficial Effect of High-Frequency Repetitive Transcranial Magnetic Stimulation for the Verbal Memory and Default Mode Network in Healthy Older Adults Full Text
*Hyperbaric oxygen therapy for healthy aging: From mechanisms to therapeutics Full Text
Limited accumulation of high-frequency somatic mutations in a 1,700-year-old Osmanthus fragrans tree
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***Disclaimer 1 – 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 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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