June 2022 Longevity Review

Welcome to a slightly truncated Longevity Review. As I started putting this together, I came down with COVID for the first time, which has set me back several days. I’ve recently been feeling that I’m falling behind where I want to be with the CLA and want to change that, so I will keep the written portions of this review brief and let the studies speak for themselves.

(Fortunately, I was triple vaccinated, so my illness was not that severe, but it was still the worst illness I’ve experienced for at least a decade!)

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Canadian Longevity Spotlight

LessDeath

Mark Hamalainen, a Canadian living in California, has set up a non-profit aimed at expanding the number of people working in the longevity field. Their first summer camp will be held on 21-23 July, and although it is fully subscribed, you can join the waiting list for the next one.

June 2022 Round-Up:

Age-related macular degeneration (AMD) is one of the leading causes of vision loss, and there have been attempts to use combinations of supplements to help ward it off. One previous combination was effective in reducing progression, but unfortunately led to greater lung cancer risk. In this new study beta-carotene was replaced with lutein and zeaxanthin, which not only removed the risk of lung cancer, but further reduced the risk of progression compared to the original formulation.
*Benefit of supplements for slowing age-related macular degeneration Full Text

Waning fertility is one of the earliest manifestations of ageing, and one of the greatest unmet medical needs. Here, a couple of anti-fibrotic drugs (pirfenidone and BGP-15) restored ovulation in reproductively old mice.
Female reproductive life span is extended by targeted removal of fibrotic collagen from the mouse ovary Full Text

Excited to see that trials have started for treating hearing loss, especially speech in noise, which is one of the most common hearing related complaints. A bit further digging showed that they have already moved on to Phase 2 trials according to this April press release.
*A neurotrophic approach to treating hearing loss: Translation from animal models to clinical proof-of-concept Full Text

Here, a probiotic was able to induce improved physical performance in heart failure patients, which if it pans out in larger trials could be a simple method of treating sarcopenia.
*A multistrain probiotic reduces sarcopenia by modulating Wnt signaling biomarkers in patients with chronic heart failure

Beyond caloric restriction, the first evidence for lifespan extension was shown back in the 1990s by the knock-out of some non-essential genes in c.elegans. Here researchers have gone in the opposite direction by increasing the expression of essential genes, finding that a greater percentage of them had an impact on lifespan. This could open up a very fruitful avenue for future research.
Evidence that conserved essential genes are enriched for pro-longevity factors Full Text

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.
*Could the ketogenic diet induce a shift in thyroid function and support a metabolic advantage in healthy participants? A pilot randomized-controlled-crossover trial Full Text
*Higher protein intake while dieting leads to healthier eating Full Text
Inflammaging is driven by upregulation of innate immune receptors and systemic interferon signaling and is ameliorated by dietary restriction Full Text

Diet – let food be thy medicine…
*Association of Diet Quality With Longevity and Successful Aging in Israeli Adults 65 Years or Older Full Text
*Association between Dietary Inflammatory Index and serum Klotho concentration among adults in the United States Full Text
*Impact of fish consumption on all-cause mortality in older people with and without dementia: a community-based cohort study Full Text

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*Blood Flow Restriction Training for the Intervention of Sarcopenia: Current Stage and Future Perspective Full Text
*Nitric oxide, aging and aerobic exercise: Sedentary individuals to Master's athletes Full Text
*High-intensity interval training modulates inflammatory response in Parkinson’s disease 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.

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 - The Nutraceutical With Pleiotropic Effects? Which Cardiometabolic Subjects Might Benefit the Most? Full Text
Curcumin improves D-galactose and normal-aging associated memory impairment in mice: In vivo and in silico-based studies Full Text & Astaxanthin
*Three months of combination therapy with nano-curcumin reduces the inflammation and lipoprotein (a) in type 2 diabetic patients with mild to moderate coronary artery disease: Evidence of a randomized, double-blinded, placebo-controlled clinical trial

Fisetin
Discovering the Effects of Fisetin on NF-κB/NLRP-3/NRF-2 Molecular Pathways in a Mouse Model of Vascular Dementia Induced by Repeated Bilateral Carotid Occlusion Full Text
Fisetin Attenuated Oxidative Stress-Induced Cellular Damage in ARPE-19 Human Retinal Pigment Epithelial Cells Through Nrf2-Mediated Activation of Heme Oxygenase-1 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.
The Prospective Application of Melatonin in Treating Epigenetic Dysfunctional Diseases Full Text (May 2022)
Melatonin as an Anti-Aging Therapy for Age-Related Cardiovascular and Neurodegenerative Diseases Full Text
Melatonin prevents age-related hearing loss in the murine experimental model Full Text

Nicotinamide MonoNucleotide (NMN)
Nicotinamide mononucleotide supplementation protects the intestinal function in aging mice and d-galactose induced senescent cells
Nicotinamide Mononucleotide Administration Restores Redox Homeostasis via the Sirt3–Nrf2 Axis and Protects Aged Mice from Oxidative Stress-Induced Liver Injury

Nicotinamide Riboside (NR)
A reduced form of nicotinamide riboside protects the cochlea against aminoglycoside-induced ototoxicity by SIRT1 activation Full Text (May 2022)
Nicotinamide Riboside Supplementation to Suckling Male Mice Improves Lipid and Energy Metabolism in Skeletal Muscle and Liver in Adulthood Full Text
Nicotinamide riboside and caffeine partially restore diminished NAD availability but not altered energy metabolism in Alzheimer's disease Full Text

Pterostilbene
Pterostilbene, a resveratrol derivative, improves ectopic lipid deposition in the kidneys of mice induced by a high-fat diet Full Text

Resveratrol
*Effects of Resveratrol on Metabolic Indicators in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis Full Text
Resveratrol as a Promising Polyphenol in Age-Associated Cardiac Alterations Full Text
*Resveratrol decreases local inflammatory markers and systemic endotoxin in patients with aggressive periodontitis Full Text

Other available supplements (in alphabetical order)
α-Ketoglutaric acid ameliorates hyperglycemia in diabetes by inhibiting hepatic gluconeogenesis via serpina1e signaling Full Text (May 2022)
β-Hydroxybutyrate in Cardiovascular Diseases : A Minor Metabolite of Great Expectations Full Text
*DHA status influences effects of B-vitamin supplementation on cognitive ageing: a post-hoc analysis of the B-proof trial Full Text
*About 3 grams a day of omega-3 fatty acids may lower blood pressure, more research needed Full Text

Combinations of Supplements
Curcumin and metformin synergistically modulate peripheral and central immune mechanisms of pain Full Text
Combined Administration of Curcumin and Chondroitin Sulfate Alleviates Cartilage Injury and Inflammation via NF-κB Pathway in Knee Osteoarthritis Rats Full Text (May 2022)
Metformin, Rapamycin, or Nicotinamide Mononucleotide Pretreatment Attenuate Cognitive Impairment After Cerebral Hypoperfusion by Inhibiting Microglial Phagocytosis Full Text
Synergistic Anti-Inflammatory Activity of Ginger and Turmeric Extracts in Inhibiting Lipopolysaccharide and Interferon-γ-Induced Proinflammatory Mediators Full Text

Prescription Supplements

Metformin
*Effects of Metformin on Renal Function, Cardiac Function, and Inflammatory Response in Diabetic Nephropathy and Its Protective Mechanism Full Text
Metformin Ameliorates Senescence of Adipose-Derived Mesenchymal Stem Cells and Attenuates Osteoarthritis Progression via the AMPK-Dependent Autophagy Pathway Full Text

Rapamycin (sirolimus)
mTOR Attenuation with Rapamycin Reverses Neurovascular Uncoupling and Memory Deficits in Mice Modeling Alzheimer's Disease Full Text (May 2022)
Rapamycin Dampens Inflammatory Properties of Bone Marrow ILC2s in IL-33-Induced Eosinophilic Airway Inflammation Full Text

Miscellaneous Molecules
SS-31, a Mitochondria-Targeting Peptide, Ameliorates Kidney Disease Full Text
Neuroprotective effects of Canagliflozin: Lessons from aged genetically diverse UM-HET3 mice Full Text
Pleiotropic activation of endothelial function by angiotensin II receptor blockers is crucial to their protective anti-vascular remodeling effects Full Text

Other Areas of Interest (in alphabetical order)

Ageing Clocks & other biomarkers of ageing
*Cardiovascular health and four epigenetic clocks Full Text
*Predicting mortality in The Irish Longitudinal Study on Ageing (TILDA): development of a four-year index and comparison with international measures Full Text
Epigenetic Clocks for Mice Based on Age-Associated Regions That are Conserved Between Mouse Strains and Human Full Text

Blood Factors or other Heterochronic Transplantation
Reciprocal blood exchange in heterochronic parabionts has a deleterious effect on the lifespan of young animals without a positive effect for old animals

Epigenetics & Cellular Reprogramming
Epigenetic aging: Biological age prediction and informing a mechanistic theory of aging Full Text
Counteracting aged DNA methylation states to combat ageing and age-related diseases Full Text
*Dynamic epigenetic age mosaicism in the human atherosclerotic artery Full Text

Exosomes (small packets of information released by cells)
Exercise increases the release of NAMPT in extracellular vesicles and alters NAD+ activity in recipient cells Full Text
Stem Cell-derived Exosomal MicroRNA as Therapy for Vascular Age-related Diseases Full Text
Delivery of engineered extracellular vesicles with miR-29b editing system for muscle atrophy therapy Full Text

Genetics including CRISPR
*Cellular secrets of aging unlocked by researchers Full Text
Genetic trade-offs between complex diseases and longevity Full Text
Identification of healthspan-promoting genes in Caenorhabditis elegans based on a human GWAS study Full Text

Lifespan Lengthening Interventions
Molecular mechanisms of exceptional lifespan increase of Drosophila melanogaster with different genotypes after combinations of pro-longevity interventions Full Text
Lysosome lipid signalling from the periphery to neurons regulates longevity Full Text
The PICLS high-throughput screening method for agents extending cellular longevity identifies 2,5-anhydro-D-mannitol as novel anti-aging compound Full Text

Microbiome
*Lager beer, whether it contains alcohol or not, could help men's gut microbes Abstract
Age-associated gut microbiota impairs hippocampus-dependent memory in a vagus-dependent manner Full Text

Observational Studies
*The younger we feel, the better we rehabilitate, research shows Full Text
*Stress accelerates immune aging, study finds Full Text
*The comparative mortality of an elite group in the long run of history: an observational analysis of politicians from 11 countries Full Text
*Height may be risk factor for multiple health conditions Full Text

Opinion/Editorials/Theory
An explanation for negligible senescence in animals Full Text

Other Ageing Biology
The benefits of exercise in a pill? Science is closer to that goal Abstract
Small-molecule activation of OGG1 increases oxidative DNA damage repair by gaining a new function
Human organ rejuvenation by VEGF-A: Lessons from the skin Full Text

Regenerative Medicine
*Surgeons transplant 3D ear made of living cells
Promoting exogenous repair in multiple sclerosis: myelin regeneration Full Text

Reproductive Health
*Clinical Efficacy of Curcumin and Vitamin E on Inflammatory-Oxidative Stress Biomarkers and Primary Symptoms of Menopause in Healthy Postmenopausal Women: A Triple-Blind Randomized Controlled Trial Full Text
Nicotinamide mononucleotide supplementation improves the quality of porcine oocytes under heat stress Full Text
*Associations between epigenetic age acceleration and infertility Full Text

Reviews
A Comprehensive Overview of the Complex Role of Oxidative Stress in Aging, The Contributing Environmental Stressors and Emerging Antioxidant Therapeutic Interventions Full Text
Multidimensional insights into the repeated electromagnetic field stimulation and biosystems interaction in aging and age-related diseases Full Text
The Effects of Dietary Advanced Glycation End-Products on Neurocognitive and Mental Disorders Full Text

Senolytics/Senescent Cells
Senotherapy Protects against Cisplatin-Induced Ovarian Injury by Removing Senescent Cells and Alleviating DNA Damage Full Text
Clearance of senescent cells with ABT-263 improves biological functions of synovial mesenchymal stem cells from osteoarthritis patients Full Text
Selective Elimination of Senescent Fibroblasts by Targeting the Cell Surface Protein ACKR3 Full Text

Skin & Beauty
Blood Donation Slows Skin Aging in Mice Abstract
*Cell-Free Blood Cell Secretome (BCS) Counteracts Skin Aging: Multi-Center Prospective Regenerative Aesthetic Medicine Study Using Exokine® Full Text
*Effectiveness of Dietary Supplement for Skin Moisturizing in Healthy Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials Full Text

Stem Cells
Human umbilical cord-derived mesenchymal stromal cells ameliorate aging-associated skeletal muscle atrophy and dysfunction by modulating apoptosis and mitochondrial damage in SAMP10 mice Full Text
Engrafted glial progenitor cells yield long-term integration and sensory improvement in aged mice Full Text
Human gingival mesenchymal stem cells retain their growth and immunomodulatory characteristics independent of donor age Full Text

Telomeres
*Telomere length and brain aging: A systematic review and meta-analysis Full Text
*Effect of a lifestyle intervention on telomere length:A systematic review and meta-analysis
*Genetic, parental and lifestyle factors influence telomere length Full text

Odds & Sods
Organ storage a step closer with cryopreservation discovery Abstract
Secrets of aging revealed in largest study on longevity, aging in reptiles and amphibians Abstract

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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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