June 2023 Longevity Review

As we round off the first half of the year, the big story from June was that taurine was shown to potentially boost both lifespan in mice and healthspan in monkeys. In addition, there was more progress in translating senolytics to humans with a long term monkey study, as well as using AI to discover additional senolytic molecules. To get an idea why senolytics could be so important, head on over to the review section, where there are a couple of reviews on the harmful effects of inflammation, which senolytics counter. Sticking with reviews, there is also a thorough review of ovarian ageing and potential treatments in the reproductive health section. And of course, plenty more!

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And, as you can see at the top of the page, we have had our logo updated to include a maple leaf. This came about through the initiative of our volunteer Myles, who was able to get a professional designer, Dwight Alexander, to help us out - so a big thank you to both Dwight and Myles!

June 2023 Round-Up:

This study caused quite a stir when it was released, even making it onto the front page of the BBC. It showed that the amino acid, taurine, could extend mouse lifespan by 10-12% as well improve the health of older monkeys. The impressive aspect was that the study went all the way from yeast, through worms and mice, to monkeys. Maybe hold off buying case loads of Red Bull, but this should be readily testable in humans, and hopefully we will hear more about this soon.
Taurine Increases Median Lifespan in Mice by 12% Full Text

While we eagerly await the results of human senolytic trials, here is a six month study in middle-aged monkeys which showed that the combination of dasatinib and quercetin (D & Q) was safe and had promising results for inflammaging, intestinal barrier and renal function, as well as improved metabolic health. Monkeys are a lot closer to humans than mice, so this is a good indication.
Benefits of Dasatinib and Quercetin Treatment in Monkey Abstract

Sticking with the senolytics D & Q, here are a couple more studies, the first one showing their potential benefit, by boosting neurogenesis in a short lived fish, while the second one demonstrates that they (along with fisetin) can have sex specific effects in mice when administered from an early age.
A short dasatinib and quercetin treatment is sufficient to reinstate potent adult neuroregenesis in the aged killifish Full Text
Sexual dimorphic metabolic and cognitive responses of C57BL/6 mice to Fisetin or Dasatinib and quercetin cocktail oral treatment Full Text

With all the recent hoopla about AI taking over our jobs and the world, this paper shows how it can be harnessed to speed up and reduce the cost of developing new drugs. In this instance, machine learning was used to discover some new senolytics - for while D & Q are effective, they are not perfect and we are going to need different senolytics for different cell types.
Discovery of senolytics using machine learning Full Text

And finally, moving away from senolytics, this study shows how exosomes derived from induced pluripotent stem cells could improve blood vessel growth in the heart and total antioxidant capacity of aged mice.
iPSC-derived exosomes promote angiogenesis in naturally aged mice 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.
Post-Effects of Time-Restricted Feeding against Adipose Tissue Inflammation and Insulin Resistance in Obese Mice Full Text
Is caloric restriction enough to increase longevity? Fasting and circadian alignment Full Text
The effects of graded levels of calorie restriction: XX. impact of long term graded calorie restriction on survival and body mass dynamics in male C57BL/6J mice Full Text

Diet – let food be thy medicine…
*Higher versus lower nut consumption and changes in cognitive performance over two years in a population at risk of cognitive decline: a cohort study Full Text
*Potential neuroprotective effects of fermented foods and beverages in old age: a systematic review Full Text
Neuroprotective Effects of Black Pepper and Its Bioactive Compounds in Age-Related Neurological Disorders Full Text

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*Resistance training rejuvenates aging skin by reducing circulating inflammatory factors and enhancing dermal extracellular matrices Full Text
*Association of daily step volume and intensity with cardiometabolic risk in older adults Full Text
*Can exercise help counteract genetic risk of 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.

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 prevents osteoarthritis by blocking Rspo2-mediated Wnt/β-catenin signaling in chondrocytes and abolishing Rspo2-related inflammatory factors in macrophages Full Text
The Effect of Astaxanthin on Mitochondrial Dynamics in Rat Heart Mitochondria under ISO-Induced Injury 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.
Pharmacological Mechanisms and Clinical Applications of Curcumin: Update Full Text
The therapeutic potential of curcumin and its related substances in turmeric: From raw material selection to application strategies 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.
Melatonin: Facts, Extrapolations and Clinical Trials Full Text
*Effects of melatonin against acute kidney injury: A systematic review and meta-analysis

Nicotinamide MonoNucleotide (NMN)
NAD+ Precursors Nicotinamide Mononucleotide (NMN) and Nicotinamide Riboside (NR): Potential Dietary Contribution to Health Full Text

Nicotinamide Riboside (NR)
Improving Mitochondrial Function in Skeletal Muscle Contributes to the Amelioration of Insulin Resistance by Nicotinamide Riboside Full Text
Deletion of enzymes for de novo NAD+ biosynthesis accelerated ovarian aging Full Text

Resveratrol
Resveratrol, a SIRT1 activator, attenuates aging-associated alterations in skeletal muscle and heart in mice Full Text

Spermidine
*The positive effect of spermidine in older adults suffering from dementia after 1 year Full Text
Polyamines and Physical Activity in Musculoskeletal Diseases: A Potential Therapeutic Challenge Full Text
Spermidine from arginine metabolism activates Nrf2 and inhibits kidney fibrosis Full Text

Other available supplements (in alphabetical order)
Acarbose suppresses symptoms of mitochondrial disease in a mouse model of Leigh syndrome
Creatine on the Brain: A Review Full Text
*Vitamin D status & associations with inflammation in older adults Full Text
*About the associations of vitamin D deficiency and biomarkers of systemic inflammatory response with all-cause and cause-specific mortality in a general population sample of almost 400,000 UK Biobank participants Full Text
*Taking higher-than-recommended doses of vitamin D for five years reduced the risk of atrial fibrillation Full Text
Vitamin K and Hallmarks of Ageing: Focus on Diet and Gut Microbiome Full Text
*Does omega-3 supplementation improve the inflammatory profile of patients with heart failure? a systematic review and meta-analysis Full Text
*Protection of Liver Functions and Improvement of Kidney Functions by Twelve Weeks Consumption of Cuban Policosanol (Raydel®) with a Decrease of Glycated Hemoglobin and Blood Pressure Full Text
Pyrroloquinoline quinone alleviates natural aging-related osteoporosis via a novel MCM3-Keap1-Nrf2 axis-mediated stress response and Fbn1 upregulation Full Text

Combinations of Supplements
*A combined DHA-rich fish oil and cocoa flavanols intervention does not improve cognition or brain structure in older adults with memory complaints: results from the CANN randomized, controlled parallel-design study Full Text
*The acute effect of different NAD+ precursors included in the combined metabolic activators
*Preliminary evidence of the effects of a novel antioxidant supplement in reducing oxidative stress in patients with senile cataract Full Text
*Multivitamin/Multimineral Supplementation Prevents or Reverses Decline in Vitamin Biomarkers and Cellular Energy Metabolism in Healthy Older Men: A Randomized, Double-Blind, Placebo-Controlled Study Full Text

Prescription Supplements

Metformin
Metformin: A Review of Potential Mechanism and Therapeutic Utility Beyond Diabetes Full Text

Rapamycin (sirolimus)
Pre-treatment of rapamycin transformed M2 microglia alleviates traumatic cervical spinal cord injury via AIM2 signaling pathway in vitro and in vivo

Miscellaneous Molecules & Prescription Drugs
Metabolic benefits of 17α-estradiol in liver are partially mediated by ERβ in male mice Full Text
ISRIB alleviates aging-associated brown fat UCP1 translational repression and thermogenic deficiency
*Evidence of an anti-inflammatory effect of PCSK9 inhibitors within the human atherosclerotic plaque

Other Areas of Interest (in alphabetical order)

Ageing Clocks & other biomarkers of ageing
*Epigenetic and Metabolomic Biomarkers for Biological Age: A Comparative Analysis of Mortality and Frailty Risk Full Text
*Higher testosterone and testosterone/estradiol ratio in men are associated with decreased Pheno-/GrimAge and DNA-methylation based PAI1 Full Text
*Inequalities in urban greenness and epigenetic aging: Different associations by race and neighborhood socioeconomic status Full Text

Epigenetics & Cellular Reprogramming
Chemical-induced epigenome resetting for regeneration program activation in human cells Full Text (May 2023)
A Potential New Foundation for Epigenetic Clocks Full Text
Pluripotency-independent induction of human trophoblast stem cells from fibroblasts Full Text

Exosomes (small packets of information released by cells)
Therapeutic Applications of Plant-Derived Extracellular Vesicles as Antioxidants for Oxidative Stress-Related Diseases Full Text

Genetics including CRISPR
Identification of novel genes associated with exercise and calorie restriction effects in skeletal muscle Full Text
Gene expressions associated with longer lifespan and aging exhibit similarity in mammals Full Text

Lifespan Lengthening Interventions
Curcumin supplementation increases longevity and antioxidant capacity in Caenorhabditis elegans Full Text
Nicotinamide riboside functions during development while beta-hydroxybutyrate functions during adulthood to extend C. elegans lifespan Full Text
Effects of the dipeptides comprising leucine and lysine on lifespan and age-related stress in Caenorhabditis elegans Full Text

Microbiome
Resistant starches from dietary pulses modulate the gut metabolome in association with microbiome in a humanized murine model of ageing Full Text
Calorie restriction mimetic drugs could favorably influence gut microbiota leading to lifespan extension Full Text
Gut microbiome-mediated mechanisms in aging-related diseases: are probiotics ready for prime time? Full Text

Observational Studies
*Is there an association between daytime napping, cognitive function, and brain volume? A Mendelian randomization study in the UK Biobank Full Text
*Cross-sectional analysis of healthy individuals across decades: Aging signatures across multiple physiological compartments Full Text
*Subclinical atherosclerosis and accelerated epigenetic age mediated by inflammation: a multi-omics study Full Text

Opinion/Editorials/Theory
Synergistic Strategies to Accelerate the Development of Function-Promoting Therapies: Lessons From Operation Warp Speed and Oncology Drug Development Full Text
The cost of aging: Economic growth perspectives for Europe Full Text
Translational longevity medicine: a Swiss perspective in an ageing country Full Text

Other Ageing Biology
Increased Iron Levels and Oxidative Stress Mediate Age-Related Impairments in Male and Female Drosophila melanogaster Full Text
Sirtuin 2 deficiency aggravates ageing-induced vascular remodelling in humans and mice Full Text

Reproductive Health
*Metabolic Mechanisms and Potential Therapeutic Targets for Prevention of Ovarian Aging: Data from Up-to-Date Experimental Studies Full Text
*No Increase in Major Cardiac Events With Testosterone-Replacement Therapy Abstract
Growth hormone reduces aneuploidy and improves oocytes quality by JAK2-MAPK3/1 pathway in aged mice Full Text

Reviews
A Role for Advanced Glycation End Products in Molecular Ageing Full Text
Chronic Inflammation and the Hallmarks of Aging Full Text
Inflammation and aging: signaling pathways and intervention therapies Full Text
Extracellular Matrix Dynamics as an Emerging yet Understudied Hallmark of Aging and Longevity Full Text
Metabolo-epigenetic interplay provides targeted nutritional interventions in chronic diseases and ageing Full Text

Senolytics/Senescent Cells
Senolytic treatment with dasatinib and quercetin does not improve overall influenza responses in aged mice Full Text

Skin & Beauty
*Efficacy and safety of oral palmitoleic acid supplementation for skin barrier improvement: A 12-week, randomized, double-blinded, placebo-controlled study Full Text (May 2023)
The IL-17 protein plays a key role in skin ageing Full Text
*Efficacy of combined treatment with human adipose tissue stem cell-derived exosome-containing solution and microneedling for facial skin aging: A 12-week prospective, randomized, split-face study Full Text
*Skin Cellular Reprogramming as an Innovative Anti-Aging Strategy for Cosmetic Application: A Clinical Study of Sericoside Full Text

Stem Cells
hucMSCs treatment prevents pulmonary fibrosis by reducing circANKRD42-YAP1-mediated mechanical stiffness Full Text
Releasing YAP dysfunction-caused replicative toxicity rejuvenates mesenchymal stem cells Full Text

Telomeres
*Association between the anthropometric measurements and dietary habits on telomere shortening in healthy older adults: A-cross-sectional study Full Text
*Leukocyte telomere length and mitochondrial DNA copy number associate with endothelial function in aging-related cardiovascular disease Full Text
*Impact of Heartfulness meditation practice on anxiety, perceived stress, well-being, and telomere length Full Text

Odds & Sods
Transcranial Electromagnetic Wave Treatment: A Fountain of Healthy Longevity? Full Text
Preserved Kidneys Rewarmed and Transplanted in Rats Full Text
*Study shows promising treatment for tinnitus Full Text
Cellular Senescence Drives Regeneration in Cnidarians Full Text
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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 *starred any human trials.*
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