February 2023 Longevity Review

Posted by Chris Pollyanna , 08 March 2023 · 1,190 views

supplements nad+ nmn curcumin astaxanthin fasting rapamycin metformin

February turned out to be a relatively fallow month for the longevity field, yet still served up a number of tasty morsels as we hid under the duvet awaiting the end of winter. There was finally a new senolytic result (though only a safety study) hope for presbyopia and some actionable results for oral hygiene and the best times of day to exercise.

In the supplemental section there was good news if you like blueberries and nuts, as well as reasons to increase your legume consumption, not to mention astaxanthin for improved IVF and curcumin for prostate health.

Canadian Longevity Association

Canadian Longevity Association YouTube Channel - where you can find video talk-throughs of these reviews.

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 if you want to buy me a coffee.
CLA News

Apart from getting some more free management and productivity tools such as Monday.com and Slack for nonprofit, the big news for us is that we flipped over our website to our Wordpress managed account, which means that we will finally be able to start expanding it, though equally it means we need more volunteers with website experience to help us do so! The biggest change is that the website is now bilingual for our Quebecois friends - tres bien!

A special mention should also be made for our friends down south at the Alliance for Longevity Initiatives who successfully launched the Longevity Science Caucus, a bipartisan grouping in congress to promote policies which support longevity research. They have already offered their help in achieving something similar in Canada.

February 2023 Round-Up:

Starting the roundup with hopefully the first of many senolytic trial results to be released this year. This small study in idiopathic pulmonary fibrosis, using dasatinib & quercetin, was primarily a safety study and in that at least it was successful as there were no serious adverse events, and perhaps a hint of efficacy, but way too small and short of duration to be read into. It will inform future trial designs.
*Senolytics dasatinib and quercetin in idiopathic pulmonary fibrosis: results of a phase I, single-blind, single-center, randomized, placebo-controlled pilot trial on feasibility and tolerability Full Text

As someone on the verge of presbyopia, this study caught my eye (pun fully intended!) as it showed the substance, aggrelyte-2, could decrease the stiffness in cultured human and mouse lenses. Animal studies are planned, so something to keep an eye on (there I go again... ).
Aggrelyte-2 promotes protein solubility and decreases lens stiffness through lysine acetylation and disulfide reduction: Implications for treating presbyopia Full Text

Calorie restriction (CR) was the first means found to increase lifespan in animals, but it has been difficult to prove that this translates to humans for obvious time dependent reasons, not to mention the difficulty in consistently eating less over the course of a life. Short term studies have taken place however, where biomarkers are used as surrogates, showing positive trends. In this latest analysis of one such study, it was found that there was a modest slowing in the pace of ageing which could translate to a 10-15% reduction in mortality. Good luck to you if you want to try this at home!
*Caloric Restriction Might Slow Down Human Aging Full Text

Moving on to two more easily achievable means of lowering your mortality risk, the first being oral hygiene with this study showing that those who regularly brush and floss had a 51% lower cardiovascular mortality over 18 years compared to those who did neither. However, mouthwash use did not further lower it.
*Oral hygiene, mouthwash usage and cardiovascular mortality during 18.8 years of follow-up Full Text

More difficult to achieve for those who have a job, engaging in moderate to vigorous physical activity (MVPA) between 11am and 5pm showed the greatest mortality risk reduction compared to both earlier or later in this study of 92,000 UK Biobank participants who wore accelerometers. However, MVPA at any time of day reduced mortality, with the benefit starting to plateau after 150 minutes a week.
*Midday Exercise Might Be Better In Preventing Mortality Full Text

And finally, this non-randomized study of men with lower urinary tract symptoms saw a reduction in prostate volume and PSA, as well an improvement in urinary flow after adding a curcumin formulation for one year to their standard of care.
*Efficacy of 1-Year Cavacurmin® Therapy in Reducing Prostate Growth in Men Suffering from Lower Urinary Tract Symptoms Full Text

Supplemental Section

Lifestyle
*Life’s Essential 8 and the risk of cardiovascular disease death and all-cause mortality in Finnish men Full Text
*Getting good sleep could add years to your life 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.
Dietary phosphate restriction prevents the appearance of sarcopenia signs in old mice Full Text
*Body shape perception in men and women without obesity during caloric restriction: a secondary analysis from the CALERIE study Full Text
*Comparison of the effects of six-week time-restricted eating on weight loss, body composition, and visceral fat in overweight older men and women Full Text
Fasting: From Physiology to Pathology Full Text

Diet – let food be thy medicine…
*Ultra-processed food consumption, cancer risk and cancer mortality: a large-scale prospective analysis within the UK Biobank Full Text
*Mediterranean diet in the management and prevention of obesity Full Text
*Impact of Nut Consumption on Cognition across the Lifespan Full Text
*Daily blueberry consumption for 12 weeks improves endothelial function in postmenopausal women with above-normal blood pressure through reductions in oxidative stress: a randomized controlled trial Full Text
*Dietary diversity and risk of late-life disabling dementia in middle-aged and older adults Full Text

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
Time of day may determine the amount of fat burned by exercise Full Text
*Senolytic effect of high intensity interval exercise on human skeletal muscle Full Text
*Long-term intensive endurance exercise training is associated to reduced markers of cellular senescence in the colon mucosa of older adults 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 treatment ameliorates ER stress in polycystic ovary syndrome patients: a randomized clinical trial Full Text
Astaxanthin Alleviates Foam Cell Formation and Promotes Cholesterol Efflux in Ox-LDL-Induced RAW264.7 Cells via CircTPP2/miR-3073b-5p/ABCA1 Pathway 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.
*Therapeutic Effect of Curcumin on Metabolic Diseases: Evidence from Clinical Studies Full Text
*Antioxidant and anti-inflammatory effects of curcumin/turmeric supplementation in adults: A GRADE-assessed systematic review and dose–response meta-analysis of randomized controlled trials

Fisetin
Fisetin Prevents Angiogenesis in Diabetic Retinopathy by Downregulating VEGF 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 and Health: Insights of Melatonin Action, Biological Functions, and Associated Disorders Full Text
Oxidative Stress and Aging as Risk Factors for Alzheimer’s Disease and Parkinson’s Disease: The Role of the Antioxidant Melatonin Full Text
Melatonin Supplement Plus Exercise Effectively Counteracts the Challenges of Isoproterenol-Induced Cardiac Injury in Rats Full Text

Nicotinamide MonoNucleotide (NMN)
*Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial Full Text
*Nicotinamide Adenine Dinucleotide Augmentation in Overweight or Obese Middle-Aged and Older Adults: A Physiologic Study

Nicotinamide Riboside (NR)
Boosting NAD ameliorates hematopoietic impairment linked to short telomeres in vivo Full Text

Resveratrol
*Effects of resveratrol supplementation on cardiac remodeling in hypertensive patients: a randomized controlled clinical trial
Exploring the mechanism of anti-fatigue of resveratrol based on network pharmacology and molecular docking, and in vitro studies Full Text
Protective role of resveratrol against VCM-induced hepatotoxicity in male wistar rats Full Text

Spermidine
Effects of Spermidine on Mouse Gut Morphology, Metabolites, and Microbial Diversity Full Text
Spermidine reduced neuropathic pain in chronic constriction injury-induced peripheral neuropathy in rats

Other available supplements (in alphabetical order)
*Role of β-Alanine Supplementation on Cognitive Function, Mood, and Physical Function in Older Adults; Double-Blind Randomized Controlled Study Full Text
The Preventive Effect of Specific Collagen Peptides against Dexamethasone-Induced Muscle Atrophy in Mice Full Text
*Vitamin D and Risk for Type 2 Diabetes in People With Prediabetes : A Systematic Review and Meta-analysis of Individual Participant Data From 3 Randomized Clinical Trials
*25-hydroxyvitamin D level is associated with greater grip strength across adult lifespan – a population-based cohort study Full Text
*Effects of molecular hydrogen supplementation on fatigue and aerobic capacity in healthy adults: A systematic review and meta-analysis Full Text
*Myo-inositol supplementation improves cardiometabolic factors, anthropometric measures, and liver function in obese patients with non-alcoholic fatty liver disease Full Text
*The Role of Omega-3 Polyunsaturated Fatty Acids and Their Lipid Mediators on Skeletal Muscle Regeneration: A Narrative Review Full Text

Combinations of Supplements
Melatonin/nicotinamide mononucleotide/ubiquinol: a cocktail providing superior cardioprotection against ischemia/reperfusion injury in a common co-morbidities modelled rat
The additive effects of nicotinamide mononucleotide and melatonin on mitochondrial biogenesis and fission/fusion, autophagy, and microRNA-499 in the aged rat heart with reperfusion injury
Spermidine-Eugenol Supplement Preserved Inflammation-Challenged Intestinal Cells by Stimulating Autophagy Full Text
*Comparison of the efficacy of pioglitazone and metformin on ultrasound grade and liver enzymes level in patients with non-alcoholic fatty liver disease: A randomized controlled clinical trial

Prescription Supplements

Metformin
Metformin use history and genome-wide DNA methylation profile: potential molecular mechanism for aging and longevity Full Text
*Association of metformin exposure with low risks of frailty and adverse outcomes in patients with diabetes Full Text
Pleiotropic Effects of Metformin in Osteoarthritis Full Text

Rapamycin (sirolimus)
Intra-articular injection of rapamycin microparticles prevent senescence and effectively treat osteoarthritis Full Text
Osteogenic effects of rapamycin on bone marrow mesenchymal stem cells via inducing autophagy Full Text

Miscellaneous Molecules & Prescription Drugs
Long-term administration of CU06-1004 ameliorates cerebrovascular aging and BBB injury in aging mouse model Full Text
*Newer glucose-lowering drugs and risk of dementia: A systematic review and meta-analysis of observational studies
Mitochondrial-Encoded Peptide MOTS-c, Diabetes, and Aging-Related Diseases Full Text
Mapping the metabolic reprogramming induced by sodium-glucose cotransporter 2 inhibition Full Text

Other Areas of Interest (in alphabetical order)

Ageing Clocks & other biomarkers of ageing
*Nonlinear Analysis for a Better Epigenetic Clock Full Text
*DNAmFitAge: biological age indicator incorporating physical fitness Full Text
*Epigenetic-based age acceleration in a representative sample of older Americans: Associations with aging-related morbidity and mortality Full Text

Exosomes (small packets of information released by cells)
Extracellular Vesicles in Aging: An Emerging Hallmark? Full Text
Mesenchymal and Neural Stem Cell-Derived Exosomes in Treating Alzheimer’s Disease Full Text
Extracellular Vesicles as “Very Important Particles” (VIPs) in Aging Full Text

Genetics including CRISPR
The State of the Art in Immune Cell Therapy Abstract
*Testing their strength: CAR T-cells combat muscle inflammation Full Text
A meta-analysis of RNA-Seq studies to identify novel genes that regulate aging Full Text

Lifespan Lengthening Interventions
The effect of a pharmaceutical ghrelin agonist on lifespan in C57BL/6J male mice: A controlled experiment Full Text
Loss of smelling is an early marker of aging and is associated with inflammation and DNA damage in C57BL/6J mice Full Text NR
Naringin Alleviates Glucose-Induced Aging by Reducing Fat Accumulation and Promoting Autophagy in Caenorhabditis elegans Full Text

Microbiome
Gut microbiota remodeling improves natural aging-related disorders through Akkermansia muciniphila and its derived acetic acid Full Text
Lactobacillus gasseri NK109 and Its Supplement Alleviate Cognitive Impairment in Mice by Modulating NF-κB Activation, BDNF Expression, and Gut Microbiota Composition Full Text
Prebiotic mechanisms of resistant starches from dietary beans and pulses on gut microbiome and metabolic health in a humanized murine model of aging Full Text
Akkermansia muciniphila as a Next-Generation Probiotic in Modulating Human Metabolic Homeostasis and Disease Progression: A Role Mediated by Gut–Liver–Brain Axes? Full Text
Effects of Berries, Phytochemicals, and Probiotics on Atherosclerosis through Gut Microbiota Modification: A Meta-Analysis of Animal Studies Full Text

Observational Studies
*Poorer sleep impairs brain health at midlife Full Text
*Mothers of small-bodied children and fathers of vigorous sons live longer Full Text
Association Between BMI and Mortality Revisited Abstract
*Predictors of healthy physiological aging across generations in a 30-year population-based cohort study: the Doetinchem Cohort Study Full Text
*Blood levels of nicotinic acid negatively correlate with hearing ability in healthy older men Full Text

Opinion/Editorials/Theory
Longevity Science and Women’s Health and Wellbeing Full Text (Jan 2023)
Mitochondrial ROS production, oxidative stress and aging within and between species: Evidences and recent advances on this aging effector Full Text
Limits to lifespan growth Full Text (Jan 2023)
Antagonistic pleiotropy: the example of cardiac insulin-like growth factor signaling, which is essential in youth but detrimental in age Full Text

Other Ageing Biology
AlphaFold accelerates artificial intelligence powered drug discovery: efficient discovery of a novel CDK20 small molecule inhibitor Full Text (Jan 2023)
The multi-tissue landscape of somatic mtdna mutations indicates tissue specific accumulation and removal in aging Full Text
A Relationship Between NAD+ and Gradual Heart Failure Full Text

Regenerative Medicine
Biomineralization-inspired mineralized hydrogel promotes the repair and regeneration of dentin/bone hard tissue Full Text
Human Organoids for Brain Regeneration Abstract

Reproductive Health
Reprogramming of ovarian aging epigenome by resveratrol Full Text
*The effect of Curcumin on metabolic parameters and androgen level in women with polycystic ovary syndrome: a randomized controlled trial Full Text
Improvement of oocyte quality through the SIRT signaling pathway Full Text
*Age-related methylation changes in the human sperm epigenome Full Text

Reviews
Hallmarks of neurodegenerative diseases Full Text
*Association of inflammation and cognition in the elderly: A systematic review and meta-analysis Full Text
The Central Role of the NAD+ Molecule in the Development of Aging and the Prevention of Chronic Age-Related Diseases: Strategies for NAD+ Modulation Full Text

Senolytics/Senescent Cells
A Light-Sensitive Drug to Remove Senescent Cells Abstract
A novel role of Fas in delaying cellular senescence Full Text
Local senolysis in aged mice only partially replicates the benefits of systemic senolysis Full Text

Skin & Beauty
*The synergistic effect of retinyl propionate and hydroxypinacolone retinoate on skin aging Full Text
*Significant Reversal of Facial Wrinkle, Pigmented Spot and Roughness by Daily Application of Galactomyces Ferment Filtrate-Containing Skin Products for 12 Months—An 11-Year Longitudinal Skin Aging Rejuvenation Study Full Text
*Benefits of the Dermocosmetic Mineral 89 Probiotic Fractions Adjunct to Topical Retinoids for Anti-Aging Benefits Full Text
*Efficacy and Safety of the Genistein Nutraceutical Product Containing Vitamin E, Vitamin B3, and Ceramide on Skin Health in Postmenopausal Women: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial Full Text

Stem Cells
*Novel heart failure treatment using cell therapy Full Text
Transcriptional reprogramming of skeletal muscle stem cells by the niche environment Full Text
Transfer of Cardiac Mitochondria Improves the Therapeutic Efficacy of Mesenchymal Stem Cells in a Preclinical Model of Ischemic Heart Disease Full Text

Telomeres
Influence of telomerase activity and initial distribution on human follicular aging: Moving from a discrete to a continuum model Full Text
A Multivitamin Mixture Protects against Oxidative Stress-Mediated Telomere Shortening Full Text

**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.*
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------