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December 2023 Longevity Review
longevity supplements exercise fasting fisetin nmn resveratrol
As we wrapped up the year and took a well deserved holiday break, the longevity studies kept on coming. This month we will take a look at the latest results from the ITP, the gold standard of longevity studies; how CD38 is a prime culprit for ovarian ageing and lung fibrosis, and how it can be counteracted; how high consumption of fruits and vegetables increases mouse average lifespan; and, how a new substance, originally from carrots, increases the healthspan of elderly mice.
In addition, in the supplemental section, you’ll find reviews collagen for skin, magnesium for muscles and NAC for the arteries; how drinking tea reduces biological age; how fisetin improves arterial function; how organs age at different rates; and even how the lifespan of bumblebees can be extended! Plus of course much more.
Canadian Longevity Association News
December saw two new volunteers, Elizabeth and Tayseer, join our growing team - so a warm welcome to them both! We also received our first major (for us) donation, which will allow us to expand our activities in 2024. In addition, we had our first Christmas longevity dinner, which turned out to be a great success with 17 people attending. If you’re in Toronto, make sure to join next year’s one!
Donate to the Canadian Longevity Association
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Previous newsletters can be found in the CLA Facebook Group, and also my Patreon account, which includes bonus material for supporters if you want to buy us a coffee.
Finally, 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.
December 2023 Round-Up:
It's always a good day when the Interventions Testing Program releases a new set of results, especially when a couple of the molecules are shown to extend median lifespan - and extra especially if one of those molecules is a supplement I take!
In this latest release, astaxanthin (which I take) increased median lifespan in males by 12%, while meclizine increased it by 8%. Unfortunately, the results were sex specific. Also unfortunately, fisetin, SG1002 (hydrogen sulfide donor), dimethyl fumarate, mycophenolic acid, and 4-phenylbutyrate did not show a statistically significant change at the doses tested.
Astaxanthin and Meclizine Extend Lifespan in Mice
Astaxanthin and meclizine extend lifespan in UM-HET3 male mice; fisetin, SG1002 (hydrogen sulfide donor), dimethyl fumarate, mycophenolic acid, and 4-phenylbutyrate do not significantly affect lifespan in either sex at the doses and schedules used Full Text
We all know that fruit & vegetables (F&V) are good for us, but here is the first study to show what elevated consumption of F&V does over the course of an entire life. Mice were fed high or low fat diets, with or without high levels of F&V, and those with high F&V had a higher median lifespan, lower tumor incidence and improvements in various other biomarkers.
Life-long consumption of high level of fruits and vegetables reduces tumor incidence and extends median lifespan in mice Full Text
Originally found in carrots, isofalcarintriol extended the lifespan of worms, and improved glucose metabolism and exercise endurance while decreasing frailty in mice. Although it didn’t extend lifespan in mice, it’s beneficial effects were observed at very low doses which could indicate that its bioavailability is much better than similar natural substances such as resveratrol.
A naturally occurring polyacetylene isolated from carrots promotes health and delays signatures of aging Full Text
Ovaries are the first major organ to succumb to ageing, leading to much earlier female age-related infertility. The main culprit, according to the first paper, is elevated levels of CD38, which deplete NAD+ and which can be reversed by a CD38 inhibitor, c78, leading to improved egg quality and increased litter size in aged mice. The second paper unveils a new CD38 inhibitor, Ab68, which prevents fibrosis in mice and might be superior for potential side effects as it does not cross the blood-brain barrier.
Heavy-chain antibody targeting of CD38 NAD+ hydrolase ectoenzyme to prevent fibrosis in multiple organs Full Text
NADase CD38 is a key determinant of ovarian aging 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.
*Earlier Meals Associated with Less Vascular Disease Full Text
Exercise and Caloric Restriction Exert Different Benefits on Skeletal Muscle Metabolism in Aging Condition Full Text
A long-term ketogenic diet in young and aged rats has dissociable effects on prelimbic cortex and CA3 ensemble activity Full Text
Diet – let food be thy medicine…
*Adherence to the EAT-Lancet reference diet is associated with a reduced risk of incident cancer and all-cause mortality in UK adults Full Text
*The Southern European Atlantic diet and all-cause and cause-specific mortality: a European multicohort study Full Text
*Tea consumption and attenuation of biological aging: a longitudinal analysis from two cohort studies Full Text (Nov 2023)
Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*Different resistance training volumes on strength, functional fitness, and body composition of older people: A systematic review with meta-analysis
*The association between chrononutrition behaviors and muscle health among older adults: The study of muscle, mobility and aging Full Text
*An acute bout of high-intensity exercise affects nocturnal sleep and sleep-dependent memory consolidation 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 Protects against Alcoholic Liver Injury via Regulating Mitochondrial Redox Balance and Calcium Homeostasis
Dietary Astaxanthin: A Promising Antioxidant and Anti-Inflammatory Agent for Brain Aging and Adult Neurogenesis 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.
*The effects of curcumin-piperine supplementation on inflammatory, oxidative stress and metabolic indices in patients with ischemic stroke in the rehabilitation phase: a randomized controlled trial Full Text
Targeted therapies of curcumin focus on its therapeutic benefits in cancers and human health: Molecular signaling pathway-based approaches and future perspectives Full Text
Anti-inflammatory effect of curcumin in an accelerated senescence model of Wistar rat: an in vivo and in-silico study
Fisetin
Exploring the anti-aging effects of fisetin in telomerase-deficient progeria mouse model Full Text
Fisetin, a dietary flavonoid, promotes transintestinal cholesterol excretion through the activation of PPARδ
Fisetin Inhibits UVA-Induced Expression of MMP-1 and MMP-3 through the NOX/ROS/MAPK Pathway in Human Dermal Fibroblasts and Human Epidermal Keratinocytes Full Text
Melatonin
*Melatonin supplementation does not alter vascular function or oxidative stress in healthy normotensive adults on a high sodium diet Full Text
Melatonin facts: Lack of evidence that melatonin is a radical scavenger in living systems Full Text
Melatonin as a chronobiotic/cytoprotective agent in bone. Doses involved Full Text
Nicotinamide MonoNucleotide (NMN)
Nicotinamide mononucleotide as a therapeutic agent to alleviate multi-organ failure in sepsis Full Text
Nicotinamide mononucleotide alleviates endotoxin-induced acute lung injury by modulating macrophage polarization via the SIRT1/NF-κB pathway Full Text
The identification of new roles for nicotinamide mononucleotide after spinal cord injury in mice: an RNA-seq and global gene expression study Full Text
Nicotinamide Riboside (NR)
Chronic dietary supplementation with nicotinamide riboside reduces sleep need in the laboratory mouse Full Text
Pterostilbene
Pterostilbene alleviates abdominal aortic aneurysm via inhibiting macrophage pyroptosis by activating the miR-146a-5p/TRAF6 axis
Stilbenes: a promising small molecule modulator for epigenetic regulation in human diseases Full Text
Resveratrol
Cardiovascular risk of dietary trimethylamine oxide precursors and the therapeutic potential of resveratrol and its derivatives Full Text
Resveratrol and Gut Microbiota Synergy: Preventive and Therapeutic Effects Full Text
Prophylactic oral application of resveratrol to alleviate acute campylobacteriosis in human gut microbiota associated IL-10−/− mice Full Text
Spermidine
Metabolism of Polyamines and Kidney Disease: A Promising Therapeutic Target Full Text
Other available supplements or natural substances (in alphabetical order)
*Daily low-dose aspirin and incident type 2 diabetes in community-dwelling healthy older adults: a post-hoc analysis of efficacy and safety in the ASPREE randomised placebo-controlled trial
Therapeutic Applications of Ginseng Natural Compounds for Health Management Full Text
*Supplementation with β-hydroxy-β-methylbutyrate after resistance training in post-acute care patients with sarcopenia: A randomized, double-blind placebo-controlled trial
The Integral Role of Magnesium in Muscle Integrity and Aging: A Comprehensive Review Full Text
N-Acetylcysteine and Atherosclerosis: Promises and Challenges Full Text
*Omega-3 Blood Levels and Stroke Risk: A Pooled and Harmonized Analysis of 183 291 Participants From 29 Prospective Studies Full Text
Traditional herbs: mechanisms to combat cellular senescence Full Text
Preventative and therapeutic potential of tocotrienols on musculoskeletal diseases in ageing Full Text
Combinations of Supplements/Treatments
Geroprotector drugs and exercise: friends or foes on healthy longevity? Full Text
Reprogramming Macrophage Polarization, Depleting ROS by Astaxanthin and Thioketal-Containing Polymers Delivering Rapamycin for Osteoarthritis Treatment Full Text
*Combined Rehabilitation with Alpha Lipoic Acid, Acetyl-L-Carnitine, Resveratrol, and Cholecalciferolin Discogenic Sciatica in Young People: A Randomized Clinical Trial Full Text
Prescription Supplements
Metformin
*The effect of metformin on adipokines levels: A systematic review and meta-analysis of randomized-controlled trials
*Metformin reduces decline in the estimated glomerular filtration rate during progression of autosomal dominant polycystic kidney disease: a systematic review and meta-analysis Full Text
Miscellaneous Molecules & Prescription Drugs
BIO101 stimulates myoblast differentiation and improves muscle function in adult and old mice Full Text
Cabozantinib prevents AGEs-induced degradation of type 2 collagen and aggrecan in human chondrocytes Full Text
*Statins, Mortality, and Major Adverse Cardiovascular Events Among US Veterans With Chronic Kidney Disease Full Text
*Statins and cognitive decline in patients with Alzheimer’s and mixed dementia: a longitudinal registry-based cohort study Full Text
Other Areas of Interest (in alphabetical order)
Ageing Clocks & other biomarkers of ageing
*Organ aging signatures in the plasma proteome track health and disease Full Text
*Associations between biological ageing and the risk of, genetic susceptibility to, and life expectancy associated with rheumatoid arthritis: a secondary analysis of two observational studies Full Text
*Predicting 1-, 3-, 5-, and 8-year all-cause mortality in a community-dwelling older adult cohort: relevance for predictive, preventive, and personalized medicine Full Text
Blood Factors or other Heterochronic Transplantation
Supernatant of activated platelet-rich plasma rejuvenated aging-induced hyposalivation in mouse Full Text
Rejuvenation of cerebromicrovascular function in aged mice through heterochronic parabiosis: insights into neurovascular coupling and the impact of young blood factors
Epigenetics & Cellular Reprogramming
Partial cellular reprogramming: A deep dive into an emerging rejuvenation technology Full Text
DNA methylation rates scale with maximum lifespan across mammals Full Text
Sustained Vision Recovery by OSK Gene Therapy in a Mouse Model of Glaucoma
Exosomes (small packets of information released by cells)
Effect of miR-21 in mesenchymal stem cells-derived extracellular vesicles behavior Full Text
Extracellular vesicles (EVs): A promising therapeutic tool in the heart tissue regeneration Full Text
Genetics including CRISPR
*Evidence for the role of selection for reproductively advantageous alleles in human aging Full Text
*Genetic associations with longevity are on average stronger in females than in males Full Text
*Genetic insights into the association of statin and newer nonstatin drug target genes with human longevity: a Mendelian randomization analysis Full Text
Lifespan Lengthening Interventions
DNA methylation extends lifespan in the bumblebee Bombus terrestris Full Text
Anti-aging Effect of Rutin in Caenorhabditis elegans and D-Gal-Induced Aging Mouse Model
SKN-1/NRF2 upregulation by vitamin A is conserved from nematodes to mammals and is critical for lifespan extension in Caenorhabditis elegans Full Text
Microbiome
Probiotics Attenuate Myopathic Changes in Aging Rats via Activation of the Myogenic Stellate Cells Full Text
*Disentangling the age-related manner in the associations between gut microbiome and women’s health: a multi-cohort microbiome study Full Text
Targeting gut microbiota in aging-related cardiovascular dysfunction: focus on the mechanisms Full Text
Observational Studies
*Low-density-lipoprotein cholesterol and mortality outcomes among healthy older adults: A post-hoc analysis of ASPREE trial Full Text
*The Phenotypic Characterization of the Oldest Italian Man from December 28, 2020, to September 23, 2021, A.T., Strengthens the Idea That the Immune System can Play a Key Role in the Attainment of Extreme Longevity Full Text
*Does urban greenness reduce loneliness and social isolation among Canadians? A cross-sectional study of middle-aged and older adults of the Canadian Longitudinal Study on Aging (CLSA) Full Text
Opinion/Editorials/Theory
Leveraging AI to identify dual-purpose aging and disease targets Full Text
Enabling translational geroscience by broadening the scope of geriatric care Full Text
Three common assumptions about inflammation, aging, and health that are probably wrong
Healthy aging: Linking causal mechanisms with holistic outcomes Full Text
Other Ageing Biology
Recapitulation of anti-aging phenotypes by global overexpression of PTEN in mice Full Text
Systematic assessment of transcriptomic and metabolic reprogramming by blue light exposure coupled with aging Full Text
Reproductive Health
Impact of NAD+ metabolism on ovarian aging Full Text
Delivering umbilical cord mesenchymal stem cell exosomes through hydrogel ameliorates vaginal atrophy in ovariectomized rats Full Text
Reviews
Aging Hallmarks and Progression and Age-Related Diseases: A Landscape View of Research Advancement Full Text
The regulatory effect of growth differentiation factor 11 on different cells Full Text
Umbrella review and Delphi study on modifiable factors for dementia risk reduction Full Text
PCSK9: an emerging player in cardiometabolic aging and its potential as a therapeutic target and biomarker Full Text
Metabolic pathways in immune senescence and inflammaging: Novel therapeutic strategy for chronic inflammatory lung diseases. An EAACI position paper from the Task Force for Immunopharmacology Full Text
Age-Related Alternative Splicing: Driver or Passenger in the Aging Process? Full Text
Senolytics/Senescent Cells
Senotherapeutic drug treatment ameliorates chemotherapy-induced cachexia Full Text
Intermittent supplementation with fisetin improves arterial function in old mice by decreasing cellular senescence Full Text
Non-Intrinsic, Systemic Mechanisms of Cellular Senescence Full Text
Skin & Beauty
Umbilical cord-derived mesenchymal stem cell secretome promotes skin regeneration and rejuvenation: From mechanism to therapeutics Full Text
*Exploring the Impact of Hydrolyzed Collagen Oral Supplementation on Skin Rejuvenation: A Systematic Review and Meta-Analysis Full Text
*Immunomodulation with AM3 and antioxidants creates an adequate framework for skin repair and decreases the monocyte proinflammatory stage in smoker women Full Text
Stem Cells
Endothelial progenitor cells systemic administration alleviates multi-organ senescence by down-regulating USP7/p300 pathway in chronic obstructive pulmonary disease Full Text
Rewiring of IGF1 secretion and enhanced IGF1R signaling induced by co-chaperone carboxyl-terminus of Hsp70 interacting protein in adipose-derived stem cells provide augmented cardioprotection in aging-hypertensive rats Full Text
Mesenchymal stem cells lose the senescent phenotype under 3D cultivation Full Text
Telomeres
*Unraveling the causal genes and transcriptomic determinants of human telomere length Full Text
Diet and Aging: The Role of Polyphenol-Rich Diets in Slow Down the Shortening of Telomeres: A Review Full Text
Odds & Sods
Exergames improve cognitive function in older adults and their possible mechanisms: A systematic review Full Text
Songbirds avoid the oxidative stress costs of high blood glucose levels: a comparative study Full Text
Optimum ratio of dietary protein and carbohydrate that maximises lifespan is shared among related insect species 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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