March 2024 Longevity Review

Posted by Chris Pollyanna , 14 April 2024 · 725 views

supplements young blood ergothioneine nad nmn rapamycin astaxanthin senolytics

As winter enters the rearview mirror, March’s highlights included three lifespan extending studies involving young blood plasma, a two drug synergistic combo and the main bioactive molecule found in mushrooms, and the Canadian content section returns with a groundbreaking study leveraging the powers of AI for drug development.

In addition to the above you will also find under NMN, a study showing it improves the lifespan of age accelerated mice; in Other Supplements, reviews of Apigenin and Kaempferol; in Epigenetics, an examination of chemical partial reprogramming; in Reproductive Health, two studies using stem cells to preserve ovarian function; in Skin & Beauty, two studies on the benefits of of taking collagen; and, at the very end in Odds & Sods, you can find a write up of the recent longevity network state of Vitalia and how, with the Million Molecule Challenge, you can help discover new longevity molecules. Plus of course much more!

Canadian Longevity Association News

We onboarded a new volunteer who has some skills with AI and is using them to help automate some of our processes, which will give us more time to work on more important stuff. Welcome aboard Barzin!

Our team is slowly but surely growing, and with each additional member and skillset, we will be able to accomplish more. Please consider joining our team to help us make even further progress.

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March 2024 Round-Up:

This is the first published study showing that young blood plasma can potentially extend the lifespan of a rat. I say potentially as this was a very small study, and one of the controls had the longest lifespan overall. However, the methylation age of the treated rats was also reduced, they supposedly showed more activity and their fur had an improved appearance. This is one field of longevity which has the potential to be transformative, but of course it is still early days and a lot more studies are needed before we can conclusively determine whether or not young plasma is rejuvenatory.
Young Plasma Rejuvenates Blood Dna Methylation Profile, Extends Mean Lifespan And Improves Physical Appearance In Old Rats Full Text

In this study, a couple of the popular NAD+ precursors were combined with another drug to synergistically extend the lifespan, and improve the physical performance, of fruit flies. Median lifespan extension went from 17% individually to 30% in combination. For us to make any headway in finding effective longevity interventions, we need to discover more of these synergistic combinations.
Dual treatment with kynurenine pathway inhibitors and NAD+ precursors synergistically extends life span in Drosophila Full Text

Great news if you love mushrooms as much as I do - ergothioneine, found mainly in fungi, is shown in this study to improve median male mouse lifespan by 16% and maximum lifespan by 29%, as well as improving physical and mental performance.
Ergothioneine promotes longevity and healthy aging in male mice Full Text

Extra mushroom/ergothioneine studies from March:

Unlocking the Power: New Insights into the Anti-Aging Properties of Mushrooms Full Text

Canadian Content Highlight

In this groundbreaking study, Insilico Medicine, founded by Canadian Alex Zhavoronkov and with one of their sites in Montreal, used AI to generate a target and novel molecule candidate to treat Idiopathic Pulmonary Fibrosis. They reduced the time needed for pre-clinical work from around six years to 18 months! The drug candidate has already passed Phase 1 safety trials and is currently in Phase 2a.

This is not so much about this particular drug, although it also targets several Hallmarks of Aging, it is about the method and its potential to slash the time needed to develop new drugs. As Alex is a long time supporter of longevity, we can be fairly certain that they will also in the future (if not already) use this platform for more specifically longevity focused drugs.
InSilico Shares Details on AI-Generated Drug Candidate Full Text CAN

Supplemental Section

Lifestyle
*Better Life’s Essential 8 contributes to slowing the biological aging process: a cross-sectional study based on NHANES 2007–2010 data Full Text
*Combined effects of sleep and objectively-measured daily physical activity on arterial stiffness in middle-aged and older adults 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.
*Integration of a fasting-mimicking diet programme in primary care for type 2 diabetes reduces the need for medication and improves glycaemic control: a 12-month randomised controlled trial Full Text
*Effect of long-term caloric restriction on telomere length in healthy adults: CALERIE™ 2 trial analysis Full Text
Supplementing probiotics during intermittent fasting proves more effective in restoring ileum and colon tissues in aged rats Full Text

Diet – let food be thy medicine…
*Short-Term Ingestion of Essential Amino Acid Based Nutritional Supplements or Whey Protein Improves the Physical Function of Older Adults Independently of Gut Microbiome Full Text
*Association between dietary inflammatory index and cognitive impairment among American elderly: a cross-sectional study Full Text
*Role of fermented dairy products in the health benefits of a mediterranean diet Full Text

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*Increased frequency of light physical activity during midlife and old age buffers against cognitive declines Full Text
*Daily step count of 9,000 to 10,000 may counteract risk of death and cardiovascular disease in highly sedentary people Full Text
*Do changes in the frailty score differ by the type of group sports and exercises participated in? A 3-year longitudinal study 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.
The Effects of Astaxanthin on Cognitive Function and Neurodegeneration in Humans: A Critical Review Full Text
Astaxanthin targets IL-6 and alleviates the LPS-induced adverse inflammatory response of macrophages 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 in Cancer and Inflammation: An In-Depth Exploration of Molecular Interactions, Therapeutic Potentials, and the Role in Disease Management Full Text
*A systematic review of the efficacy and safety of turmeric in the treatment of digestive disorders Full Text
Enhancing the Bioavailability and Bioactivity of Curcumin for Disease Prevention and Treatment Full Text

Fisetin
Fisetin alleviates cerebral ischemia/reperfusion injury by regulating Sirt1/Foxc1/Ubqln1 pathway-mediated proteostasis

Nicotinamide MonoNucleotide (NMN)
β-Nicotinamide mononucleotide supplementation prolongs the lifespan of prematurely aged mice and protects colon function in ageing mice Full Text
NAD+ precursor supplementation modulates neurite complexity and survival in motor neurons from ALS models

Nicotinamide Riboside (NR)
The mitochondrial UPR induced by ATF5 attenuates intervertebral disc degeneration via cooperating with mitophagy Full Text
Insulin and glycolysis dependency of cardioprotection by nicotinamide riboside Full Text
The Role and Mechanism of Nicotinamide Riboside in Oxidative Damage and a Fibrosis Model of Trabecular Meshwork Cells Full Text

Resveratrol
Resveratrol Shows Potent Senescence Reversal in Experimental Cellular Models of Particular Matter 2.5-induced Cellular Senescence in Human Dermal Papilla Cells Full Text
Unraveling the therapeutic efficacy of resveratrol in Alzheimer’s disease: an umbrella review of systematic evidence Full Text
Resveratrol as a Promising Nutraceutical: Implications in Gut Microbiota Modulation, Inflammatory Disorders, and Colorectal Cancer Full Text

Spermidine
Spermidine treatment: induction of autophagy but also apoptosis? Full Text

Other available supplements or natural substances (in alphabetical order)
Apigenin: a natural molecule at the intersection of sleep and aging Full Text
*Increased nitrate intake from beetroot juice over 4 weeks affects nitrate metabolism, but not vascular function or blood pressure in older adults with hypertension Full Text
Exploring the anti-atherosclerosis mechanism of ginsenoside Rb1 by integrating network pharmacology and experimental verification Full Text
Targeting the Hallmarks of Aging with Vitamin D: Starting to Decode the Myth Full Text
Kaempferol: Paving the path for advanced treatments in aging-related diseases Full Text
*The duration of lithium use and biological ageing: telomere length, frailty, metabolomic age and all-cause mortality Full Text
*Association of taurine intake with changes in physical fitness among community-dwelling middle-aged and older Japanese adults: an 8-year longitudinal study Full Text
Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia Full Text

Combinations of Supplements
The Combined Antioxidant Effects of N-Acetylcysteine, Vitamin D3, and Glutathione from the Intestinal–Neuronal In Vitro Model Full Text
Cardioprotective effect of antioxidant combination therapy: A highlight on MitoQ plus alpha-lipoic acid beneficial impact on myocardial ischemia-reperfusion injury in aged rats Full Text
*A combination nutritional supplement reduces DNA methylation age only in older adults with a raised epigenetic age Full Text
Mitochondrial transplantation combined with coenzyme Q10 induces cardioprotection and mitochondrial improvement in aged male rats with reperfusion injury Full Text

Prescription Supplements

Rapamycin (sirolimus)
A Low Dose of Rapamycin Promotes Hair Cell Differentiation by Enriching SOX2+ Progenitors in the Neonatal Mouse Inner Ear Organoids
Effects of low-dose rapamycin on lymphoid organs of mice prone and resistant to accelerated senescence Full Text
Rapamycin facilitates the tendon-bone interface healing in an aging rat model of chronic rotator cuff injury

Miscellaneous Molecules & Prescription Drugs
*Can a pill (Ca2+ channel blockade) rescue the vascular endothelium from ageing? Full Text
The protective effects of Irbesartan in cognitive impairment in hypertension Full Text
Sitagliptin elevates plasma and CSF incretin levels following oral administration to nonhuman primates: relevance for neurodegenerative disorders Full Text

Novel Molecules
Tetramethylpyrazine Nitrone alleviates D-galactose-induced murine skeletal muscle aging and motor deficits by activating the AMPK signaling pathway Full Text
A Small Molecule to Restore the Liver Full Text
An Experimental Brain Protector May Fight Obesity Full Text

Other Areas of Interest (in alphabetical order)

Ageing Clocks & other biomarkers of ageing
*Clarifying the biological and statistical assumptions of cross-sectional biological age predictors: an elaborate illustration using synthetic and real data Full Text
*Causal association of obesity with epigenetic aging and telomere length: a bidirectional mendelian randomization study Full Text
Integration of polygenic and gut metagenomic risk prediction for common diseases Full Text

Epigenetics & Cellular Reprogramming
Looking for Safety in Epigenetic Rejuvenation Full Text
Multi-omics characterization of partial chemical reprogramming reveals evidence of cell rejuvenation Full Text
Restoration of neuronal progenitors by partial reprogramming in the aged neurogenic niche

Exosomes (small packets of information released by cells)
BMSCs-derived exosomes inhibit macrophage/microglia pyroptosis by increasing autophagy through the miR-21a-5p/PELI1 axis in spinal cord injury Full Text
Extracellular vesicles from human urine-derived stem cells delay aging through the transfer of PLAU and TIMP1 Full Text
Extracellular vesicles derived from mesenchymal stem cells: the wine in Hebe's hands to treat skin aging Full Text

Genetics including CRISPR
Gene therapy approaches for obesity-induced adipose neuropathy: device-targeted AAV-mediated neurotrophic factor delivery to adipocytes in subcutaneous adipose Full Text
*Novel protective effect of the FOXO3 longevity genotype on mechanisms of cellular aging in Okinawans Full Text
Harnessing Genetics to Extend Lifespan and Healthspan: Current Progress and Future Directions Full Text

Lifespan Lengthening Interventions
Lack of telomerase reduces cancer incidence and increases lifespan of zebrafish tp53M214K mutants Full Text
Queen bee gut microbiota extends honeybee lifespan by inhibiting insulin signaling
Elimination of virus-like particles reduces protein aggregation and extends replicative lifespan in Saccharomyces cerevisiae Full Text

Microbiome
Achieving healthy aging through gut microbiota-directed dietary intervention: Focusing on microbial biomarkers and host mechanisms Full Text
*The Interplay between Gut Microbiota and Cognitive Functioning in the Healthy Aging Population: A Systematic Review Full Text
*The interaction between Mediterranean diet and intestinal microbiome: relevance for preventive strategies against frailty in older individuals Full Text

Observational Studies
*Effects from medications on functional biomarkers of aging in three longitudinal studies of aging in Sweden Full Text
*Association between Body Mass Index and Brain Health in Adults: A 16-Year Population-Based Cohort and Mendelian Randomization Study Full Text
*Sleep duration in midlife and old age and risk of mortality over a 48-year follow-up: The Helsinki businessmen study (HBS) cohort Full Text
*U-shaped association between sleep duration and biological aging: Evidence from the UK Biobank study Full Text

Opinion/Editorials/Theory
Timely Yet Long Overdue: Canadian Standards for Long-Term Care Homes Full Text CAN
National Institute on Aging's 50th anniversary: Advancing aging research and the health and well-being of older adults Full Text
Mother’s Curse effects on lifespan and aging Full Text
AagingBase: a comprehensive database of anti-aging peptides Full Text

Other Ageing Biology
Our cells are less likely to express longer genes as we age, researchers say Full Text
Degeneration via Correcting Progerin Mislocalization Full Text
LPD-3 as a megaprotein brake for aging and insulin-mTOR signaling in C. elegans Full Text

Reproductive Health
Multiple treatments with human embryonic stem cell-derived mesenchymal progenitor cells preserved the fertility and ovarian function of perimenopausal mice undergoing natural aging Full Text
Transplantation of the LRP1high subpopulation of human umbilical cord-derived mesenchymal stem cells improves ovarian function in mice with premature ovarian failure and aged mice Full Text
Research Advances in Stem Cell Therapy for Erectile Dysfunction Full Text

Reviews
CAR T therapy from haematological malignancies to aging-related diseases: An ever-expanding universe Full Text
Vascular Aging and Atherosclerosis: A Perspective on Aging Full Text
A Narrative Review Exploring the Similarities between Cilento and the Already Defined “Blue Zones” in Terms of Environment, Nutrition, and Lifestyle: Can Cilento Be Considered an Undefined “Blue Zone”? Full Text

Senolytics/Senescent Cells
Selective targeting of dipeptidyl-peptidase 4 (DPP-4) positive senescent chondrocyte ameliorates osteoarthritis progression Full Text
Repurposing Drugs for Senotherapeutic Effect: Potential Senomorphic Effects of Female Synthetic Hormones Full Text
Natural Senotherapeutics that Mimic Dasatinib Full Text
An in vivo screening platform identifies senolytic compounds that target p16INK4a+ fibroblasts in lung fibrosis Full Text

Skin & Beauty
*Efficacy and Safety of Skin Radiance Collagen on Skin and Hair Matrix: A Placebo-Controlled Clinical Trial in Healthy Human Subjects Full Text
*Oral consumption of Bonito fish-derived elastin peptide (VGPG Elastin®) improves biophysical properties in aging skin: A randomized, double-blinded, placebo-controlled study Full Text
The Potential of Exercise on Lifestyle and Skin Function: Narrative Review Full Text

Stem Cells
Restoring Lymphoid-Myeloid Balance Boosts Immunity in Mice Abstract
The Rejuvenation and Functional Restoration of Aged Adipose Stem Cells by DUXAP10 Knockdown via the Regulation of the miR-214-3p/RASSF5 Axis Full Text
Osteopontin Rejuvenates Senescent Adipose-Derived Stem Cells and Restores their Bone Tissue Regenerative Function Full Text
Mesenchymal stem cells reverse thymus aging by reprogramming the DNA methylation of thymic epithelial cells Full Text

Telomeres
*Efficacy of a dietary supplement derived from five edible plants on telomere length in Thai adults: A randomized, double-blind, placebo-controlled trial Full Text
*Exploring the interplay of psychological and biological components of stress response and telomere length in the transition from middle age to late adulthood: A systematic review Full Text
*Aging Processes Are Affected by Energy Balance: Focused on the Effects of Nutrition and Physical Activity on Telomere Length 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.*
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