December 2022 Longevity Review

Posted by Chris Pollyanna , 04 January 2023 · 910 views

supplements fasting nad+ nmn rapamycin

As we end another turbulent year, the longevity field thankfully continues to see more steady progress, highlighted by rejuvenated blood stem cells extending lifespan, a new improved epigenetic clock, mole removal via senolytics, and young plasma and microbiomes improving various health parameters.

Meanwhile, in the exercise section, if you’re looking at achievable new year’s goals, you’ll find that even short bouts of vigorous exercise can reduce mortality risk; and in a study inspired by Monty Python, there’s an intriguing new method to increase your energy expenditure whilst walking… Plus of course much more in the rest of the newsletter!

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Chris’s n=1 Rapamycin Trial

I finished my three month rapamycin trial and once again took the AgeRate and GlycanAge tests, which I am now awaiting the results for, though I very much doubt they will show the same improvement my bloodwork showed (lowering of my pheno age from 41 to 35) - fingers crossed!

December 2022 Round-Up:

This study is follow up to a 2020 study showing that CASIN, an inhibitor of a cell regulator which increases with age, significantly increased mouse lifespan. In this new study, just transplanting the blood stem cells of treated mice increased median and maximum lifespan by 24.8% and 34% respectively in the recipients, as well as improving their strength and endurance.
Transplanting rejuvenated blood stem cells extends lifespan of aged immunocompromised mice Full Text

Biological age clocks are not only useful on the individual level to ascertain whether someone is ageing faster or slower than normal, but also, and perhaps more importantly for longevity research, an accurate clock could help speed up future trials by quickly showing if a treatment is working. This study is a further step in that direction, with the latest iteration of the most accurate clock developed so far.
DNA methylation GrimAge version 2 Full Text

As someone who is due to have a few moles removed in the new year, this study caught my eye as the first instance where senolytics, in the form of a skin cream, were used to remove moles from mice. There are obvious implications for the prevention of melanoma.
Targeting anti-apoptotic pathways eliminates senescent melanocytes and leads to nevi regression Full Text

The transfer of young substances, be it plasma or stem cells, to older animals seems to provide benefits and this has now been further extended to the gut microbiome. In this study, microbiome transplantation from young to old mice strengthened their muscles and rejuvenated their skin.
Gut microbiota of the young ameliorates physical fitness of the aged in mice Full Text

After recently focusing a bit more on female reproductive ageing, it’s time to give the men some love: in this study young plasma improved the DNA methylation and sperm counts in the testis of mice.
Young plasma transfer recovers decreased sperm counts and restores epigenetics in aged testis Full Text

2022 was finally the year when a large number of human studies of NMN came out, and it ended with one showing that 600mg per day seemed to provide the most bang for buck in terms of raising NAD+ levels and walking distance. We still need more and larger studies, and in particular meta-analyses, before we truly know the benefit or lack thereof of taking NMN.
*Study Suggests NMN May Improve NAD+ and Walking Speed Full Text

Supplemental Section

Lifestyle
*The power of a healthy lifestyle for cancer prevention: the example of colorectal cancer 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.
*Efficacy and Safety of Intermittent Fasting in People With Insulin-Treated Type 2 Diabetes (INTERFAST-2)—A Randomized Controlled Trial Full Text
*Metabolic effects of alternate-day fasting in males with obesity with or without type 2 diabetes Full Text
Dietary restriction in senolysis and prevention and treatment of disease Full Text

Diet – let food be thy medicine…
*Nutrition, Food and Diet in Health and Longevity: We Eat What We Are Full Text
*Effect of dietary inflammatory potential on the aging acceleration for cardiometabolic disease: A population-based study Full Text
*Associations of dietary flavonoids and subclasses with total and cardiovascular mortality among 369,827 older people: The NIH-AARP Diet and Health Study

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*Short Bouts of Vigorous Activity May Reduce Mortality Risk Full Text
*Quantifying the benefits of inefficient walking: Monty Python inspired laboratory based experimental study Full Text
*Impact of Exercise on Vascular Function in Middle-Aged and Older Adults: A Scoping Review Full Text
*Modular hip exoskeleton improves walking function and reduces sedentary time in community-dwelling 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.
Natural Astaxanthin Is a Green Antioxidant Able to Counteract Lipid Peroxidation and Ferroptotic Cell Death Full Text
Anti-Oxidant and Anti-Inflammatory Effects of Astaxanthin on Gastrointestinal Diseases 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.
*Evaluating the effects of curcumin nanomicelles on clinical outcome and cellular immune responses in critically ill sepsis patients: A randomized, double-blind, and placebo-controlled trial Full Text
*Therapeutic Potential of Curcumin with and without Strengthening Exercises in Improving Rheumatoid Arthritis Full Text

Fisetin
Effects of Fisetin, a Plant-Derived Flavonoid, on Response to Oxidative Stress, Aging, and Age-Related Diseases in Caenorhabditis elegans Full Text
The Potential Role of Fisetin, a Flavonoid in Cancer Prevention and Treatment 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 inhibits ferroptosis and delays age-related cataract by regulating SIRT6/p-Nrf2/GPX4 and SIRT6/NCOA4/FTH1 pathways Full Text
Melatonin as an Antioxidant Agent in Stroke: An Updated Review Full Text

Nicotinamide MonoNucleotide (NMN)
Nicotinamide Mononucleotide Administration Prevents Doxorubicin-Induced Cardiotoxicity and Loss in Physical Activity in Mice Full Text
Modulation of sirtuins during monolayer chondrocyte culture influences cartilage regeneration upon transfer to a 3D culture environment Full Text

Nicotinamide Riboside (NR)
*Oral nicotinamide riboside raises NAD+ and lowers biomarkers of neurodegenerative pathology in plasma extracellular vesicles enriched for neuronal origin Full Text

Pterostilbene
Suppressive effects of pterostilbene on human cytomegalovirus (HCMV) infection and HCMV-induced cellular senescence Full Text

Resveratrol
Resveratrol has its antioxidant and anti-inflammatory protective mechanisms decreased in aging
Preliminary investigation on impact of intergenerational treatment of resveratrol endorses the development of ‘super-pups’

Spermidine
Modulation of histone H3K4 dimethylation by spermidine ameliorates motor neuron survival and neuropathology in a mouse model of ALS Full Text

Other available supplements (in alphabetical order)
*Serum α-Carotene, but Not Other Antioxidants, Is Positively Associated with Muscle Strength in Older Adults: NHANES 2001–2002 Full Text
Roles and Mechanisms of Astragaloside IV in Combating Neuronal Aging Full Text
*Brain vitamin D forms, cognitive decline, and neuropathology in community-dwelling older adults Full Text
SIRT3 activation promotes enteric neurons survival and differentiation Full Text Honokiol
*Effects of fish oil-derived n-3 polyunsaturated fatty acid on body composition, muscle strength and physical performance in older people: a secondary analysis of a randomised, double-blind, placebo-controlled trial
Urolithin A reduces amyloid-beta load and improves cognitive deficits uncorrelated with plaque burden in a mouse model of Alzheimer’s disease Full Text

Combinations of Supplements
The effects of resveratrol and melatonin on biochemical and molecular parameters in diabetic old female rat hearts Full Text
Quercetin and metformin synergistically reverse endothelial dysfunction in the isolated aorta of streptozotocin-nicotinamide- induced diabetic rats Full Text
Combined Effects of Lycopene and Metformin on Decreasing Oxidative Stress by Triggering Endogenous Antioxidant Defenses in Diet-Induced Obese Mice Full Text
*Possible synergic action of non-steroidal anti-inflammatory drugs and glucosamine sulfate for the treatment of knee osteoarthritis: a scoping review Full Text

Prescription Supplements

Metformin
*Metformin in therapeutic applications in human diseases: its mechanism of action and clinical study Full Text
*Causal inference in medical records and complementary systems pharmacology for metformin drug repurposing towards dementia Full Text
*Metformin Acutely Mitigates Oxidative Stress in Human Atrial Tissue: A Pilot Study in Overweight Non-Diabetic Cardiac Patients Full Text

Rapamycin (sirolimus)
Do women age differently from men? Full Text
*Progress on the efficacy and potential mechanisms of rapamycin in the treatment of immune thrombocytopenia Full Text
Rapamycin in the context of Pascal's Wager: generative pre-trained transformer perspective Full Text

Miscellaneous Molecules & Prescription Drugs
17α-estradiol, a lifespan-extending compound, attenuates liver fibrosis by modulating collagen turnover rates in male mice
Acarbose, an α-glucosidase inhibitor, maintains altered redox homeostasis during aging by targeting glucose metabolism in rat erythrocytes
Celecoxib activates autophagy by inhibiting the mTOR signaling pathway and prevents apoptosis in nucleus pulposus cells Full Text
Growth differentiation factor 11: A proangiogenic drug as a potential antiaging regulating molecule
Irisin ameliorates age-associated sarcopenia and metabolic dysfunction Full Text
Irisin ameliorates D-galactose-induced skeletal muscle fibrosis via the PI3K/Akt pathway Full Text
Minocycline Inhibits Microglial Activation and Improves Visual Function in a Chronic Model of Age-Related Retinal Degeneration Full Text
*Rheumatoid arthritis drugs lower risk of heart disease, study shows Full Text

Other Areas of Interest (in alphabetical order)

Ageing Clocks & other biomarkers of ageing
A Targeted Epigenetic Clock for the Prediction of Biological Age Full Text
AnthropoAge, a novel approach to integrate body composition into the estimation of biological age Full Text

Blood Factors or other Heterochronic Transplantation
Aging Affects the Efficacy of Platelet-Rich Plasma Treatment for Osteoarthritis

Epigenetics & Cellular Reprogramming
Single short reprogramming early in life increases healthspan Full Text
A molecular signature defining exercise adaptation with ageing and in vivo partial reprogramming in skeletal muscle

Exosomes (small packets of information released by cells)
Inducible Pluripotent Stem Cell-Derived Small Extracellular Vesicles Rejuvenate Senescent Blood–Brain Barrier to Protect against Ischemic Stroke in Aged Mice
Exosomes derived from human umbilical cord mesenchymal stem cells promote osteogenesis through the AKT signaling pathway in postmenopausal osteoporosis Full Text
Exosomes as a Cell-free Therapy for Myocardial Injury Following Acute Myocardial Infarction or Ischemic Reperfusion Full Text

Genetics including CRISPR
Transcriptome-Wide Organization Changes in Aging Full Text
Gene therapy for heart attacks in mice just got more precise Abstract
Genetic basis of enhanced stress resistance in long-lived mutants highlights key role of innate immunity in determining longevity Full Text
Genetically Enhancing T Cells to Fight Tumors Full Text

Lifespan Lengthening Interventions
Lifespan extension in female mice by early, transient exposure to adult female olfactory cues Full Text
INTERMITTENT KETOGENIC DIETS EXTEND LIFESPAN AND ATTENUATE INFLAMMAGING IN MALE MICE
Soft-Shelled Turtle Peptides Extend Lifespan and Healthspan in Drosophila Full Text
Early life exercise training and inhibition of apoLpp mRNA expression to improve age-related arrhythmias and prolong the average lifespan in Drosophila melanogaster Full Text

Microbiome
*Association between gut microbiota and longevity: a genetic correlation and mendelian randomization study Full Text
Microbiota-immune-brain interactions: A lifespan perspective Full Text
*Evaluation of the efficacy of Lactobacillus-containing feminine hygiene products on vaginal microbiome and genitourinary symptoms in pre- and postmenopausal women: A pilot randomized controlled trial Full Text

Observational Studies
*Musical and multilingual experience are related to healthy aging: better some than none but even better together Full Text
*Study identifies unique set of attributes linked to healthy, optimal aging Full Text
*Cognition, function, and prevalent dementia in centenarians and near-centenarians: An individual participant data (IPD) meta-analysis of 18 studies Full Text
*Who live longer than their age peers: individual predictors of longevity among older individuals Full Text

Opinion/Editorials/Theory
Unveiling the mysteries of senescent cells and their effect on aging and human health
NIH SenNet Consortium to map senescent cells throughout the human lifespan to understand physiological health Full Text
Resolving Geroplasticity to the Balance of Rejuvenins and Geriatrins Full Text
Three Tiers to biological escape velocity: The quest to outwit aging Full Text

Other Ageing Biology
Preferred Migration of Mitochondria toward Cells and Tissues with Mitochondrial Damage Full Text
Downregulation of Sirt6 by CD38 promotes cell senescence and aging Full Text
Sirt6 attenuates chondrocyte senescence and osteoarthritis progression Full Text
Molecular and spatial signatures of mouse brain aging at single-cell resolution Full Text

Reproductive Health
Hyperbaric Oxygen Treatment Ameliorates the Decline in Oocyte Quality and Improves the Fertility of Aged Female Mice Full Text
Resveratrol and SIRT1: Antiaging Cornerstones for Oocytes? Full Text
Intermittent fasting reverses the declining quality of aged oocytes

Reviews
Role of angiotensin II in aging Full Text
Hyperbaric Oxygen Therapy and Tissue Regeneration: A Literature Survey Full Text
Role of autophagy in aging: The good, the bad, and the ugly Full Text

Senolytics/Senescent Cells
Senescence atlas reveals an aged-like inflamed niche that blunts muscle regeneration Full Text
Senolytic treatment preserves biliary regenerative capacity lost through cellular senescence during cold storage Full Text
Eliminating Senescent Cells Can Promote Pulmonary Hypertension Development and Progression Full Text

Skin & Beauty
*The Clinical Evidence-Based Paradigm of Topical Anti-Aging Skincare Formulations Enriched with Bio-Active Peptide SA1-III (KP1) as Collagen Modulator: From Bench to Bedside Full Text
*A long term study of the difference in efficacy and effect rate of various concentrations of retinol (1500-6600 IU) in middle aged women
Phytocannabinoids Stimulate Rejuvenation and Prevent Cellular Senescence in Human Dermal Fibroblasts Full Text

Stem Cells
*Ex vivo manufacturing of platelets: beyond the first-in-human clinical trial using autologous iPSC-platelets Full Text
Stem Cell Transplantation for Parkinson’s Disease: Current Challenges and Perspectives Full Text
Transplantation of bone marrow-derived mesenchymal stem cells ameliorated dopamine system impairment in a D-galactose-induced brain ageing in rats 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 *bolded any human trials.*
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