November 2023 Longevity Review

This review was a few sentences and an intro away from being finished a few weeks ago before the drama of needing to get a last minute passport derailed my ambitions. I also then used the festive period visiting family in Germany to do a social media/digital/longevity detox for the first time in a number of years. Mea culpa aside, this month’s review is bristling with actionable studies, especially in the diet and exercise sections, which have been expanded to help your motivation for those New Year's resolutions!

In addition, I saw so many studies on sleep and the longevity molecule klotho this month that they both got their own mini-section. Among the other highlights of the supplemental section include using electricity to combat skin senescence, the benefits adding astaxanthin or coffee to exercise, a review of berberine for diabetes and resveratrol for muscle insulin resistance, and the first time I’ve seen a clinical trial brown seaweed for maintaining muscle strength in older humans.

And finally, worth checking out in the opinions section is a novel hypothesis for the ageing of mammals - blame the dinosaurs! Plus of course much more...

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December 2023 Round-Up:

In this intriguing study, researchers used mechanical means to partially reprogram and rejuvenate aged skin cells (75 year old donor), and when implanted into an in vitro human full thickness aged skin model, improved it by increasing production of collagen, elastin and fibronectin - the last two even more than young cells. In addition, the cells also facilitated better wound closure. This mechanical method of reprogramming could be a means of circumventing some of the issues found with current methods.
Mechanically Reprogrammed Fibroblasts for Skin Rejuvenation Full Text

In this study, researchers found a subset of bone marrow derived cells which could help rejuvenate aged blood vessels, and that a substance, pamidronate (PAM), could achieve the same results. Not only that, but PAM also extended the lifespan of both progeroid and naturally aged mice, though the numbers used in the experiments were very small.
CD133+ endothelial-like stem cells restore neovascularization and promote longevity in progeroid and naturally aged mice Full Text

The authors of this study propose and find evidence that there exists a class of cells which fall between normal functioning young and senescent old cells, which they term “Mid-old cells”. These mid-old cells have upregulated pro-inflammatory genes and downregulated anti-inflammatory genes, as well as a general decline in function. They also found that an anti-inflammatory cytokine, SLIT2, which is secreted by young cells, could reverse this, and when injected into old mice, increased muscle mass and how far they could run.
Pre-Senescent Cells May Be Damaging and Treatable Full Text

Originally behind a paywall, this review of longevity related rapamycin clinical trials is now available to all. There are ten trials either ongoing or due to start soon, including the PEARL trial which I helped with the crowdfunding. They should hopefully give us an indication of whether the substantial benefits seen in humans translate to humans.
*Blazing a trail for the clinical use of rapamycin as a geroprotecTOR Full Text (October 2023)

Supplemental Section

Lifestyle
Lifestyle Interventions Against Cellular Senescence Full Text
*Comprehensive lifestyle modification interventions for metabolic syndrome: A systematic review and meta-analysis 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.
*Caloric Restriction Associated With Reduced Senescence Full Text
Aging Might Blunt the Effects of Fasting Full Text
Mechanisms underlying retardation of aging by dietary energy restriction Full Text

Diet – let food be thy medicine…
*New research links high salt consumption to risk of Type 2 diabetes Full Text
*Effect of Dietary Sodium on Blood Pressure Full Text
*Plant-Based Alternatives Are Associated With Less Disease Full Text
*Twin Study: Healthy Vegan Diet Beats Healthy Omnivorous Diet Full Text
*Healthy Diet Linked to Massive Gains in Life Expectancy Full Text

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*Effects of exercise interventions on cognitive functions in healthy populations: A systematic review and meta-analysis Full Text
*Efficacy of morning versus afternoon aerobic exercise training on reducing metabolic syndrome components: A randomized controlled trial Full Text
*Dose-response of accelerometer-measured physical activity, step count, and cancer risk in the UK Biobank: a prospective cohort analysis
*Effect of physical activity on risk of Alzheimer's disease: a systematic review and meta-analysis of twenty-nine prospective cohort studies
*Running Is Associated With Better Health Biomarkers Full Text
*The effect of regular running on body weight and fat tissue of individuals aged 18 to 65 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 Supplementation Augments the Benefits of CrossFit Workouts on Semaphorin 3C and Other Adipokines in Males with Obesity Full Text
Astaxanthin alleviates PM2.5-induced cardiomyocyte injury via inhibiting ferroptosis 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.
*Nano-curcumin effects on nicotine dependence, depression, anxiety and metabolic parameters in smokers: A randomized double-blind clinical study Full Text
*The effect of curcumin supplementation on circulating adiponectin and leptin concentration in adults: A GRADE-assessed systematic review and meta-analysis of randomized controlled trials
*Effects of curcumin/turmeric supplementation on the liver enzymes, lipid profiles, glycemic index, and anthropometric indices in non-alcoholic fatty liver patients: An umbrella meta-analysis

Fisetin
Role of Fisetin in Selected Malignant Neoplasms in Women Full Text
Exploring the therapeutic potential of fisetin: a comprehensive study on its anti-nociceptive and anti-inflammatory effects Full Text
Exploring the underlying mechanisms of fisetin in the treatment of hepatic insulin resistance via network pharmacology and in vitro validation Full Text

Melatonin
*Melatonin supplementation enhances pulmonary rehabilitation outcomes in COPD: A randomized, double-blind, placebo-controlled study

Nicotinamide MonoNucleotide (NMN)
Tumor cell-induced macrophage senescence plays a pivotal role in tumor initiation followed by stable growth in immunocompetent condition Full Text (NMN potentially protective against cancer)
Nicotinamide mononucleotide pretreatment improves long-term isoflurane anesthesia-induced cognitive impairment in mice Full Text

Nicotinamide Riboside (NR)
*A randomized placebo-controlled trial of nicotinamide riboside in older adults with mild cognitive impairment
*NR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson’s disease Full Text

Pterostilbene
Unlocking the therapeutic potential of natural stilbene: Exploring pterostilbene as a powerful ally against aging and cognitive decline

Resveratrol
Resveratrol improves the prognosis of rats after spinal cord injury by inhibiting mitogen-activated protein kinases signaling pathway Full Text
Resveratrol and Its Derivatives in Inflammatory Skin Disorders—Atopic Dermatitis and Psoriasis: A Review Full Text
Resveratrol as a potential protective compound against skeletal muscle insulin resistance Full Text*

Spermidine
*Dietary polyamine intake and all-cause and cause-specific mortality in Japanese adults in the Takayama study Full Text

Other available supplements (in alphabetical order)
Addressing the preventive and therapeutic perspective of berberine against diabetes Full Text
Effect of vitamin D on cardiac hypertrophy in D-galactose-induced aging model through cardiac mitophagy Full Text
*A Combination Study of Pre- and Clinical Trial: Seaweed Consumption Reduces Aging-Associated Muscle Loss Full Text
*N-Acetylcysteine Alleviates the Progression of Chronic Kidney Disease: A Three-Year Cohort Study Full Text
Mitophagy Activation by Urolithin A to Target Muscle Aging Full Text

Combinations of Supplements/Treatments
Vitamin B12-folic acid supplementation improves memory by altering mitochondrial dynamics, dendritic arborization, and neurodegeneration in old and amnesic male mice
The Effect of Glycine and N-Acetylcysteine on Oxidative Stress in the Spinal Cord and Skeletal Muscle After Spinal Cord Injury Full Text
An Evaluation of the Effectiveness of Melatonin and n-Acetylcysteine in Cerebral Ischemia-Reperfusion Injury in Adult Rats Full Text
Tomato and Lemon Extracts Synergistically Improve Cognitive Function by Increasing Brain-derived Neurotrophic Factor Levels in Aged Mice Full Text
Preclinical Studies of Canagliflozin, a Sodium-Glucose Co-Transporter 2 Inhibitor, and Donepezil Combined Therapy in Alzheimer’s Disease Full Text
Aerobic exercise combined with chlorogenic acid exerts neuroprotective effects and reverses cognitive decline in Alzheimer’s disease model mice (APP/PS1) via the SIRT1/ /PGC-1α/PPARγ signaling pathway Full Text (Coffee + exercise)

Prescription Supplements

Metformin
Metformin attenuates inflammation and boosts autophagy in the liver and intestine of chronologically aged rats Full Text
*Effects of metformin therapy on HMGB1 levels in rheumatoid arthritis patients Full Text
The Role and Mechanism of Metformin in Inflammatory Diseases Full Text

Rapamycin (sirolimus)
Therapeutic effect of autophagy induced by rapamycin versus intermittent fasting in animal model of fatty liver Full Text
Inhibition of the mTORC1 pathway alleviates adipose tissue fibrosis Full Text
Endothelial cell-specific reduction in mTOR ameliorates age-related arterial and metabolic dysfunction Full Text (not rapamycin, but its effects should be similar)

Miscellaneous Molecules & Prescription Drugs
Anti–NF-κB peptide derived from nuclear acidic protein attenuates ovariectomy-induced osteoporosis in mice Full Text

Other Areas of Interest (in alphabetical order)

Ageing Clocks & other biomarkers of ageing
*ATAC-clock: An aging clock based on chromatin accessibility Full Text
*ExplaiNAble BioLogical Age (ENABL Age): an artificial intelligence framework for interpretable biological age Full Text
*LensAge index as a deep learning-based biological age for self-monitoring the risks of age-related diseases and mortality Full Text

Epigenetics & Cellular Reprogramming
Mammals Accumulate Epigenetic Noise With Age Full Text
In vivo reprogramming leads to premature death linked to hepatic and intestinal failure

Exosomes (small packets of information released by cells)
A Microvesicle Hydrogel to Treat Arthritis
Microvesicles-hydrogel breaks the cycle of cellular senescence by improving mitochondrial function to treat osteoarthritis Full Text
Plant-derived nanovesicles: harnessing nature's power for tissue protection and repair Full Text
Extracellular Delivery of Functional Mitochondria Rescues the Dysfunction of CD4+ T Cells in Aging Full Text

Genetics including CRISPR
Genetics of human longevity: From variants to genes to pathways Full Text
NeuroD1 administration ameliorated neuroinflammation and boosted neurogenesis in a mouse model of subarachnoid hemorrhage Full Text
Cpt1a silencing in AgRP neurons improves cognitive and physical capacity and promotes healthy aging in male mice Full Text
SIRT2 transgenic over-expression does not impact lifespan in mice Full Text

Klotho Observational Studies
The Longevity Protein Klotho: A Promising Tool to Monitor Lifestyle Improvements Full Text
*L-shaped association of serum α-Klotho and frailty among the middle-aged and older adults: results from NHANES 2007–2016 Full Text
*U-shaped association between serum Klotho and accelerated aging among the middle-aged and elderly US population: a cross-sectional study Full Text
*Relationship between klotho and physical function in healthy aging Full Text

Lifespan Lengthening Interventions
Antibiotics that target mitochondria extend lifespan in C. elegans Full Text
Fermented cereal-origin gerobiotic cocktails promote healthy longevity in Caenorhabditis elegans
Isoleucine Restriction Boosts Lifespan in Mice Abstract

Microbiome
Engraftment of aging-related human gut microbiota and the effect of a seven-species consortium in a pre-clinical model Full Text
Probiotic treatment with Bifidobacterium animalis subsp. lactis LKM512 + arginine improves cognitive flexibility in middle-aged mice Full Text
*Gut microbiome in healthy aging versus those associated with frailty Full Text

Observational Studies
*Social Capital Associates With Better Cognitive Health, Oral Health and Epigenetic Age Deceleration: Findings From the Canadian Longitudinal Study on Aging Full Text
*Self-rated physical health predicts mortality in aging persons beyond objective health risks Full Text
*Improvement of frailty prevalence: difference in factors affecting frailty prevalence among 75 year-old individuals between 2006 and 2019 Full Text

Opinion/Editorials/Theory
Was Mammals’ Longevity Shaped by Living Among Dinosaurs? Full Text
The economics of aging with infectious and chronic diseases

Other Ageing Biology
Parental age effect on the longevity and healthspan in Drosophila melanogaster and Caenorhabditis elegans Full Text
Cartilage tissues regulate systemic aging via ectonucleotide pyrophosphatase/phosphodiesterase 1 in mice Full Text
GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21 Full Text

Regenerative Medicine
'Super melanin' heals skin injuries from sunburn, chemical burns Full Text

Reproductive Health
Cordycepin delays postovulatory aging of oocytes through inhibition of maternal mRNAs degradation via DCP1A polyadenylation suppression Full Text
SIRT6 deficiency causes ovarian hypoplasia by affecting Plod1-related collagen formation Full Text

Reviews
Some HIV-Fighting Drugs May Also Fight Aging Full Text
Mitochondrial-Derived Peptides in Cardiovascular Disease: Novel Insights and Therapeutic Opportunities Full Text
Healthy ageing: Herpes zoster infection and the role of zoster vaccination Full Text
Interventions to Attenuate Cardiovascular Calcification Progression: A Systematic Review of Randomized Clinical Trials Full Text

Senolytics/Senescent Cells
Senolytics May Work Against Long COVID in the Brain Full Text
Current senolytics: mode of action, efficacy and limitations, and their future Full Text
*Translating the Biology of Aging into New Therapeutics for Alzheimer’s Disease: Senolytics Full Text (October 2023) Good summary, also details the results of a clinical trial which was behind a paywall

Skin & Beauty
Electric currents of 448 kHz upregulate anti-senescence pathways in human dermal fibroblasts Full Text
Collagen study advances for photoaging skin Full Text
Human Skin Aging and the Anti-Aging Properties of Retinol Full Text

Sleep Observational Studies
*Sleep regularity and mortality: a prospective analysis in the UK Biobank Full Text
*Daytime napping, biological aging and cognitive function among middle-aged and older Chinese: insights from the China health and retirement longitudinal study Full Text
*Association Between Sleep Traits and Biological Aging Risk: A Mendelian Randomization Study Based on 157,227 Cases and 179,332 Controls

Stem Cells
Mesenchymal Stem Cells in the Pathogenesis and Therapy of Autoimmune and Autoinflammatory Diseases Full Text
The Epigenetic Regulation of Quiescent in Stem Cells Full Text

Telomeres
A novel nutraceutical formulation increases telomere length and activates telomerase activity in middle‑aged rats Full Text
*Can Antidiabetic Medications Affect Telomere Length in Patients with Type 2 Diabetes? A Mini-Review Full Text

Odds & Sods
*Social connectedness, functional capacity, and longevity: A focus on positive relations with others Full Text
*Survival and longevity of European rulers: geographical influences and exploring potential factors, including the Mediterranean diet — a historical analysis from 1354 to the twentieth century 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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