January 2023 Longevity Review

The start of a new year marks not only new beginnings, but also that we are one year closer to effective longevity treatments. However, not wishing perfection to be the enemy of good, there is plenty we can do in the meantime, as this month’s Round-Up shows. You’ll find a combination of supplements potentially helping with Alzheimer’s, two other drugs reducing mortality, while another increased the health and lifespan of older mice - and that’s not including the other treasures to be found in the supplemental section.
For the CLA, 2023 should also be a significant year of progress with a number of notable announcements forthcoming, starting with the unveiling of our Discord server this month (check below for details). Exciting times lie ahead!

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CLA News

January saw a ramping up of CLA activity with the highlight being the stellar work of our volunteers, Bryan & Myles, in putting together our very own public community Discord server, which I am here humbly inviting you to join!

CLA Discord Invite Link

Not only will you find links to all of our social media output, from Facebook to YouTube, but it will also hopefully provide a better environment for discussion. Additionally, it provides another means of contacting us and finding out more about the CLA.

January 2023 Round-Up:

This four drug combination treatment, consisting of L-serine, NR, NAC & L-carnitine, significantly improved ADAS-cog scores and brain metabolite & protein profiles in Alzheimer's disease. In addition, NAD+ and glutathione levels were improved and hippocampal volume was maintained. This combination was also associated with a reduction in COVID recovery times in 2021. The usual caveat applies that this was a small phase 2 trial and that larger phase 3 trials need to take place.
*Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial Full Text

In the first of two observational studies, lithium was shown to reduce mortality 3.6 fold among UK Biobank participants taking anti-psychotic medication. This ties in well with studies showing an inverse correlation between lithium levels in drinking water and mortality, as well as improvements in mouse healthspan.
*Lithium treatment extends human lifespan: findings from the UK Biobank Full Text

In this second observational study, men with ED who took PDE-5 inhibitors (e.g. Viagra) had a 13% reduction in major adverse cardiovascular events and 25% reduction in overall mortality compared to the matched controls. The mortality reduction was further increased to almost 50% between the top and bottom quartiles of users.
*Effect of phosphodiesterase type 5 inhibitors on major adverse cardiovascular events and overall mortality in a large nationwide cohort of men with erectile dysfunction and cardiovascular risk factors: A retrospective, observational study based on healthcare claims and national death index data Full Text

This study showed that genistein, found in soybeans, extended the mean and maximum lifespan of male mice by 10% and 9% respectively. More impressively, the mice only started taking genistein from 18 months of age. Furthermore, inflammatory signals and gut dysfunction were reduced with an improvement in the gut microbiota and frailty index. This follows on from signs of benefit against Alzheimer’s in a recent human study.
Dietary genistein increases microbiota-derived short chain fatty acid levels, modulates homeostasis of the aging gut, and extends healthspan and lifespan Full Text

The original Hallmarks of Aging paper from 2013 is the most cited paper in the longevity field, and here, the same authors offer an updated and expanded version with three new hallmarks: chronic inflammation, disabled macroautophagy, and dysbiosis. Unfortunately, it is behind a paywall, but you can read the Lifespan.io analysis:
The Hallmarks of Aging’s Original Authors Offer a Fresh View Abstract

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.
*Reducing total calories may be more effective for weight loss than intermittent fasting Full Text
*Effect of Time-Restricted Eating and Resistance Training on High-Speed Strength and Body Composition Full Text
Gut Microbiota and Time-Restricted Feeding/Eating: A Targeted Biomarker and Approach in Precision Nutrition Full Text
Caloric restriction induced epigenetic effects on aging Full Text

Diet – let food be thy medicine…
*Adherence to a Mediterranean Diet for 6 Months Improves the Dietary Inflammatory Index in a Western Population: Results from the MedLey Study Full Text
*Mediterranean Diet, Ketogenic Diet or MIND Diet for Aging Populations with Cognitive Decline: A Systematic Review Full Text
*Association between dietary inflammatory index and cognitive impairment: A meta-analysis Full Text

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*Tissue-specific effects of exercise as NAD+-boosting strategy: Current knowledge and future perspectives Full Text
*Effect of High-Intensity Interval Training on Functional Movement in Older Adults: A Systematic Review and Meta-analysis Full Text
*Effects of exercise training on metabolic syndrome risk factors in post-menopausal women – A systematic review and meta-analysis of randomised controlled trials 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 Supplemented with High-Intensity Functional Training Decreases Adipokines Levels and Cardiovascular Risk Factors in Men with Obesity Full Text
Astaxanthin: A promising therapeutic agent for organ fibrosis Full Text
Astaxanthin attenuates cigarette smoking-induced oxidative stress and inflammation in a sirtuin 1-dependent manner 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.
*Profiling Inflammatory Biomarkers following Curcumin Supplementation: An Umbrella Meta-Analysis of Randomized Clinical Trials Full Text
*Is Curcumine Useful in the Treatment and Prevention of the Tendinopathy and Myotendinous Junction Injury? A Scoping Review Full Text
Multiple mechanisms of curcumin targeting spinal cord injury Full Text

Fisetin
Fisetin alleviates cellular senescence through PTEN mediated inhibition of PKCδ-NOX1 pathway in vascular smooth muscle cells

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.
*Current Insights into the Risks of Using Melatonin as a Treatment for Sleep Disorders in Older Adults Full Text
Melatonin inhibits atherosclerosis progression via galectin-3 downregulation to enhance autophagy and inhibit inflammation Full Text
Protective effect of melatonin on learning and memory impairment and hippocampal dysfunction in rats induced by high-fructose corn syrup Full Text

Nicotinamide MonoNucleotide (NMN)
NMN Alleviates Silicate Lung Injury in Mice Full Text (Dec 2022)
NMN: The NAD Precursor at the Intersection Between Axon Degeneration and Anti-ageing Therapies Full Text
NMN Reduces Metastasis in Difficult Breast Cancer Model Abstract

Nicotinamide Riboside (NR)
*Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study Full Text

Resveratrol
*The effect of resveratrol supplementation on biomarkers of liver health: A systematic review and meta-analysis of randomized controlled trials
Effects of Resveratrol on Muscle Inflammation, Energy Utilisation, and Exercise Performance in an Eccentric Contraction Exercise Mouse Model Full Text

Spermidine
Effect of spermidine on radiation-induced long-term bone marrow cell injury Full Text

Other available supplements (in alphabetical order)
*Effects of Vitamin D Supplementation on Testosterone, Prostate, and Lower Urinary Tract Symptoms: A Prospective, Comparative Study Full Text
Genistein Promotes Anti-Heat Stress and Antioxidant Effects via the Coordinated Regulation of IIS, HSP, MAPK, DR, and Mitochondrial Pathways in Caenorhabditis elegans Full Text
*Higher Dietary Vitamin K Intake is Associated with Better Physical Function and Lower Long-Term Injurious Falls Risk in Community-Dwelling Older Women Full Text
*New perspectives on randomized controlled trials with omega-3 fatty acid supplements and cognition: a scoping review Full Text
*Association of omega 3 polyunsaturated fatty acids with incident chronic kidney disease: pooled analysis of 19 cohorts Full Text
*Royal Jelly Increases Hematopoietic Stem Cells in Peripheral Blood: A Double-Blind, Placebo-Controlled, Randomized Trial in Healthy Subjects Full Text

Combinations of Supplements
*Safety and efficacy of combined resveratrol and sirolimus in lymphangioleiomyomatosis
*Effects of a Polypill, Aspirin, and the Combination of Both on Cognitive and Functional Outcomes Full Text
Effect of Sirolimus/Metformin Co-Treatment on Hyperglycemia and Cellular Respiration in BALB/c Mice Full Text
Potential Synergistic Supplementation of NAD+ Promoting Compounds as a Strategy for Increasing Healthspan Full Text

Prescription Supplements

Metformin
*Metabolic modelling of the human gut microbiome in type 2 diabetes patients in response to metformin treatment Full Text
Metformin and Its Immune-Mediated Effects in Various Diseases Full Text

Rapamycin (sirolimus)
Molecular and therapeutic insights of rapamycin: a multi-faceted drug from Streptomyces hygroscopicus Full Text
*TORing the impact of sirolimus on immune health Full Text
*Response to sirolimus in capillary lymphatic venous malformations and associated syndromes: Impact on symptomatology, quality of life, and radiographic response Full Text

Miscellaneous Molecules & Prescription Drugs
Osteocalcin inhibits myocyte aging through promotion of starvation-induced autophagy via IL-6/STAT3 signaling Full Text
Hydralazine Revives Cellular and Ocular Lens Health-Span by Ameliorating the Aging and Oxidative-Dependent Loss of the Nrf2-Activated Cellular Stress Response Full Text
Teriflunomide as a therapeutic means for myelin repair Full Text

Other Areas of Interest (in alphabetical order)

Ageing Clocks & other biomarkers of ageing
Cross-sectionally calculated metabolic ageing does not relate to longitudinal metabolic changes – support for stratified ageing models Full Text
*Mortality associations with DNA methylation-based biological aging and physical functioning measures across a 20-year follow-up period Full Text
*Alcohol consumption and epigenetic age acceleration in young adults Full Text

Blood Factors or other Heterochronic Transplantation
Blood-to-brain communication in aging and rejuvenation Full Text
Mitotherapy restores hippocampal mitochondrial function and cognitive impairment in aged male rats subjected to chronic mild stress

Epigenetics & Cellular Reprogramming
STAT3 promotes a youthful epigenetic state in articular chondrocytes Full Text
David Sinclair: Epigenetic Info Loss Is a Cause of Aging Abstract

Exosomes (small packets of information released by cells)
NAMPT encapsulated by extracellular vesicles from young adipose-derived mesenchymal stem cells treated tendinopathy in a “One-Stone-Two-Birds” manner Full Text
The Double-Edged Role of Extracellular Vesicles in the Hallmarks of Aging Full Text
Exosome Release Delays Senescence by Disposing of Obsolete Biomolecules Full Text

Genetics including CRISPR
Anti-Aging Gene Shown To Rewind Heart Age by 10 Years Full Text
Convergent genomics of longevity in rockfishes highlights the genetics of human life span variation Full Text
Current Trends and Approaches to the Search for Genetic Determinants of Aging and Longevity Full Text (Dec 2022)
Correlated evolution of social organization and lifespan in mammals Full Text

Lifespan Lengthening Interventions
Scientists identify drug that could extend lifespan Abstract
Rilmenidine extends lifespan and healthspan in Caenorhabditis elegans via a nischarin I1-imidazoline receptor Full Text
The metabolite alpha-ketobutyrate extends lifespan by promoting peroxisomal function in C. elegans Full Text
Cell-cell metabolite exchange creates a pro-survival metabolic environment that extends lifespan Full Text

Microbiome
*Development of a lactic acid bacteria strain that suppresses chronic inflammation and improves glucose and lipid metabolism Full Text
Fermented Supernatants of Lactobacillus plantarum GKM3 and Bifidobacterium lactis GKK2 Protect against Protein Glycation and Inhibit Glycated Protein Ligation Full Text
Bifidobacterium longum supplementation improves age-related delays in fracture repair Full Text

Observational Studies
*Frailty trajectories and associated factors in the years prior to death: evidence from 14 countries in the Survey of Health, Aging and Retirement in Europe Full Text
*Plasma inflammation-related biomarkers are associated with intrinsic capacity in community-dwelling older adults Full Text
*Virus exposure and neurodegenerative disease risk across national biobanks Full Text

Opinion/Editorials/Theory
Are menopause, aging and prostate cancer diseases? Full Text
Evolution of Longevity as a Species-Specific Trait in Mammals Full Text
Is Aging an Inevitable Characteristic of Organic Life or an Evolutionary Adaptation? Full Text

Other Ageing Biology
Questioning the Usefulness of Model Organisms Abstract
Age-related matrix stiffening epigenetically regulates α-Klotho expression and compromises chondrocyte integrity Full Text
Reduced sphingolipid biosynthesis modulates proteostasis networks to enhance longevity Full Text
Interactomics: dozens of viruses, co-evolving with humans, including the influenza A virus, may actively distort human ageing Full Text

Reproductive Health
*The Effect of Testosterone Replacement on Sexual Function in the Elderly: A Systematic Review and Meta-Analysis Full Text
Bone Marrow Mesenchymal Stem Cells Reversed Ovarian Aging-related m6A RNA Methylation Modification Profile in Aged Granulosa Cells Full Text
Increased cellular senescence in doxorubicin-induced murine ovarian injury: effect of senolytics Full Text

Reviews
Mitochondria-derived peptide MOTS-c: effects and mechanisms related to stress, metabolism and aging Full Text
Concepts and definitions of healthy ageing: a systematic review and synthesis of theoretical models Full Text
The impact of blue light and digital screens on the skin Full Text

Senolytics/Senescent Cells
Reversine ameliorates hallmarks of cellular senescence in human skeletal myoblasts via reactivation of autophagy Full Text
Senolytic Improves Metabolism in Mice Full Text
Functional restoration of lysosomes and mitochondria through modulation of AKT activity ameliorates senescence Full Text
Reduction in Lens Epithelial Cell Senescence Burden through Dasatinib Plus Quercetin or Rapamycin Alleviates D-Galactose-Induced Cataract Progression Full Text (Dec 2022)

Skin & Beauty
*Topical Lactiplantibacillus plantarum LB244R® ointment alleviates skin aging: An exploratory trial Full Text
New Way to Help Aging Cells Produce Collagen Full Text
Anagen hair follicles transplanted into mature human scars remodel fibrotic tissue Full Text

Stem Cells
*Comparative effectiveness of adipose-derived mesenchymal stromal cells in the management of knee osteoarthritis: A meta-analysis Full Text
Very small embryonic-like stem cells have the potential to win the three-front war on tissue damage, cancer, and aging Full Text

Telomeres
*No strong association among epigenetic modifications by DNA methylation, telomere length, and physical fitness in biological aging Full Text
*Does oxidative stress shorten telomeres in vivo? A meta-analysis Full Text
*Associations of green tea, coffee, and soft drink consumption with longitudinal changes in leukocyte telomere length Full Text

Odds & Sods
Galactic cosmic radiation exposure causes multifaceted neurocognitive impairments Full Text
Functional T cells are capable of supernumerary cell division and longevity Full Text
*Home-based transcranial direct current stimulation in mild neurocognitive disorder due to possible Alzheimer’s disease. A randomised, single-blind, controlled-placebo study 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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