September 2023 Longevity Review

Posted by Chris Pollyanna , 01 November 2023 · 786 views

supplements lifestyle nad+ nmn rapamycin resveratrol fasting senolytics exosomes

Welcome to another Longevity Review. The highlights this month include gene therapy for memory enhancement, exosomes for osteoarthritis, senolytics to regenerate the small intestine, NMN for blood pressure, and how it is never too late to start exercising.
In the supplemental section, there was another human trial result for senolytics, this time in Alzheimer’s, which showed that D & Q were safe to be used in that context. In addition, there are a couple quirky papers in the Opinion and Lifespan sections, one looking at immortality for AI and the other looking at using ethanol to produce a similar outcome in worms! Plus of course much more…

CLA News
September saw the start of our outreach activities and during the course of the month the CLA attended two events, one, a networking event by Life Sciences Ontario, and the other an introduction to longevity event at the University of Toronto. Some useful connections were made at the LSO event, while the UofT event resulted in meeting some new future collaborators, in the form of a student longevity group, and us getting a new volunteer - a big warm welcome to Ashley!

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September 2023 Round-Up:

Using gene therapy to increase the amount of a protein (GNAQ) in the brain resulted in improved long term memory for both older worms and mice. In worms, it tripled their memory span, while in mice, it led to the oldest age (24 months) at which long term memory was able to be improved - the equivalent of 70 to 80 year old humans.
A Mutation Improves Lifelong Memory in Worms and Mice Full Text

Here are two papers which demonstrate the potential of exosomes for the treatment of osteoarthritis (OA), with the first showing that they reduced inflammatory markers in cells, and the second indicating they reduced OA progression in rats. Using exosomes would be a lot safer than stem cells for this condition.
Developing a Treatment for Arthritis from Stem Cell Signals Full Text
Exosomes Derived from Hypoxia-Cultured Human Adipose Stem Cells Alleviate Articular Chondrocyte Inflammaging and Post-Traumatic Osteoarthritis Progression Full Text

In this paper, researchers showed for the first time that senolytics are effective in the small intestine. Using D+Q in an older mouse model, senescent cells decreased while the structure improved with increased progenitor cells. In humans this should lead to improved nutrient absorption, which declines with age and causes malnutrition.
Senolytic Treatment Improve Small Intestine Regeneration in Aging Full Text

The popular supplement NMN was shown to reduce blood pressure in this very small clinical study. A six week course of 800mg reduced systolic and diastolic blood pressure by 6.11 & 3.56 mmHg respectively and improved vascular function measured by flow mediated dilation and pulse wave velocity.
*NMN Reduces Systolic Blood Pressure in Clinical Trial Full Text

Use it or lose it, but it’s never too late to start, at least according to this study which took sedentary older men (72 years old) and put them into an exercise program. Compared to those who remained sedentary and also their former selves, the exercisers significantly improved their fitness levels, which remained elevated for the four years of the study. Those who didn’t exercise saw their fitness levels continue to decline.
*Taking Up Exercise Late in Life May Prevent Fitness Decline Full Text

Supplemental Section

Lifestyle
*Life’s Essential 8: Optimizing Health in Older Adults Full Text
*Association between life’s essential 8 and biological ageing among US adults Full Text
*Profiles of lifestyle health behaviors and cognitive decline in 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.
*Bio-Hacking Better Health—Leveraging Metabolic Biochemistry to Maximise Healthspan Full Text
*A single 36-h water-only fast vastly remodels the plasma lipidome Full Text
Effect of dietary restriction on health span in Caenorhabditis elegans: A systematic review Full Text

Diet – let food be thy medicine…
*Inverse J-Shaped Relationship of Dietary Carbohydrate Intake with Serum Klotho in NHANES 2007–2016 Full Text
*The Effects of Flavonoids on Skeletal Muscle Mass, Muscle Function, and Physical Performance in Individuals with Sarcopenia: A Systematic Review of Randomized Controlled Trials Full Text
*Effects of Plant-Based Protein Interventions, with and without an Exercise Component, on Body Composition, Strength and Physical Function in Older Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials Full Text

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*Effect of Hypoxia Conditioning on Body Composition in Middle-Aged and Older Adults: A Systematic Review and Meta-Analysis Full Text
*Adherence to aerobic training combined with high protein intake is associated with low blood pressure in Italian older adults: a cross-sectional study Full Text
*Relationship of Daily Step Counts to All-Cause Mortality and Cardiovascular Events

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 attenuates cognitive deficits in Alzheimer’s disease models by reducing oxidative stress via the SIRT1/PGC-1α signaling pathway Full Text
Astaxanthin ameliorates dopaminergic neuron damage in paraquat-induced SH-SY5Y cells and mouse models of Parkinson's disease Full Text
Astaxanthin attenuated cigarette smoke extract-induced apoptosis via decreasing oxidative DNA damage in airway epithelium 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.
Protective effects of curcumin against osteoporosis and its molecular mechanisms: a recent review in preclinical trials Full Text
*Effects of curcumin/turmeric supplementation on glycemic indices in adults: A grade-assessed systematic review and dose-response meta-analysis of randomized controlled trials

Fisetin
Fisetin—In Search of Better Bioavailability—From Macro to Nano Modifications: A Review Full Text
Evaluation of the anti-inflammatory activity of fisetin-loaded nanoparticles in an in vitro model of osteoarthritis Full Text
Fisetin, a potential skin rejuvenation drug that eliminates senescent cells in the dermis

Melatonin
Melatonin as a therapeutic agent for alleviating endothelial dysfunction in cardiovascular diseases: Emphasis on oxidative stress Full Text

Nicotinamide MonoNucleotide (NMN)
NAD+ rescues aging-induced blood-brain barrier damage via the CX43-PARP1 axis (Aug 2023)
Temperature-sensitive hydrogel dressing loaded with nicotinamide mononucleotide accelerating wound healing in diabetic mice Full Text

Nicotinamide Riboside (NR)
Epithelial NAD+ depletion drives mitochondrial dysfunction and contributes to intestinal inflammation Full Text

Pterostilbene
Pterostilbene exerts cytotoxicity on activated hepatic stellate cells by inhibiting excessive proliferation through the crosstalk of Sirt1 and STAT3 pathways

Resveratrol
Potential Therapeutic Targets of Resveratrol in the Prevention and Treatment of Pulmonary Fibrosis Full Text
*Integrative evidence construction for resveratrol treatment of nonalcoholic fatty liver disease: preclinical and clinical meta-analyses Full Text
Quality of systematic reviews with meta-analyses of resveratrol: A methodological systematic review

Other available supplements (in alphabetical order)
*The Effects of Combined Exercise with Citrulline Supplementation on Body Composition and Lower Limb Function of Overweight Older Adults: A Systematic Review and Meta-Analysis Full Text
*Effectiveness of Creatine in Metabolic Performance: A Systematic Review and Meta-Analysis Full Text
*Oral supplementation with fish cartilage hydrolysate in an adult population suffering from knee pain and function discomfort: results from an innovative approach combining an exploratory clinical study and an ex vivo clinical investigation Full Text
*Effects of N-acetylcysteine on aging cell and obesity complications in obese adults: a randomized, double-blind clinical trial Full Text
*Correlations Between Omega-3 Fatty Acids and Brain Function Full Text

Combinations
Synergistic effects of MFG-E8 and whey protein on mitigating D-galactose-induced sarcopenia through PI3K/AKT/PGC-1α and MAPK/ERK signaling pathways Full Text
*Novel Multi-Ingredient Supplement Facilitates Weight Loss and Improves Body Composition in Overweight and Obese Individuals: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial Full Text (Aug 2023) can
Metformin combined with rapamycin ameliorates podocyte injury in idiopathic membranous nephropathy through the AMPK/mTOR signaling pathway Full Text

Prescription Supplements

Metformin
*Cell-type specific impact of metformin on monocyte epigenetic age reversal in virally suppressed older people living with HIV Full Text
*Comparing the effectiveness of metformin with lifestyle modification for the primary prevention of type II diabetes: a systematic review and meta-analysis Full Text
*No association between metformin initiation and incident dementia in older adults newly diagnosed with diabetes Full Text

Rapamycin (sirolimus)
The Long Scientific Journey of Sirolimus (Rapamycin): From the Soil of Easter Island (Rapa Nui) to Applied Research and Clinical Trials on β-Thalassemia and Other Hemoglobinopathies Full Text
Pre-clinical investigation of liquid sirolimus for local drug delivery Full Text

Miscellaneous Molecules & Prescription Drugs
Atorvastatin rescues hyperhomocysteinemia-induced cognitive deficits and neuroinflammatory gene changes Full Text
How Does It Work? Unraveling the Mysteries by Which Empagliflozin Helps Diabetic and Non-diabetic Patients With Heart Failure Full Text
Immunomodulatory Effects of SGLT2 Inhibitors—Targeting Inflammation and Oxidative Stress in Aging Full Text (Aug 2023)
Current evidence for J147 as a potential therapeutic agent in nervous system disease: a narrative review Full Text
PDE5 inhibitor drugs for use in dementia Full Text

Other Areas of Interest (in alphabetical order)

Ageing Clocks & other biomarkers of ageing
Aging Rate Indicators: Speedometers for Aging Research in Mice Full Text
Creating a Noise Clock to Measure Biological Age Full Text
*Association of biological age with health outcomes and its modifiable factors Full Text
*Sex differences in biological aging and the association with clinical measures in older adults Full Text

Blood Factors or other Heterochronic Transplantation
*Late-life plasma proteins associated with prevalent and incident frailty: A proteomic analysis Full Text

Epigenetics & Cellular Reprogramming
Reprogramming endothelial and vascular smooth muscle cells to prevent and treat hypertension

Exosomes (small packets of information released by cells)
Mesenchymal-derived extracellular vesicles enhance microglia-mediated synapse remodeling after cortical injury in aging Rhesus monkeys Full Text

Genetics including CRISPR
Geroprotective interventions converge on gene expression programs of reduced inflammation and restored fatty acid metabolism Full Text
Open Genes—a new comprehensive database of human genes associated with aging and longevity Full Text
*Genes Involved in DNA Damage Cell Pathways and Health of the Oldest-Old (85+) Full Text
SIRT2 Works Against Cardiac Aging in Mice and Monkeys Abstract

Lifespan Lengthening Interventions
Periodic ethanol supply as a path toward unlimited lifespan of Caenorhabditis elegans dauer larvae Full Text
Protein restriction effects on health-span and lifespan in Drosophila melanogaster are additive with a longevity-promoting diet Full Text
Global analysis of aging-related protein structural changes uncovers enzyme-polymerization-based control of longevity Full Text
Salidroside promotes healthy longevity by interfering with HSP90 activity
Neuronal mTORC1 inhibition promotes longevity without suppressing anabolic growth and reproduction in C. elegans Full Text

Microbiome
*Resistant starch supplement reduces liver triglycerides in people with fatty liver disease Full Text
The Potential Role of Probiotics in the Management of Osteoarthritis Pain: Current Status and Future Prospects Full Text
Psychobiotics for Mitigation of Neuro-Degenerative Diseases: Recent Advancements Full Text

Observational Studies
*Treating Hypertension May Reduce Dementia Risk Full Text
*Gains in life expectancy from decreasing cardiovascular disease and cancer mortality – an analysis of 28 european countries 1995–2019 Full Text
*Blood Biomarkers as Predictors of Longevity
*Blood biomarker profiles and exceptional longevity: comparison of centenarians and non-centenarians in a 35-year follow-up of the Swedish AMORIS cohort Full Text
*Study: Waist-to-Hip Ratio Predicts Mortality Better Than BMI Full Text

Opinion/Editorials/Theory
Is There a Single Essence of Aging? Full Text
A Poisson distribution-based general model of cancer rates and a cancer risk-dependent theory of aging Full Text
Two Industries in One Field - Snake oil and real science are entirely different Full Text
Hormesis defines the limits of lifespan Full Text
Synthesizing Methuselah: The Question of Artificial Agelessness Full Text

Other Ageing Biology
Autophagy Receptor-Inspired Antibody-Fusion Proteins for Targeted Intracellular Degradation Full Text
*Modelling lifespan reduction in an exogenous damage model of generic disease Full Text

Reproductive Health
*Review of over 70 years of menopause science highlights research gaps and calls for individualized treatment Full Text
*The Effectiveness of Pelvic Floor Muscle Exercise in Urinary Incontinence: A Systematic Literature Review and Meta-Analysis Full Text
*Menopause age, reproductive span and hormone therapy duration predict the volume of medial temporal lobe brain structures in postmenopausal women Full Text
Buck Researchers Uncover Mechanism That Links NAD+ to Fertility Problems Full Text

Reviews
How Pollution Makes Aging Worse Full Text
Proteostasis in T cell aging Full Text
Alteration in the chromatin landscape during the DNA damage response: Continuous rotation of the gear driving cellular senescence and aging Full Text

Senolytics/Senescent Cells
*Senolytic therapy in mild Alzheimer’s disease: a phase 1 feasibility trial
*Mixed Results With Senolytic Agent for Retinal Disease (Aug 2023)
A novel BRD4 degrader, ARV-825, attenuates lung fibrosis through senolysis and antifibrotic effect
Senescent cells at the crossroads of aging, disease, and tissue homeostasis Full Text

Skin & Beauty
*Antiaging effects of a skin care formulation containing nanoencapsulated antioxidants: A clinical, in vitro, and ex vivo study Full Text
Therapeutic potential of adipose tissue derivatives in skin photoaging Full Text
High-Intensity Focused Ultrasound Increases Collagen and Elastin Fiber Synthesis by Modulating Caveolin-1 in Aging Skin Full Text

Stem Cells
The Role of Box A of HMGB1 in Enhancing Stem Cell Properties of Human Mesenchymal Cells: A Novel Approach for the Pursuit of Anti-aging Therapy Full Text
Improving Quality and Length of Life with Stem Cells Full Text

Telomeres
*Telomere length as a marker of changes in body composition and fractures-an analysis of data from the NHANES 2001-2002 Full Text
Distinct roles of telomerase activity in age-related chronic diseases: An update literature review Full Text
Low Antioxidant Glutathione Levels Lead to Longer Telomeres: A Sex-Specific Link to Longevity? 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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