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December 2024 Longevity Review
supplements gene therapy telomeres senolytics microbiome probiotics extracellular vesicles
Hello and welcome to the final longevity review of 2024. This month we will take a look at gene therapy to increase telomere length; freeing the immune system to remove senescent cells; using probiotics to help with sarcopenia; and, in the Canadian content study, employing extracellular vesicles to deliver drugs to the brain to combat neuroinflammation.
In the Supplemental Section, you’ll find in Lifestyle how exercise and sleep improve memory the next day; in Diet, how moderate wine consumption can lower CVD risk, and how a well-balanced vegan diet can stimulate protein production as much as an omnivorous diet; in Exercise, a systematic review on HIIT and cognition; in Curcumin, a systematic review of its effects on exercise; in Miscellaneous Molecules, a systematic review of anti-diabetic medication’s anti-dementia benefits; in Novel Molecules, another AI generated drug; in Blood Factors, umbilical cord blood infusions helped with AML; in Exosomes, a review of their application in aging related diseases; in Genetics, gene therapy for hearing loss; in Observational, how intrinsic capacity in old age is greater in later born birth cohorts; in Other, RANKL treatment can restore the thymus; in Reproduction, berberine promotes aged fertility; in Senolytics, ABT-263 for aged skiing and wound healing; and, in Stem Cells, a review of their effectiveness for osteoarthritis.
(To make these suggestions easier to find, I’ve marked them with ***)
Canadian Longevity Association News
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We also have big plans for 2025, which will be revealed in due course - so watch this space!
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December 2024 Highlights:
In this study, the potential of using gene therapy to extend telomere length was examined. Telomeres shorten with age and previous studies have shown that lengthening them can improve lifespan and other health benefits. Although the type of gene therapy used couldn’t be used in humans, the results nonetheless impressive, with one group of mice having an almost 50% increase in lifespan, which is the largest increase in mouse lifespan that I have seen. In addition, they showed great regenerative potential with improved skin wound healing and recovery from induced colitis.
Telomerase reverse transcriptase gene knock-in unleashes enhanced longevity and accelerated damage repair in mice Full Text
Senolytics (the removal of senescent, or zombie cells) have been in development for some time and have mainly focused on killing the cells directly by using molecules to have them commit suicide or engineering CAR-T cells to remove them. However, the immune system should be clearing senescent cells on its own, and that is what the researchers here have developed, by targeting a molecule (ganglioside GD3) on the surface of senescent cells which was hiding them from the immune system. Once removed, natural killer cells homed in on them and removed them. This could be a more selective and natural way of removing senescent cells.
A ganglioside-based immune checkpoint enables senescent cells to evade immunosurveillance during aging Full Text
In this study in both mice and sarcopenic humans (sarcopenia is the debilitating loss of muscle function with age), a probiotic containing a strain of Bifidobacterium animalis was able to improve muscle function and physical performance. It also changed the gut microbiota and their metabolites in a beneficial direction, and raised levels of creatine, which is important for muscles. It should be noted that there was no placebo control in the human study, but if larger placebo controlled studies are successfully carried out, then this could be an inexpensive way to alleviate sarcopenia.
*Bifidobacterium animalis Probio-M8 improves sarcopenia physical performance by mitigating creatine restrictions imposed by microbial metabolites Full Text
Canadian Content Study
I was pleasantly surprised to see this study, as it marks the first time that I have seen work coming from Canada on extracellular vesicles(EVs). The researchers, led by Charles Ramassamy and first author Rummenigge Oliveira Silva from the Armand-Frappier Santé Biotechnologie Research Centre, used EVs from human plasma and fat cells to cross the blood brain barrier to deliver donepezil, a drug used in Alzheimer’s which is also anti-inflammatory, to zebrafish larvae. This resulted in not only reduced inflammation but also increased movement when challenged with an inflammatory molecule. EVs show great potential for longevity, and I hope to see this work continued in Canada.
Exploring the potential of plasma and adipose mesenchymal stem cell-derived extracellular vesicles as novel platforms for neuroinflammation therapy Full Text CAN
Not a study, but a review of the accomplishments of the Canadian Consortium on Neurodegeneration in Aging (CCNA), which has been running since 2014 and involves teams across Canada co-ordinating together to tackle dementia. This has resulted in the creation of a national dementia program, CAN-THUMBS UP. “CCNA is evidence that an organized “centrally-organized” approach to dementia research can catalyze important progress nationally and yield significant and measurable results.”
We need to set up something similar devoted to longevity and aging in general - the CLA will make that happen!
Further Canadian content is indicated by CAN
Supplemental Section
Lifestyle
*Tissue-specific methylomic responses to a lifestyle intervention in older adults associate with metabolic and physiological health improvements Full Text
*Associations of accelerometer-measured physical activity, sedentary behaviour, and sleep with next-day cognitive performance in older adults: a micro-longitudinal study Full Text***
*Effectiveness and feasibility of a theory-informed intervention to improve Mediterranean diet adherence, physical activity and cognition in older adults at risk of dementia: the MedEx-UK randomised controlled trial Full Text
Fasting/Dietary Restriction
*Effect of Three Different Daily Protein Intakes in a Two-Meal Eating Pattern on Protein Turnover in Middle Age and Older Adults: A Randomized Controlled Trial
*Multi-omic analysis of biological aging biomarkers in long-term calorie restriction and endurance exercise practitioners: A cross-sectional study Full Text
*The effect of Ramadan intermittent fasting on anthropometric, hormonal, metabolic, inflammatory, and oxidative stress markers in pre-and post-menopausal women: a prospective cohort of Saudi women Full Text
Diet
*Cardiovascular Protection Tracks With Wine Intake, Now Provable With Urinary Marker Full Text***
*A well-balanced vegan diet does not compromise daily mixed muscle protein synthesis rates when compared to an omnivorous diet in active older adults: a randomized controlled cross-over trial Full Text***
*Slower Pace of Epigenetic Aging and Lower Inflammatory Indicators in Females Following a Nutrient-Dense, Plant-Rich Diet Than Those in Females Following the Standard American Diet Full Text
Exercise
*The effects of high-intensity interval training on cognitive performance: a systematic review and meta-analysis Full Text***
*Exercise training alters resting brain-derived neurotrophic factor concentration in older adults: A systematic review with meta-analysis of randomized-controlled trials Full Text
*Long-term impact of adherence to muscle-strengthening guidelines on inflammation markers: a 17-year follow-up study with obesity parameters as mediators Full Text
Non-prescription Supplements (in alphabetical order)
Astaxanthin
Delivery systems for astaxanthin: A review on approaches for in situ dosage in the treatment of inflammation associated diseases Full Text
Biological activities of astaxanthin in the treatment of neurodegenerative diseases
Oral administration of astaxanthin mitigates chronological skin aging in mice
Curcumin
*Evaluation of curcumin intake in reducing exercise-induced muscle damage in athletes: a systematic review Full Text***
Efficacy and mechanisms of curcumin in the treatment of osteoarthritis: A scoping review Full Text
The Dynamic Role of Curcumin in Mitigating Human Illnesses: Recent Advances in Therapeutic Applications Full Text
Fisetin
Fisetin as a Blueprint for Senotherapeutic Agents — Elucidating Geroprotective and Senolytic Properties with Molecular Modeling Full Text
Melatonin
*12-week melatonin intake attenuates cardiac autonomic dysfunction and oxidative stress in multiple sclerosis patients: a randomized controlled trial
The potential therapeutic role of melatonin in organ fibrosis: a comprehensive review Full Text
Protective Effects of Exogenous Melatonin Administration on White Fat Metabolism Disruption Induced by Aging and a High-Fat Diet in Mice Full Text
Nicotinamide MonoNucleotide (NMN)
Rejuvenating aged osteoprogenitors for bone repair Full Text
Resveratrol
Resveratrol alleviates heart failure by activating foxo3a to counteract oxidative stress and apoptosis Full Text
Resveratrol and Extra Virgin Olive Oil: Protective Agents Against Age-Related Disease Full Text
Spermidine
*The Association of Dietary Polyamines with Mortality and the Risk of Cardiovascular Disease: A Prospective Study in UK Biobank Full Text
Spermidine Enhances Mitochondrial Bioenergetics in Young and Aged Human-Induced Pluripotent Stem Cell-Derived Neurons Full Text
Spermidine alleviates thymopoiesis defects and aging of the peripheral T-cell population in mice after radiation exposure Full Text
Other available supplements or natural substances (in alphabetical order)
*Beta-Alanine for Improving Exercise Capacity, Muscle Strength, and Functional Performance of Older Adults: A Systematic Review
*The impact of creatine levels on musculoskeletal health in the elderly: a mendelian randomization analysis Full Text
*The power of creatine plus resistance training for healthy aging: enhancing physical vitality and cognitive function Full Text
*The Association Between Dietary Magnesium Intake and Frailty in Patients with Chronic Obstructive Pulmonary Disease: National Health and Nutrition Examination Survey Full Text
The Neuroprotective Effect of Rooibos Herbal Tea Against Alzheimer's Disease: A Review Full Text
*The effects of whey protein supplementation on indices of cardiometabolic health: A systematic review and meta-analysis of randomized controlled trials Full Text
Combinations
*Comparative Efficacy of Glucosamine-Based Combination Therapies in Alleviating Knee Osteoarthritis Pain: A Systematic Review and Network Meta-Analysis Full Text
Co-administration of coenzyme Q10 and curcumin mitigates cognitive deficits and exerts neuroprotective effects in aluminum chloride-induced Alzheimer's disease in aged mice Full Text
Prescription Supplements
Metformin
*Metformin Treatment With or Without Mediterranean Diet for the Prevention of Age-Related Diseases in People With Metabolic Syndrome: The MeMeMe Randomized Trial Full Text
A Systematic Review on Clinical Evidence for Topical Metformin: Old Medication With New Application Full Text
Metformin in Antiviral Therapy: Evidence and Perspectives Full Text
Rapamycin (sirolimus)
Rapamycin administration causes a decrease in muscle contractile function and systemic glucose intolerance concomitant with reduced skeletal muscle Rictor, the mTORC2 component, expression independent of energy intake in young rats Full Text
Miscellaneous Molecules & Prescription Drugs
*Anti-diabetic agents and the risks of dementia in patients with type 2 diabetes: a systematic review and network meta-analysis of observational studies and randomized controlled trials Full Text***
Losartan attenuates sex-dependent hypertension, neuroinflammation, and cognitive impairment in the aging male sprague–dawley rat Full Text
Spotlight on the Mechanism of Action of Semaglutide Full Text
Novel Molecules
Intestinal mucosal barrier repair and immune regulation with an AI-developed gut-restricted PHD inhibitor Full Text*** CAN
The metabolically resistant apelin-17 analog LIT01-196 reduces cardiac dysfunction and remodeling in heart failure after myocardial infarction Full Text
*Safety, Tolerability and Pharmacokinetic-Pharmacodynamic Relationship of NX210c Peptide in Healthy Elderly Volunteers: Randomized, Placebo-Controlled, Double-Blind, Multiple Ascending Dose Study Full Text
Other Areas of Interest (in alphabetical order)
Ageing Clocks & other biomarkers of ageing
*Metabolomic age (MileAge) predicts health and life span: A comparison of multiple machine learning algorithms Full Text
Critical review of aging clocks and factors that may influence the pace of aging Full Text
The Immunosenescence Clock: A New Method for Evaluating Biological Age and Predicting Mortality Risk Full Text
Biomarkers
An expert consensus statement on biomarkers of ageing for use in intervention studies Full Text
*Phenotypic upregulation of hexocylceramides and ether-linked phosphocholines as markers of human extreme longevity Full Text
*Biomarkers of cellular senescence and major health outcomes in older adults Full Text
Blood Factors or other Heterochronic Transplantation
The dominance of old blood, and age-related increase in protein production and noise Full Text
*A phase 2 pilot study of umbilical cord blood infusion as an adjuvant consolidation therapy in elderly patients with acute myeloid leukemia Full Text***
Exosomes (small packets of information released by cells)
*Plasma extracellular vesicles carry immune system-related peptides that predict human longevity Full Text
Comparative Analysis of the Therapeutic Potential of Extracellular Vesicles Secreted by Aged and Young Bone Marrow-Derived Mesenchymal Stem Cells in Osteoarthritis Pathogenesis Full Text
Mesenchymal Stem Cell-Derived Exosomes: A Promising Therapeutic Strategy for Age-Related Diseases Full Text***
Genetics including CRISPR
A Potential Gene Therapy for Hearing Loss Full Text***
Cardiac bridging integrator 1 gene therapy rescues chronic non-ischemic heart failure in minipigs Full Text
*Lack of association between common polymorphisms associated with successful aging and longevity in the population of Sardinian Blue Zone Full Text
Lifespan Lengthening Interventions
Lithocholic acid phenocopies anti-ageing effects of calorie restriction Full Text
Lifelong Glutathione Deficiency in Mice Increased Lifespan and Delayed Age-Related Motor Declines Full Text
Hesperetin Increases Lifespan and Antioxidant Ability Correlating with IIS, HSP, mtUPR, and JNK Pathways of Chronic Oxidative Stress in Caenorhabditis elegans Full Text
Microbiome
*Diet-gut microbiome interaction and its impact on host blood glucose homeostasis: a series of nutritional n-of-1 trials Full Text
*Impact of daily avocado consumption on gut microbiota in adults with abdominal obesity: an ancillary study of HAT, a randomized controlled trial Full Text
Gut microbiota metabolism of branched-chain amino acids and their metabolites can improve the physiological function of aging mice Full Text
Observational Studies
*Dementia Incidence in Quebec Over 20 Years Full Text CAN
*New Disability in a Cohort Study of Older Men—The Manitoba Follow-Up Study Full Text CAN
*Adverse changes in close social ties in aging women and men: A population-based longitudinal study of the CLSA (2011–2021) Full Text CAN
*Impact of Age on Rheumatic Immune-related Adverse Events: Experience from the Canadian Research Group of Rheumatology in Immuno-Oncology (CanRIO) CAN
*A standard procedure for constructing a multi-level social vulnerability index using CLSA and SOS data as working examples Full Text CAN
*Association of urban green and blue space with accelerated ageing: A cohort Study in the UK Biobank Full Text
*Cohort trends in intrinsic capacity in England and China Full Text
Opinion/Editorials/Theory/Policy
Canadian Clinical Guidelines on Social Isolation and Loneliness in Older Adults Full Text CAN
*Determinants of First Practice Location among Canadian Geriatric Medicine Trainees and Recent Graduates: Findings of a Cross-sectional Survey in 2023 Full Text CAN
Validation requirements for AI-based intervention-evaluation in aging and longevity research and practice Full Text
Disagreement on foundational principles of biological aging Full Text
On the causal connection in lifespan correlations and the possible existence of a ‘number of life’ at molecular level Full Text
Other Ageing Biology
Predicting the pro-longevity or anti-longevity effect of model organism genes with enhanced Gaussian noise augmentation-based contrastive learning on protein–protein interaction networks Full Text
Effects of Aging on Glucose and Lipid Metabolism in Mice Full Text
RANKL treatment restores thymic function and improves T cell–mediated immune responses in aged mice***
Reproductive Health
Berberine promotes primordial follicle activation and increases ovulated oocyte quantity in aged mice Full Text***
Dietary supplementation with lycopene improves semen quality and antioxidant status in breeder roosters Full Text
Canagliflozin treatment prevents follicular exhaustion and attenuates hallmarks of ovarian aging in genetically heterogenous mice
Reviews
Chaperone-mediated autophagy as a modulator of aging and longevity Full Text
Epigenetic modifications and emerging therapeutic targets in cardiovascular aging and diseases Full Text
Centenarians—the way to healthy vascular ageing and longevity: a review Full Text
Senolytics/Senescent Cells
Topical ABT-263 treatment reduces aged skin senescence and improves subsequent wound healing Full Text***
Precision Targeting of Senescent Cells Full Text
Senolysis by GLS1 Inhibition Ameliorates Kidney Aging by Inducing Excessive mPTP Opening through MFN1 Full Text
Generation of a selective senolytic platform using a micelle-encapsulated Sudan Black B conjugated analog Full Text
Skin & Beauty
*Efficacy and Safety of Topical Application of Plant-Based Products on Skin Aging in Healthy Individuals: A Systematic Review and Meta-Analysis of Randomized Controlled Trials Full Text
*Effects of Retinol, Natural Pea Peptide and Antioxidant Blend in a Topical Formulation: In Vitro and Clinical Evidence Full Text
*Phytoestrogens as Natural Anti-Aging Solutions for Enhanced Collagen Synthesis in Skin Full Text
*Silybum marianum Extract: A Highly Effective Natural Alternative to Retinoids to Prevent Skin Aging Without Side Effects Full Text
Stem Cells
*Safety and efficacy of autologous adipose-derived stem cells for knee osteoarthritis in the elderly population: A systematic review Full Text***
iPSC-derived mesenchymal stromal cells stimulate neovascularization less than their primary counterparts Full Text
Telomeres
Oral intake of degalactosylated whey protein increases peripheral blood telomere length in young and aged mice Full Text
*DNA methylation-based telomere length is more strongly associated with cardiovascular disease and long-term mortality than quantitative polymerase chain reaction-based telomere length: evidence from the NHANES 1999–2002 Full Text
The relationship between mitochondrial health, telomerase activity and longitudinal telomere attrition, considering the role of chronic stress Full Text
Odds & Sods
Hydra has mammal-like mutation rates facilitating fast adaptation despite its nonaging phenotype Full Text
Hallmarks of aging: A user’s guide for comparative biologists Full Text
Extreme longevity may be the rule not the exception in Balaenid whales 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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