Harnessing Genetics to Extend Lifespan and Healthspan: Current Progress and Future Directions DOI Open Access
Paa Kwesi Ankrah,

Enock D Mensah,

Kwabena Dabie

et al.

Cureus, Journal Year: 2024, Volume and Issue: unknown

Published: March 4, 2024

Aging is inevitable, but the lifespan (duration of life) and healthspan (healthy aging) vary greatly among individuals across species. Unlocking secrets behind these differences has captivated scientific curiosity for ages. This review presents relevant recent advances in genetics cell biology that are shedding new light by untangling how subtle changes conserved genes, pathways, epigenetic factors influence organismal senescence associated declines. Biogerontology a complex rapidly growing field aimed at elucidating genetic modifications extend healthspan. explores gerontogenes, genes influencing Though exist, long-lived such as centenarians demonstrate extended healthspans, numerous studies confirm heritability longevity/healthspan genes. Importantly, gerontogenes directly indirectly involved DNA repair, insulin/IGF-1 mTOR signaling long non-coding RNAs, sirtuins, heat shock proteins. The interactions between epigenetics teased apart. While more research into optimizing needed, offer synergistic potential to forestall aging age-related diseases. Understanding longevity brings closer goal extending not only quality years life. primary aim human enhance healthspan, question remains: current effectively promoting healthy aging? article collates advancements improve alongside their challenges.

Language: Английский

Molecular mechanisms of aging and anti-aging strategies DOI Creative Commons
Yumeng Li,

Xutong Tian,

Juyue Luo

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: May 24, 2024

Abstract Aging is a complex and multifaceted process involving variety of interrelated molecular mechanisms cellular systems. Phenotypically, the biological aging accompanied by gradual loss function systemic deterioration multiple tissues, resulting in susceptibility to aging-related diseases. Emerging evidence suggests that closely associated with telomere attrition, DNA damage, mitochondrial dysfunction, nicotinamide adenine dinucleotide levels, impaired macro-autophagy, stem cell exhaustion, inflammation, protein balance, deregulated nutrient sensing, altered intercellular communication, dysbiosis. These age-related changes may be alleviated intervention strategies, such as calorie restriction, improved sleep quality, enhanced physical activity, targeted longevity genes. In this review, we summarise key historical progress exploration important causes anti-aging strategies recent decades, which provides basis for further understanding reversibility phenotypes, application prospect synthetic biotechnology therapy also prospected.

Language: Английский

Citations

61
Role of diet and exercise in aging, Alzheimer’s disease, and other chronic diseases DOI Creative Commons
Sachi Khemka,

Aananya Reddy,

Ricardo Isaiah Garcia

et al.

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 91, P. 102091 - 102091

Published: Oct. 12, 2023

Language: Английский

Citations

40
Body Size, Diet Quality, and Epigenetic Aging: Cross-Sectional and Longitudinal Analyses DOI Creative Commons

Danmeng Lily Li,

Allison Hodge, Lachlan Cribb

et al.

The Journals of Gerontology Series A, Journal Year: 2024, Volume and Issue: 79(4)

Published: Jan. 24, 2024

Epigenetic age is an emerging marker of health that highly predictive disease and mortality risk. There a lack evidence on whether lifestyle changes are associated with in epigenetic aging. We used data from 1 041 participants the Melbourne Collaborative Cohort Study blood DNA methylation measures at baseline (1990-1994, mean age: 57.4 years) follow-up (2003-2007, 68.8 years). The Alternative Healthy Eating Index-2010 (AHEI-2010), Mediterranean Dietary Score, Inflammatory Index were as diet quality, weight, waist circumference, waist-to-hip ratio body size. Five age-adjusted aging considered: GrimAge, PhenoAge, PCGrimAge, PCPhenoAge, DunedinPACE. Multivariable linear regression models including restricted cubic splines to assess cross-sectional longitudinal associations size quality Associations between weight cross-sectionally both time points positive appeared greater for DunedinPACE (per SD: β ~0.24) than GrimAge PhenoAge (β ~0.10). change markedly nonlinear (U-shaped) stable being lowest follow-up, except DunedinPACE, which only gain showed association. found negative, AHEI-2010 longitudinally. Other adiposity dietary scores similar results. In middle-aged older adults, declining may increase age, while association loss require further investigation. Our study sheds light potential management improvement slowing processes.

Language: Английский

Citations

10
To promote healthy aging, focus on the environment DOI
Daniel W. Belsky, Andrea Baccarelli

Nature Aging, Journal Year: 2023, Volume and Issue: 3(11), P. 1334 - 1344

Published: Nov. 9, 2023

Language: Английский

Citations

22
New horizons in life extension, healthspan extension and exceptional longevity DOI Creative Commons
David G. Le Couteur, Nir Barzilai

Age and Ageing, Journal Year: 2022, Volume and Issue: 51(8)

Published: Aug. 2, 2022

Abstract Many common chronic diseases and syndromes are ageing-related. This raises the prospect that therapeutic agents target biological changes of ageing will prevent or delay multiple with a single therapy. Gerotherapeutic drugs those pathways involved in ageing, aims reducing burden ageing-related increasing lifespan healthspan. The approach to discovering gerotherapeutic is similar used discover for diseases. includes screening novel compounds act on receptors influence repurposing currently available other indications. A involves studying populations exceptional longevity, order identify genes variants linked longer could be targeted by drugs. Metformin, rapamycin precursors nicotinamide adenine dinucleotide amongst frontrunners gerotherapeutics moving into human clinical trials evaluate their effects ageing. There also numbers potential pipeline being studied animal models. key hurdle designing both feasible can provide sufficient evidence support licencing marketing

Language: Английский

Citations

28
Educational Mobility, Pace of Aging, and Lifespan Among Participants in the Framingham Heart Study DOI Creative Commons
Gloria Huei-Jong Graf, Allison E. Aiello, Avshalom Caspi

et al.

JAMA Network Open, Journal Year: 2024, Volume and Issue: 7(3), P. e240655 - e240655

Published: March 1, 2024

Importance People who complete more education live longer lives with better health. New evidence suggests that these benefits operate through a slowed pace of biological aging. If so, measurements the aging could offer intermediate end points for studies how interventions to promote will affect healthy longevity. Objective To test hypothesis upward educational mobility is associated slower and increased Design, Setting, Participants This prospective cohort study analyzed data from 3 generations participants in Framingham Heart Study: (1) original cohort, enrolled beginning 1948; (2) Offspring 1971; (3) Gen3 2002. A 3-generation database was constructed quantify intergenerational mobility. Mobility were linked blood DNA-methylation collected 2005 2008 (n = 1652) 2009 2011 1449). Follow-up ongoing. Data analysis conducted June 2022 November 2023 using obtained National Institutes Health Genotypes Phenotypes (dbGaP). Exposure Educational measured by comparing participants’ outcomes those their parents. Main Outcomes Measures The whole-blood DunedinPACE epigenetic clock. For comparison purposes, repeated 4 other clocks. Survival follow-up 2019. Results 3101 Study; 1652 (mean [SD] age, 65.57 [9.22] years; 764 [46.2%] male) 1449 45.38 [7.83] 691 [47.7%] male). upwardly mobile terms tended have later life ( r −0.18 [95% CI, −0.23 −0.13]; P < .001). pattern association similar across held within-family sibling comparisons. There 402 died over period. Upward lower mortality risk (hazard ratio, 0.89 0.81 0.98]; .01). Slower accounted approximately half this association. Conclusions Relevance study’s findings support attainment may slow Epigenetic clocks potential as near-term outcome measures intervention effects on Experimental needed confirm findings.

Language: Английский

Citations

6
The Relationship between Dietary Macronutrient Composition and Telomere Length Among US Adults DOI Creative Commons
Nicholas A. Koemel, Nasser Laouali, Alistair M. Senior

et al.

Advanced Biology, Journal Year: 2024, Volume and Issue: 8(4)

Published: Jan. 16, 2024

Abstract The role of dietary macronutrients and energy intake in the aging process has been well‐established. However, previous research mainly focused on association between leukocyte telomere length (LTL) individual macronutrients, while effects macronutrient composition LTL remain unclear. This cross‐sectional analysis involved 4130 US adults (44.8 ± 17.0 years; 51% female) from National Health Nutrition Examination Survey during 1999–2002. A single 24‐h recall is used to collect data. relationship examined using three‐dimensional generalized additive models. After adjustment for age, sex, ethnicity, education, physical activity, BMI, quality, a with (P = 0.02) revealed. Diets lower protein (5–10%), higher carbohydrates (75%), fat (15–20%) are associated longest corresponding 7.7 years slower biological aging. lowest (5%) carbohydrate (40%), highest (55%) shortest LTL, accelerated 4.4 years. associations appeared magnified intake. These findings support complex independent diet quality.

Language: Английский

Citations

4
Regulation and mechanism of Bletilla striata polysaccharide on delaying aging in Drosophila melanogaster DOI

Eqra Hafeez,

Dongsheng Du,

Hang Ni

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 143382 - 143382

Published: April 1, 2025

Language: Английский

Citations

0
Short-term periodic restricted feeding elicits metabolome-microbiome signatures with sex dimorphic persistence in primate intervention DOI Creative Commons
Hagai Yanai, Bongsoo Park, Hyunwook Koh

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 5, 2024

Abstract Dietary restriction has shown benefits in physiological, metabolic, and molecular signatures associated with aging but is a difficult lifestyle to maintain for most individuals. In mice, less restrictive diet that allows cyclical periods of reduced calories mitigates phenotypes, yet the effects such an intervention genetically heterogenous, higher-order mammal not been examined. Here, using middle-aged rhesus macaques matched age sex, we show regimen 4 days low-calorie intake followed by 10 ad libitum feeding (4:10 diet) performed repeating cycles over 12 weeks led significant loss weight fat percentage, despite free access food study duration. We 4-day period sufficient drive alterations serum metabolome characterized substantial differences lipid classes. These phenotypes were paralleled changes gut microbiome restricted monkeys highlight involvement microbiome-metabolome axis. This shows promising some sex-dimorphic responses, including residual memory diet. As many calorie interventions are sustain, propose this short-term may be easier adhere have directly relevant human aging.

Language: Английский

Citations

3
The Role of Genetic Variation in Shaping Phenotypic Responses to Diet in AgingDrosophila melanogaster DOI Creative Commons
Nikolaj Bak, Trudy F. C. Mackay, Fabio Morgante

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Nutrition plays a central role in healthy living, however, extensive variability individual responses to dietary interventions complicates our understanding of its effects. Here we present comprehensive study utilizing the Drosophila Genetic Reference Panel (DGRP), investigating how genetic variation influences diet and aging. Quantitative analyses impact restriction on lifespan, locomotor activity, dry weight, heat knockdown time were performed. Locomotor weight measured same flies. We found significant genotype-by-diet interaction (GDI) genotype-by-age (GAI) for all traits. Therefore, environmental factors play crucial shaping trait at different ages diets, and/or distinct these traits diets. Our genome wide association also identified quantitative locus age-dependent response. The observed GDI GAI indicates that susceptibility changes as organisms age, which could have implications recommendations aimed promoting aging humans. identification associations between DNA sequence opens new avenues research into mechanisms underlying interactions.

Language: Английский

Citations

0