Epigenetic regulation of aging: implications for interventions of aging and diseases

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Ноя. 7, 2022

Abstract Aging is accompanied by the decline of organismal functions and a series prominent hallmarks, including genetic epigenetic alterations. These aging-associated changes include DNA methylation, histone modification, chromatin remodeling, non-coding RNA (ncRNA) regulation, all which participate in regulation aging process, hence contribute to aging-related diseases. Therefore, understanding mechanisms will provide new avenues develop strategies delay aging. Indeed, interventions based on manipulating have led alleviation or extension lifespan animal models. Small molecule-based therapies reprogramming that enable rejuvenation been developed for ameliorating reversing conditions. In addition, adopting health-promoting activities, such as caloric restriction, exercise, calibrating circadian rhythm, has demonstrated Furthermore, various clinical trials intervention are ongoing, providing more evidence safety efficacy these therapies. Here, we review recent work outline advances age-associated A better critical roles epigenetics process lead prevention human therapy

Язык: Английский

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Stress, epigenetics, and aging: Unraveling the intricate crosstalk

Molecular Cell, Год журнала: 2023, Номер 84(1), С. 34 - 54

Опубликована: Ноя. 13, 2023

Язык: Английский

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A single-cell transcriptomic atlas of exercise-induced anti-inflammatory and geroprotective effects across the body

The Innovation, Год журнала: 2023, Номер 4(1), С. 100380 - 100380

Опубликована: Янв. 1, 2023

•An atlas of age-, tissue-, and cell-type-specific benefits long-term exercise.•Exercise protects tissues from infectious injury, especially in younger ones.•Exercise promotes rejuvenation aged tissues, the nervous system.•Exercise exerts geroprotective effects, by resetting circadian programs via clock protein BMAL1. Exercise whole organism, yet, how across body orchestrally respond to exercise remains enigmatic. Here, young old mice, with or without exercise, exposed we characterized phenotypic molecular adaptations a 12-month 14 tissues/organs at single-cell resolution. Overall, although more effectively animals, individuals terms inflammaging suppression tissue rejuvenation, structural improvement central system systemic vasculature being most prominent. In vascular endothelial cells, found that readjusting rhythmic machinery core BMAL1 delayed senescence facilitated recovery damage, recapitulating beneficial effects exercise. Our study underscores effect reconstituting youthful network provides foundation for further investigating interplay between aging, immune challenges organism.

Язык: Английский

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Emerging epigenetic insights into aging mechanisms and interventions

Trends in Pharmacological Sciences, Год журнала: 2024, Номер 45(2), С. 157 - 172

Опубликована: Янв. 11, 2024

Язык: Английский

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An Evidence-Based Narrative Review of Mechanisms of Resistance Exercise–Induced Human Skeletal Muscle Hypertrophy

Medicine & Science in Sports & Exercise, Год журнала: 2022, Номер 54(9), С. 1546 - 1559

Опубликована: Апрель 6, 2022

Skeletal muscle plays a critical role in physical function and metabolic health. Muscle is highly adaptable tissue that responds to resistance exercise (RE; loading) by hypertrophying, or during disuse, RE mitigates loss. Resistance training (RET)-induced skeletal hypertrophy product of external (e.g., programming, diet, some supplements) internal variables mechanotransduction, ribosomes, gene expression, satellite cells activity). undeniably the most potent nonpharmacological variable stimulate activation/suppression linked muscular countering disuse-induced Here, we posit despite considerable research on impact RET hypertrophy, (i.e., inherent biology) are dominant regulating extent response stimuli. Thus, identifying key muscle-derived mediate translation will be pivotal determining effective strategies for healthy persons. Such work aid enhancing clinical populations, slowing functional decline, promoting mobility. We provide up-to-date, evidence-based perspectives mechanisms RET-induced hypertrophy.

Язык: Английский

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Late‐life exercise mitigates skeletal muscle epigenetic aging

Aging Cell, Год журнала: 2021, Номер 21(1)

Опубликована: Дек. 21, 2021

Abstract There are functional benefits to exercise in muscle, even when performed late life, but the contributions of epigenetic factors late‐life adaptation poorly defined. Using reduced representation bisulfite sequencing (RRBS), ribosomal DNA (rDNA) and mitochondrial‐specific examination methylation, targeted high‐resolution methylation analysis, DNAge™ aging clock analysis with a translatable model voluntary murine endurance/resistance training (progressive weighted wheel running, PoWeR), we provide evidence that may mitigate skeletal muscle. Late‐life PoWeR from 22–24 months age modestly significantly attenuates an age‐associated shift toward promoter hypermethylation. The muscle old mice PoWeR‐trained for eight weeks was approximately younger than 24‐month‐old sedentary counterparts, which represents ~8% expected lifespan. These data molecular basis as therapy attenuate aging.

Язык: Английский

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Human age reversal: Fact or fiction?

Aging Cell, Год журнала: 2022, Номер 21(8)

Опубликована: Июль 2, 2022

Although chronological age correlates with various age-related diseases and conditions, it does not adequately reflect an individual's functional capacity, well-being, or mortality risk. In contrast, biological provides information about overall health indicates how rapidly slowly a person is aging. Estimates of are thought to be provided by aging clocks, which computational models (e.g., elastic net) that use set inputs DNA methylation sites) make prediction. the past decade, clock studies have shown several diseases, social variables, mental conditions associate increase in predicted relative age. This phenomenon acceleration linked higher risk premature mortality. More recent research has demonstrated sensitive specific interventions. Human trials reported caloric restriction, plant-based diet, lifestyle changes involving exercise, drug regime including metformin, vitamin D3 supplementation all capable slowing down reversing clock. Non-interventional connected high-quality sleep, physical activity, healthy other factors deceleration. Specific molecules been associated reduction reversal age, such as antihypertensive doxazosin metabolite alpha-ketoglutarate. rigorous clinical needed validate these initial findings, existing data suggest clocks malleable humans. Additional warranted better understand significance lowering their outputs.

Язык: Английский

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Exercise is associated with younger methylome and transcriptome profiles in human skeletal muscle

Aging Cell, Год журнала: 2023, Номер 23(1)

Опубликована: Май 2, 2023

Exercise training prevents age-related decline in muscle function. Targeting epigenetic aging is a promising actionable mechanism and late-life exercise mitigates rodent muscle. Whether can decelerate, or reverse humans unknown. Here, we performed powerful meta-analysis of the methylome transcriptome an unprecedented number human skeletal samples (n = 3176). We show that: (1) individuals with higher baseline aerobic fitness have younger transcriptomic profiles, (2) leads to significant shifts patterns toward profile, (3) disuse "ages" transcriptome. Higher levels were associated attenuated differential methylation transcription during aging. Furthermore, both profiles shifted state after interventions, while older forced disuse. demonstrate that targets many transcripts DNA loci maintain specifically genes related structure, metabolism, mitochondrial Our comprehensive analysis will inform future studies aiming identify best combination therapeutics regimes optimize longevity.

Язык: Английский

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Skeletal muscle memory

AJP Cell Physiology, Год журнала: 2023, Номер 324(6), С. C1274 - C1294

Опубликована: Май 8, 2023

Skeletal muscle memory is an exciting phenomenon gaining significant traction across several scientific communities, among exercise practitioners, and the public. Research has demonstrated that skeletal tissue can be “primed” by earlier positive encounters with training enhance adaptation to later retraining, even following periods of cessation or detraining. This review will describe discuss most recent research investigating underlying mechanisms memory: 1) “cellular” and, 2) “epigenetic” memory, as well emerging evidence how these theories may work in synergy. We both “positive” “negative” highlight importance for optimizing interventions programs development therapeutic strategies counteracting wasting conditions age-related loss. Finally, important directions field highlighted advance next generation studies into future.

Язык: Английский

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Advancing personalized medicine in neurodegenerative diseases: The role of epigenetics and pharmacoepigenomics in pharmacotherapy

Pharmacological Research, Год журнала: 2024, Номер 205, С. 107247 - 107247

Опубликована: Июнь 2, 2024

About 80% of brain disorders have a genetic basis. The pathogenesis most neurodegenerative diseases is associated with myriad defects, epigenetic alterations (DNA methylation, histone/chromatin remodeling, miRNA dysregulation), and environmental factors. emergence new sequencing technologies tools to study the epigenome has led identifying predictive biomarkers for earlier diagnosis, opening up possibility prophylactical interventions. As result, advances in pharmacogenetics pharmacoepigenomics now allow personalized treatments based on profile each patient specific mechanisms involved. This Review highlights complexity variability responses pharmacotherapy, emphasizing influence polymorphisms pharmacokinetics pharmacodynamics drugs used treat those conditions. We specifically discuss potential modulatory effect several an increased risk developing different diseases. explore genomic analyzing individual-specific drug metabolism predict response clinical outcomes. also provide insights into mechanism action under investigation their impact disease-modifying pathways. Finally, underscores great this field enhance effectiveness safety through medicine.

Язык: Английский

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