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

Aging Cell, Journal Year: 2023, Volume and Issue: 23(1)

Published: May 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.

Language: Английский

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Skeletal muscle memory

AJP Cell Physiology, Journal Year: 2023, Volume and Issue: 324(6), P. C1274 - C1294

Published: May 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.

Language: Английский

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A novel deep proteomic approach in human skeletal muscle unveils distinct molecular signatures affected by aging and resistance training

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

Published: April 19, 2024

Aging | doi:10.18632/aging.205751. Michael D. Roberts, Bradley A. Ruple, Joshua S. Godwin, Mason C. McIntosh, Shao-Yung Chen, Nicholas J. Kontos, Anthony Agyin-Birikorang, Max Michel, Daniel L. Plotkin, Madison Mattingly, Brooks Mobley, Tim N. Ziegenfuss, Andrew Fruge, Andreas Kavazis

Language: Английский

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Unraveling the link between cardiorespiratory fitness and cancer: a state-of-the-art review

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

Published: June 3, 2024

Abstract Cardiorespiratory fitness (CRF) not only reflects an individual’s capacity to perform physical activities but also encapsulates broader effects on the basic biology of aging. This review aims summarize evidence influence CRF overall and site-specific cancer risks. It delves into biological mechanisms through which may exert its effects, explores clinical implications these findings, identifies gaps in current base, suggests directions for future research. The synthesis findings reveals that higher levels (general threshold > 7 METs) are consistently associated with a reduced risk range cancers, including head neck, lung, breast, gastrointestinal, particularly pancreatic colorectal, bladder, incidence mortality, potentially stomach liver, bile duct, gall bladder cancers. These inverse associations between do generally differ across age groups, sex, race, or adiposity, suggesting universal protective effect CRF. Nonetheless, linking skin, mouth pharynx, kidney, endometrial cancers is limited inconclusive. Conversely, be linked increased prostate hematological malignancies, such as leukemia myeloma, although still conclusive. appears play significant role reducing several various mechanisms, inflammation reduction, immune system enhancement, hormonal regulation, metabolic improvements. Overall, enhancing regular activity offers vital, accessible strategy extending health span. Future research should aim fill existing regarding specific elucidate detailed dose–response relationships risk. Studies needed causal mechanistic pathways outcomes.

Language: Английский

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Sex differences in muscle protein expression and DNA methylation in response to exercise training

Biology of Sex Differences, Journal Year: 2023, Volume and Issue: 14(1)

Published: Sept. 5, 2023

Exercise training elicits changes in muscle physiology, epigenomics, transcriptomics, and proteomics, with males females exhibiting differing physiological responses to exercise training. However, the molecular mechanisms contributing adaptations between sexes are poorly understood.We performed a meta-analysis for sex differences skeletal DNA methylation following an endurance intervention (Gene SMART cohort E-MTAB-11282 cohort). We investigated proteome Lastly, we whether methylome associated baseline cardiorespiratory fitness (maximal oxygen consumption; VO2max) sex-specific manner.Here, first time, response human (n = 78; 50 males, 28 females). identified 92 sites (CpGs) training; however, no CpGs changed sex-dependent manner. In contrast, 189 proteins that differentially expressed training, 82 at baseline. Proteins showing most robust include SIRT3, MRPL41, MBP. Irrespective of sex, was (19,257 CpGs) proteomic changes. did not observe association methylome. Integrative multi-omic analysis mitochondrial metabolism pathways responses. shifted methylomes be more similar sexes.We protein expression changes, but intervention; whereas or lifelong Given delicate interaction as well limitations current study, studies required elucidate there is effect on found genes involved modulated These results shed light muscle.

Language: Английский

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An Integrated Neuromuscular Training Intervention Applied in Primary School Induces Epigenetic Modifications in Disease‐Related Genes: A Genome‐Wide DNA Methylation Study

Scandinavian Journal of Medicine and Science in Sports, Journal Year: 2025, Volume and Issue: 35(1)

Published: Jan. 1, 2025

Physical exercise has been shown to induce epigenetic modifications with various health implications, directly affect DNA methylation (DNAm), as well reverse the age. Hence, we aimed identify differential changes and assess age in saliva of 7-9-year-old school children following a 3-month integrated neuromuscular training (INT), explore if any are core genes. Core genes defined high relevance essential importance within human genome. Forty (17 boys 23 girls) were recruited from schools Girona, Spain, allocated into control (N = 20) or INT group. The group performed warm-up during physical education (PE) classes, encompassing strength, coordination, dynamic stabilization, plyometrics, speed, agility exercises, whereas traditional activities, aerobic exercises that will prepare cardiovascular system increase joint mobility for upcoming effort class. Genome-wide DNAm analysis was Illumina 900 K microarray. recognized based on accomplishment rigorous widely accepted 3-point criteria: participation enriched pathways, connectivity (≥ 10), target key transcription factors. There 1200 differentially methylated positions (DMPs) 414 DMPs (FDR < 0.05, p Aβ |0.1|), suggesting non-significant trend acceleration (1.18 months, > 0.05) 1-month decrease (p 0.05). showed low similarity between pathways interconnectivity, distinct mostly development growth-related. Additionally, no identified Interestingly, related involving signaling mechanisms, hormone protein metabolism pathways. Moreover, 17 main findings present study an response stimulus INT, including considered Trial Registration: protocol registered ISRCTN registry (ISRCTN16744821).

Language: Английский

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A primer on global molecular responses to exercise in skeletal muscle: Omics in focus

Journal of sport and health science/Journal of Sport and Health Science, Journal Year: 2025, Volume and Issue: unknown, P. 101029 - 101029

Published: Feb. 1, 2025

Advances in skeletal muscle omics has expanded our understanding of exercise-induced adaptations at the molecular level. Over past 2 decades, transcriptome studies have detailed acute and chronic responses to resistance, endurance, concurrent exercise, focusing on variables such as training status, nutrition, age, sex, metabolic health profile. Multi-omics approaches, integration transcriptomic epigenetic data, along with emerging ribosomal RNA sequencing advancements, further provided insights into how adapts exercise across lifespan. Downstream transcriptome, proteomic phosphoproteomic identified novel regulators adaptations, while single-cell/nucleus spatial technologies promise evolve cellular specialization communication around cells. This narrative review highlights (a) historical foundations muscle, (b) current research 3 layers cascade (DNA, RNA, protein), (c) applications single-cell study adaptation exercise. Further elaboration muscle's global footprint using multi-omics methods will help researchers practitioners develop more effective targeted approaches improve well athletic performance.

Language: Английский

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Dnmt3a overexpression disrupts skeletal muscle homeostasis, promotes an aging-like phenotype, and reduces metabolic elasticity

iScience, Journal Year: 2025, Volume and Issue: 28(4), P. 112144 - 112144

Published: March 4, 2025

Mammalian aging is reportedly driven by the loss of epigenetic information; however, its impact on skeletal muscle remains unclear. This study shows that mouse exhibits increased DNA methylation, and overexpression methyltransferase 3a (Dnmt3a) induces an aging-like phenotype. Muscle-specific Dnmt3a leads to increase in central nucleus-positive myofibers, predominantly fast-twitch fibers, a shift toward slow-twitch elevated inflammatory senescence markers, mitochondrial OXPHOS complex I reduction, decreased basal autophagy. resulted reduced mass strength impaired endurance exercise capacity with age, accompanied enhanced signature. In addition, not only sensitivity starvation-induced atrophy but also restorability from atrophy. These findings suggest methylation disrupts homeostasis, promotes phenotype, reduces metabolic elasticity.

Language: Английский

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Serum Proteomic and Metabolomic Signatures of High Versus Low Physical Function in Octogenarians

Aging Cell, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Physical function declines with aging, yet there is considerable heterogeneity, some individuals declining very slowly while others experience accelerated functional decline. To gain insight into mechanisms promoting high physical we performed proteomics, targeted metabolomics, and kynurenine-focused metabolomic analyses on serum specimens from three groups of octogenarians: High-functioning master athletes (HF, n = 16), healthy normal-functioning non-athletes (NF, 12), lower functioning (LF, 11). Higher performance status was associated evidence consistent with: Lower levels circulating proinflammatory markers, as well unperturbed tryptophan metabolism, the normal kynurenic pathway; higher lysophosphatidylcholines that have been previously better mitochondrial oxidative capacity; activity integrated stress response; SASP protein members; proteins reflect neurodegeneration/denervation. Extending observations previous studies focused biomarkers aging predict poor function, our findings show many same exhibit attenuated changes in those who maintain a function. Because cross-sectional nature this study, results should be interpreted caution, bidirectional causality, where behavior both cause outcome differences biomarker changes, remains possible interpretation.

Language: Английский

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Associations Between Leisure‐Time Physical Activity and Metabolomics‐Based Markers of Biological Aging in Late Midlife: Short‐Term and Long‐Term Follow‐Up

Aging Cell, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

ABSTRACT Physical activity (PA) may delay the onset of age‐related diseases by decelerating biological aging. We investigated association between leisure‐time physical (LTPA) and metabolomics‐based aging markers (MetaboAge MetaboHealth) in late midlife during 16 years follow‐up. At 16‐year follow‐up, we also device‐based PA MetaboAge MetaboHealth. included 1816 individuals (mean age 61.6 years) from Helsinki Birth Cohort Study at baseline followed them up for 5 ( n = 982) 744), respectively. LTPA was assessed via questionnaire later with ActiGraph accelerometer Fasting blood samples were applied to calculate acceleration (ΔmetaboAge) MetaboHealth both follow‐ups. Covariate‐adjusted multiple regression analyses linear mixed models study associations. A higher volume associated a lower score 5‐year follow‐up p < 0.0001 time × interaction). No associations detected An increase over decrease 0.001) an score. Higher score, but not ΔmetaboAge. In conclusion, old improved Increasing protect against MetaboHealth‐based The results support importance life.

Language: Английский

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