Molecular and Structural Alterations of Skeletal Muscle Tissue Nuclei during Aging

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1833 - 1833

Published: Feb. 2, 2024

Aging is accompanied by a progressive loss of skeletal muscle mass and strength. The mechanisms underlying this phenomenon are certainly multifactorial still remain to be fully elucidated. Changes in the cell nucleus structure function have been considered among possible contributing causes. This review offers an overview current knowledge on nuclei aging, focusing impairment nuclear pathways potentially involved age-related decline. In two types cells present: fiber cells, constituting contractile containing hundreds myonuclei, satellite i.e., myogenic mononuclear stem occurring at periphery fibers responsible for growth repair. Research conducted different experimental models with methodological approaches demonstrated that both myonuclei aged muscles undergo several structural molecular alterations, affecting chromatin organization, gene expression, transcriptional post-transcriptional activities. These alterations play key role homeostasis regeneration, thus decrease function.

Language: Английский

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Muscle-Specific Cellular and Molecular Adaptations to Late-Life Voluntary Concurrent Exercise

Function, Journal Year: 2022, Volume and Issue: 3(4)

Published: Jan. 1, 2022

Murine exercise models can provide information on factors that influence muscle adaptability with aging, but few translatable solutions exist. Progressive weighted wheel running (PoWeR) is a simple, voluntary, low-cost, high-volume endurance/resistance approach for training young mice. In the current investigation, aged mice (22-mo-old) underwent modified version of PoWeR 8 wk. Muscle functional, cellular, biochemical, transcriptional, and myonuclear DNA methylation analyses an encompassing picture how from responds to combined training. Mice run 6-8 km/d, relative sedentary mice, increases plantarflexor strength. The oxidative soleus similarly in every parameter measured previous work; this includes mass, glycolytic-to-oxidative fiber type transitioning, size, satellite cell frequency, number. oxidative/glycolytic plantaris adapts according type, modest overall changes mass. Capillarity markedly both muscles, which may be permissive advanced age. Comparison published RNA-sequencing data identified conserved regulators across age muscles; Aldh1l1 associates vasculature. Agrn Samd1 gene expression upregulated after simultaneous hypomethylated promoter CpG DNA, could have implications innervation capillarization. A Rbm10 by late-life myonuclei, consistent findings tissue. herein are resource uncovering cellular molecular adaptation aging.

Language: Английский

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A molecular signature defining exercise adaptation with ageing and in vivo partial reprogramming in skeletal muscle

The Journal of Physiology, Journal Year: 2022, Volume and Issue: 601(4), P. 763 - 782

Published: Dec. 19, 2022

Abstract Exercise promotes functional improvements in aged tissues, but the extent to which it simulates partial molecular reprogramming is unknown. Using transcriptome profiling from (1) a skeletal muscle‐specific vivo Oct3/4 , Klf4 Sox2 and Myc (OKSM) reprogramming‐factor expression murine model; (2) an inducible induction (3) translatable high‐volume hypertrophic exercise training approach mice; (4) human muscle biopsies, we collectively defined exercise‐induced genes that are common reprogramming. Late‐life lowered DNA methylation age according several contemporary clocks. A comparison of soleus after late‐life OKSM revealed overlapping signature included higher JunB Sun1 . Also, within this signature, downregulation specific mitochondrial muscle‐enriched was conserved long‐term exercise‐trained humans; among these Abra/Stars factor most induced by elevated following mice. pulse MYC rewired global methylome, partially recapitulated induction. also emerged MYC‐controlled adaptation transcriptomes, including lower Melusin reactive oxygen species‐associated Romo1 With mice, as well habitual humans, complex I accessory subunit Ndufb11 lower; low linked longevity rodents. Collectively, shares similarities with genetic image Key points Advances last decade related cellular epigenetic (e.g. methylome remodelling) toward pluripotent state via Yamanaka transcription factors provide window into potential mechanisms for combatting deleterious effects ageing. gene analysis, compared OKSM‐mediated fibres mice muscle. muscle, so factor‐mediated mRNA landscapes humans. single sufficient remodel methylome. We identify reprogramming‐associated innately altered propose contributes some responses.

Language: Английский

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Exercise couples mitochondrial function with skeletal muscle fiber type via ROS-mediated epigenetic modification

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 213, P. 409 - 425

Published: Jan. 29, 2024

Skeletal muscle is a heterogeneous tissue composed of different types fibers, demonstrating substantial plasticity. Physiological or pathological stimuli can induce transitions in fiber types. However, the precise regulatory mechanisms behind these remains unclear. This paper reviews classification and characteristics along with classical type transitions. Additionally, role exercise-induced disease intervention reviewed. Epigenetic pathways mediate cellular adaptations thus represent potential targets for regulating focuses on by which epigenetic modifications couple mitochondrial function contraction characteristics. Reactive Oxygen Species (ROS) are critical signaling regulators health-promoting effects exercise. Finally, we discuss ROS transition

Language: Английский

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Epigenetic control of skeletal muscle atrophy

Cellular & Molecular Biology Letters, Journal Year: 2024, Volume and Issue: 29(1)

Published: July 8, 2024

Abstract Skeletal muscular atrophy is a complex disease involving large number of gene expression regulatory networks and various biological processes. Despite extensive research on this topic, its underlying mechanisms remain elusive, effective therapeutic approaches are yet to be established. Recent studies have shown that epigenetics play an important role in regulating skeletal muscle atrophy, influencing the numerous genes associated with condition through addition or removal certain chemical modifications at molecular level. This review article comprehensively summarizes different types DNA, histones, RNA, their known regulators. We also discuss how epigenetic change during process by which proteins control assess translational potential. The stem cells highlighted. In addition, we propose alternative splicing interacts regulate mass, offering novel perspective enhances our understanding inheritance’s network governing atrophy. Collectively, advancements provide invaluable insights into study Moreover, knowledge paves way for identifying new avenues development more strategies pharmaceutical interventions.

Language: Английский

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Unraveling precision exercise: A journey from efficacy to molecular insights

Advanced Exercise and Health Science, Journal Year: 2024, Volume and Issue: 1(1), P. 3 - 15

Published: Jan. 19, 2024

The swift acceleration of advances in precision medicine has attracted clinicians, health systems, and policymakers, thus leaving an indelible mark on the landscape medical practice. increasing acknowledgment shows rise a promising new field that can change practice provide care. Simultaneously, there is interest exercise, which refers to approach healthcare fitness where exercise regimens are tailored individual responses characteristics. Precision evolved as response understanding individuals exhibit wide range regimens, attributed genetic modifications other biological factors. purpose this article offer comprehensive evaluation basic principles, methods, practical applications exercise. Additionally, biomarkers serve pivotal indicators, bridging mechanisms with overall health. These insights into physiological responses, enabling customization optimize outcomes. Herein, underscores transformative potential revolutionizing personalized customized guided by based biomarkers. As continues evolve, stands at forefront, thereby future interventions uniquely for optimal

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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Methylome–proteome integration after late‐life voluntary exercise training reveals regulation and target information for improved skeletal muscle health

The Journal of Physiology, Journal Year: 2024, Volume and Issue: 603(1), P. 211 - 237

Published: July 26, 2024

Exercise is a potent stimulus for combatting skeletal muscle ageing. To study the effects of exercise on in preclinical setting, we developed combined endurance-resistance training mice called progressive weighted wheel running (PoWeR). PoWeR improves molecular, biochemical, cellular and functional characteristics promotes aspects partial epigenetic reprogramming when performed late life (22-24 months age). In this investigation, leveraged pan-mammalian DNA methylome arrays tandem mass-spectrometry proteomics to provide detailed information late-life adaptations female relative age-matched sedentary controls (n = 7-10 per group). Differential CpG methylation at conserved promoter sites was related transcriptional regulation genes as well Nr4a3, Hes1 Hox after PoWeR. Using holistic method -omics integration binding expression target analysis (BETA), changes were associated with upregulated proteins global mitochondrial translation (P 0.03). Specifically, BETA implicated control ribosomal, mitoribosomal, complex I protein abundance training. may also influence LACTB, MIB1 UBR4 induction - all are mechanistically linked health. Computational cistrome predicted several transcription factors including MYC regulators trained methylome-proteome landscape, corroborating prior transcriptome data. Correlating proteome mass fatigue resistance revealed positive relationships VPS13A NPL levels, respectively. Our findings expose differential proteomic translational that could function aged mice. KEY POINTS: Late-life from 22-24 age shown improve vivo promote mitigation. Integration 36k using (which contain ageing clock sites) exploratory extends our work reveals coordinated widespread initiation, ribosomal (mitoribosomal) voluntary sizeable cohort group analysis). Multi-omics serine β-lactamase-like (LACTB tumour muscle), mind bomb 1 (MIB1 satellite cell type 2 fibre maintenance) ubiquitin ligase E3 component N-recognin 4 (UBR4 quality control) identified regulator proteome, agreement analyses. Vacuolar sorting 13 homolog A (VPS13A) positively correlated mass, glycoprotein/glycolipid sialylation enzyme N-acetylneuraminate pyruvate lyase (NPL) resistance.

Language: Английский

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The 24-hour molecular landscape after exercise in humans reveals MYC is sufficient for muscle growth

EMBO Reports, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 31, 2024

Language: Английский

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Causal Relationship between Meat Intake and Biological Aging: Evidence from Mendelian Randomization Analysis

Nutrients, Journal Year: 2024, Volume and Issue: 16(15), P. 2433 - 2433

Published: July 26, 2024

Existing research indicates that different types of meat have varying effects on health and aging, but the specific causal relationships remain unclear. This study aimed to explore relationship between intake aging-related phenotypes. employed Mendelian randomization (MR) select genetic variants associated with from large genomic databases, ensuring independence pleiotropy-free nature these instrumental variables (IVs), calculated F-statistic evaluate strength IVs. The validity estimates was assessed through sensitivity analyses various MR methods (MR-Egger, weighted median, inverse-variance (IVW), simple mode, mode), MR-Egger regression intercept used test for pleiotropy bias Cochran's Q heterogeneity results. findings reveal a positive consumers DNA methylation PhenoAge acceleration, suggesting increased may accelerate biological aging process. Specifically, lamb is found effect mitochondrial copy number, while processed consumption shows negative telomere length. No significant were observed other intake. highlights impact processing cooking meat's role in enhancing our understanding how their preparation affect process, providing theoretical basis dietary strategies at delaying quality life.

Language: Английский

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