Systematic identification of exercise-induced anti-aging processes involving intron retention.

Hayata Kodama, Hirotaka Ijima, Yusuke Matsui
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Abstract

Exercise is one of the most promising anti-aging interventions for maintaining skeletal muscle health in older adults. Nine "Aging Hallmarks", proposed by López-Otín, offer insights into the aging process; however, the link between these hallmarks and exercise is not fully elucidated. In this study, we conducted a systematic multi-omics analysis of skeletal muscles, focusing on aging and exercise, based on gene signatures for aging hallmarks. It is posited that mRNA splicing activity, linked to genomic instability, constitutes a fundamental hallmark of aging, and exhibits divergent expression patterns in response to aging and exercise. Additionally, we analyzed splicing events and discovered that intron retention (IR) is significantly impacted by aging, exhibiting contrasting changes to those induced by resistance training in the older cohort. The isoforms characterized by IR are notably enriched in mitochondrial functions. Conclusively, our results underscore the significance of splicing mechanisms as a novel aspect of aging hallmarks in skeletal muscles and propose a new mechanism by which exercise exerts its anti-aging effects on skeletal muscles through IR.

系统鉴定运动诱导的涉及内含子保留的抗衰老过程。
锻炼是最有希望保持老年人骨骼肌健康的抗衰老干预措施之一。López-Otín提出的九个“衰老特征”提供了对衰老过程的见解;然而,这些特征和锻炼之间的联系还没有完全阐明。在这项研究中,我们对骨骼肌进行了系统的多组学分析,重点关注衰老和运动,基于衰老标志的基因特征。研究认为,与基因组不稳定性相关的mRNA剪接活性构成了衰老的基本标志,并在衰老和锻炼时表现出不同的表达模式。此外,我们分析了剪接事件,发现内含子保留(IR)受到年龄的显著影响,与老年队列中阻力训练引起的变化形成对比。IR表征的同工异构体在线粒体功能中显著富集。总之,我们的研究结果强调了拼接机制作为骨骼肌衰老标志的一个新方面的重要性,并提出了运动通过IR对骨骼肌发挥抗衰老作用的新机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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