Transcriptional Differences in Non-Coding RNA Between Fit and Sedentary Elderly People

Structured exercise programs cause sweeping beneficial changes in metabolism and the transcriptional landscape of cells in older individuals. Health improves, mortality is reduced, numerous measures of the aging of muscle tissue slowed. Researchers here look at one small slice of this bigger picture, the activity of non-coding RNAs in muscle tissue. These molecules are produced via transcription from genetic blueprints, but are not translated into functional proteins. Instead they largely appear to influence the process of translation of other RNA molecules into proteins. This class of RNA molecule is far from fully catalogued or understood, and there are likely functions yet to be discovered and catalogued.

In a previous study, the whole transcriptome of the vastus lateralis muscle from sedentary elderly and from age-matched athletes with an exceptional record of high-intensity, life-long exercise training was compared - the two groups representing the two extremes on a physical activity scale. Exercise training enabled the skeletal muscle to counteract age-related sarcopenia by inducing a wide range of adaptations, sustained by the expression of protein-coding genes involved in energy handling, proteostasis, cytoskeletal organization, inflammation control, and cellular senescence. Building on the previous study, we examined here the network of non-coding RNAs participating in the orchestration of gene expression and identified differentially expressed microRNAs and long-non-coding RNAs and some of their possible targets and roles.

Unsupervised hierarchical clustering analyses of all non-coding RNAs were able to discriminate between sedentary and trained individuals, regardless of the exercise typology. Validated targets of differentially expressed microRNA were grouped by KEGG analysis, which pointed to functional areas involved in cell cycle, cytoskeletal control, longevity, and many signaling pathways, including AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR), which had been shown to be pivotal in the modulation of the effects of high-intensity, life-long exercise training. The analysis of differentially expressed long-non-coding RNAs identified transcriptional networks, involving long-non-coding RNAs, microRNAs and messenger RNAs, affecting processes in line with the beneficial role of exercise training.



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