Non-Coding RNAs in the Transcriptional Network That Differentiates Skeletal Muscles of Sedentary from Long-Term Endurance- and Resistance-Trained Elderly.

Paola De Sanctis,Alessandra Bolotta,Stefan Löfler,Marina Marini,Helmut Kern,Cinzia Zucchini,Provvidenza Maria Abruzzo,Annalisa Astolfi,Valentina Indio,Christian Hofer,Sandra Zampieri,Giuseppe Filardo,Alessandro Di Martino,Maurilio Marcacci

doi:10.3390/ijms22041539

Abstract

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 micro- 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 miRNA 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 lncRNAs, miRNAs and mRNAs, affecting processes in line with the beneficial role of exercise training.

Highlights

Sarcopenia is one of the most common ailments of older age and the main cause for frailty
By setting the statistical significance at Adj p Value < 0.05, no significant differences in their expression were found between subjects who practiced either endurance or resistance training (ET versus resistance trained (RT)), in analogy with what we described for mRNA
Among the eight “canonical” myomiRs, only miR-486 was differentially expressed between TRA and SED subjects, in particular both miR-486-3p and miR-486-5p were upregulated in TRA in comparison to SED, while other myomiRs were expressed in both groups, without statistically significant dif ferences between

Summary

Introduction

Sarcopenia is one of the most common ailments of older age and the main cause for frailty. We recently provided evidence of the fact that life-long high-level exercise training can offset most pathways leading to age-related sarcopenia by counteracting mitochondrial dysfunction, inflammation, cellular senescence, impairment of proteostatic mechanisms, and fostering an efficient use of energy. All these mechanisms were studied at the level of protein-coding gene expression and were found to be remarkably independent of the type of exercise training (endurance or resistance, ET or RT) [7]. Protein-coding gene expression was evaluated in light of the results obtained by Generation Sequence (NGS)

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