Abstract

Aging induces gradual accumulation of damages in cells and tissues, which leads to physiological dysfunctions. Aging-associated muscle dysfunction is commonly seen in aged population and severely affects their physical activity and life quality, against which aerobic training has been shown to exert antagonizing or alleviating effects. Circular RNAs (circRNAs) play important roles in various physiological processes, yet their involvement in aging-associated muscle dysfunction is not well understood. In this study, we performed comprehensive analysis of circRNAs profiles in quadriceps muscles in sedentary young and aging mice, as well as aging mice with aerobic exercise using RNA sequencing. Our results identified circRNAs altered by factors of aging and aerobic exercise. Their host genes were then predicted and analyzed by gene ontology enrichment analysis. Importantly, we found that circBBS9 featured decreased levels in aging compared to young mice and elevated expression in exercise versus sedentary aging mice. Besides, we performed GO and KEGG analysis on circBBS9 target genes, as well as established the circBBS9-miRNA-mRNAs interaction network. Our results indicate that circBBS9 may play active roles in muscle aging by mediating the benefits of aerobic training intervention, thus may serve as a novel therapeutic target combating aging-associated muscle dysfunction.

Highlights

  • An increase in life expectancy in modern world brings an ‘aged society’, in which a substantial aging population poses challenges both medically and financially [1, 2]

  • To access the extents of muscle dysfunction, six muscle samples per group from mice of young, aging and aging plus aerobic exercise were examined for gene markers indicative of mitochondrial homeostasis and muscle atrophy

  • We firstly investigated the differential Circular RNA (circRNA) in quadriceps muscle between young and aging group, which may be used as biomarkers for aging-associated muscle dysfunction

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Summary

Introduction

An increase in life expectancy in modern world brings an ‘aged society’, in which a substantial aging population poses challenges both medically and financially [1, 2]. Aging is defined as the age-dependent physiological decline that affects all living organisms. Aging undermines multiple major organs and plays a profound role in the onset of neurodegenerative diseases, cardiovascular diseases, metabolic disorders, as well as a loss in muscle and bone mass [3,4,5,6,7]. Metabolic fitness emerges as a novel player in the arena of combating aging. Metabolic interventions, such as caloric restriction, intermittent fasting and exercise, confer multiple health benefits ranging from stronger skeleton muscle and cardiac function to improved metabolic fitness and cognitive functions, and most importantly, increased lifespan in multiple species [12, 13]

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