Abstract
Aging significantly affects the cardiac muscle (CM) and skeletal muscles (SM). Since the aging process of CM and SM may be different, high throughput RNA sequencing was performed using CM and SM in different age conditions to evaluate the expression profiles of messenger RNA (mRNA), long non-coding RNA (lncRNA), micro RNA (miRNA), and circular (circRNA). Several mRNAs, lncRNAs, and miRNAs were highly expressed and consistently appeared in both ages in one of the two muscle tissues. Gene ontology (GO) annotation described that these genes were required for maintaining normal biological functions of CM and SM tissues. Furthermore, 26 mRNAs, 4 lncRNAs, 22 miRNAs, and 26 circRNAs were differentially expressed during cardiac muscle aging. Moreover, 81 mRNAs, 5 lncRNAs, 79 miRNAs, and 62 circRNAs were differentially expressed during aging of skeletal muscle. When comparing the expression profiles of CM and SM during aging, the senescence process in CM and SM was found to be fundamentally different. In addition, we assessed multi-group cooperative control relationships and constructed circRNA-miRNA-mRNA co-expression networks in muscular aging. In conclusion, our findings will contribute to the understanding of muscular aging and provide a foundation for future studies on the molecular mechanisms underlying muscular aging.
Highlights
Aging affects the body’s tissues in all organisms and is a major risk factor for the development of many diseases
We found that the genes enriched for “defense response to virus”, such as ubiquitin-like modifier (ISG15), interferon induced protein with tetratricopeptide repeats 3 (IFIT3), interferon induced protein with tetratricopeptide repeats 1 (IFIT1) (Supplementary Dataset 4), showed higher expression levels in old skeletal muscle (OSM) compared to young skeletal muscle (YSM)
62 DECs were identified in skeletal muscles (SM) of which 40 circRNAs were up-regulated while 22 circRNAs down-regulated (Supplementary 3D, Supplementary Dataset 4). In these DECs, we found that 3 circRNAs (circRNA020877, circRNA020853, Figure 4: Differentially expressed long non-coding RNA (lncRNA) during aging. (A) Differentially expressed lncRNAs in old cardiac muscle vs. young cardiac muscle (OYCM). (B) Differentially expressed lncRNAs in old skeletal muscle vs. young skeletal muscle (OYSM)
Summary
Aging affects the body’s tissues in all organisms and is a major risk factor for the development of many diseases. Aging is characterized by the progressive functional decline of several organs and tissues, that eventually causes death [2]. It affects physical appearance of the body and alters the expression of age-related genes [3]. In previous studies, aging-related messenger RNAs (mRNAs) were identified by analyzing the genomewide transcriptome in humans and other mammals [4,5,6]. In some studies, the regulatory mechanisms of miRNAs [10,11,12] and lncRNAs [13, 14] were reported in aging mammals. CircRNAs may play an important role in the regulation of aging
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