Decrease in the expression of muscle-specific miRNAs, miR-133a and miR-1, in myoblasts with replicative senescence

• Published in: PloS one 2023-01, Vol.18 (1), p.e0280527-e0280527
• Main Authors: Shintani-Ishida, Kaori, Tsurumi, Riko, Ikegaya, Hiroshi
• Format: Article
• Language: English
• Subjects: Aging; Animals; Antibodies; Atrophy, Muscular; Biology and life sciences; Care and treatment; Cell differentiation; Cell Differentiation - genetics; Cell fusion; Cells; Cellular Senescence - genetics; Cloning; Development and progression; Differentiation; Gene expression; Glutaminase; Health aspects; Laboratories; Male; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; MicroRNA; MicroRNAs; MicroRNAs - metabolism; miRNA; Muscle Development - genetics; Muscle Fibers, Skeletal - metabolism; Muscles; Musculoskeletal system; Myoblasts; Myoblasts, Skeletal - metabolism; Myotubes; Physiological aspects; Regeneration; Research and Analysis Methods; Risk factors; Senescence; Transfection
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0280527

Muscles that are injured or atrophied by aging undergo myogenic regeneration. Although myoblasts play a pivotal role in myogenic regeneration, their function is impaired with aging. MicroRNAs (miRNAs) are also involved in myogenic regeneration. MiRNA (miR)-1 and miR-133a are muscle-specific miRNAs that control the proliferation and differentiation of myoblasts. In this study, we determined whether miR-1 and miR-133a expression in myoblasts is altered with cellular senescence and involved in senescence-impaired myogenic differentiation. C2C12 murine skeletal myoblasts were converted to a replicative senescent state by culturing to a high passage number. Although miR-1 and miR-133a expression was largely induced during myogenic differentiation, expression was suppressed in cells at high passage numbers (passage 10 and/or passage 20). Although the senescent myoblasts exhibited a deterioration of myogenic differentiation, transfection of miR-1 or miR-133a into myoblasts ameliorated cell fusion. Treatment with the glutaminase 1 inhibitor, BPTES, removed senescent cells from C2C12 myoblasts with a high passage number, whereas myotube formation and miR-133a expression was increased. In addition, primary cultured myoblasts prepared from aged C57BL/6J male mice (20 months old) exhibited a decrease in miR-1 and miR-133a levels compared with younger mice (3 months old). The results suggest that replicative senescence suppresses muscle-specific miRNA expression in myoblasts, which contributes to the senescence-related dysfunction of myogenic regeneration.