Reactive oxygen species (ROS) and MyomiRs dysregulation in aged human satellite cells

Abstract

Sarcopenia is the age-related loss of muscle mass and function. The muscle regeneration is promoted by satellite cells (SC), muscle stem cells. After injury or different stimuli, local signals induce SC proliferation and differentiation for tissue repair, in young subjects. On the contrary, in elderly subjects, intrinsic stem-cell aging, aging of the niche or systemic environment, induce a reduced SC functionality, determining a difficulty to term the differentiation program1,2. This difficulty could be due to several factors (that may be related to each other) such as oxidative stress accumulation3, failure of the activation of myogenic transcriptional factors (MRFs) together with miRNA deregulation. To achieve this, we investigated in myoblasts and myotubes derived from human Vastus Lateralis skeletal muscle of young and old subjects: i)muscle specific miRNAs (MyomiRs) expression; ii)rtq-PCR for MRFs; iii)O2•- and ROS levels and direct O2•- measurement in mitochondria through MitoSOX™ Red; iv)DYmit after oxidant insult (H2O2); v)Hsp60 and Hsp70 WB. We found deregulation of MRFs and MyomiRs, up-regulation of ROS level, and DYmit decrease in elderly SC. The data obtained suggest an involvement of ROS and specific myomiRs, interfering negatively with myogenic differentiation cooperating to the atrophic state that characterizes muscle ageing.