Aberrant expression of thyroidal hormone receptor α exasperating mitochondrial dysfunction induced sarcopenia in aged mice

• DOI: 10.18632/aging.205748
• Publication Date: 2024-04-18T16:01:55Z
• Authors: Yunlu Sheng; Xiaoxia Zhu; Lijun Wei; Yuxin Zou; Xinyu Qi; Runqing Shi; Wenli Xu; Xiaodong Wang; Guoxian Ding; Yu Duan
• Keywords: PINK1; C2C12

Disrupted mitochondrial dynamics and mitophagy contribute to functional deterioration of skeletal muscle (SM) during aging, but the regulatory mechanisms are poorly understood. Our previous study demonstrated that expression thyroid hormone receptor α (TRα) decreased significantly in aged mice, suggesting alteration thyroidal elements, especially TRα, might attenuate local THs action thus cause degeneration SM with while underlying mechanism remains be further explored. In this study, myogenic regulators Myf5, MyoD1, markers Pink1, LC3II/I, p62, as well dynamic factors Mfn1 Opa1, accompanied by increased reactive oxygen species (ROS), showed concomitant changes reduced TRα mice. Further loss- gain-of-function studies C2C12 revealed silencing not only down-regulated above-mentioned regulators, factors, also led a significant decrease activity maximum respiratory capacity, more ROS damaged mitochondria. Notedly, overexpression could up-regulate those meanwhile an increase number. These results confirmed concertedly regulate dynamics, autophagy, activity, rhythmically altered expression. Summarily, these suggested decline aging regulating myogenesis.