Subchronic Arsenite Exposure Accelerated Skeletal Muscle Aging With Abnormal Corticosterone Secretion in Middle‐Aged Mice

It has indicated that arsenic exhibits toxicity to skeletal muscle; however, the specific characteristics of arsenic-induced skeletal muscle damage and associated risk indicators remain unclear. Our previous research has demonstrated that arsenite-induced skeletal muscle atrophy exhibits a susceptibility in middle-aged rats, and other studies have shown that glucocorticoids play a significant role in maintaining skeletal muscle mass. This study was aimed at investigating the relationship between alterations in serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels and indicators of arsenic-induced skeletal muscle aging in mice. In this study, 24 male C57BL/6J mice were randomly assigned to a control group and three arsenite exposure groups with low dose (0.01 mg/L), medium dose (0.1 mg/L), and high dose (1 mg/L). The results showed that in the 0.1 and 1 mg/L arsenite exposure groups compared to the control group, a shortening in relative telomere length and a decreased ratio of type II/I myofibers were observed in the gastrocnemius muscle. Additionally, serum levels of ACTH and CORT were elevated, alongside increased indicators of oxidative stress (SOD, GSH, and MDA) as well as inflammatory factors (TNF-α, IL-1β, and IL-6) within the gastrocnemius muscle. In addition, mice exposed to 1 mg/L arsenite exhibited a significant decline in limb grip strength and skeletal muscle atrophy. The serum levels of ACTH and CORT in arsenite exposure groups exhibited a significant negative correlation with limb grip strength, gastrocnemius muscle index, and the relative length of telomeres in the gastrocnemius muscle. This study demonstrated that long-term exposure to arsenite could accelerate skeletal muscle aging in middle-aged mice, potentially linked to the dysregulation of the HPA axis.