Mechanism of thyroid hormone signaling in skeletal muscle of aging mice.

Abstract

Skeletal muscle (SM) has been shown as a target of thyroid hormones (THs). However, the status of TH signaling in aged SM remains unclear. This study aimed to explore the mechanism of TH signaling in SM of aging mice. Thirty C57BL/6J male mice were divided into 6-, 15- and 22-month (6, 15 and 22M) groups according to different age. Physical parameters were evaluated by analytical balance, grip strength test and histological analysis. Thyroid function was detected by enzyme-linked immunosorbent assay. TH signaling was compared among the three groups by real-time PCR and western blotting analysis. p16, p21, and p53 mRNA levels in SM increased in age-dependent manner. The muscle weight and strength decreased in 22M group compared to 6 and 15M groups. Concentrations of thyroid hormones, including free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) in 22 M mice were not shown significant difference compared to 6M or 15M mice, although FT3 showed slightly decrease and TSH appeared a mild increase accompanying with age. mRNA levels of TH transporters, including MCT8 and MCT10, as well as iodothyronine deiodinase type 2 (DIO2) and type 3 (DIO3), were higher in 22M, while TH receptor α (TRα) mRNA and protein expression was lower in 22M, compared to the other groups. Type-I myosin heavy chain (MyHC I), MyHC IIx, and MyHC IIa were upregulated and Type-IIb MyHC (MyHC IIb) was downregulated in SM with advancing age. TH signaling in SM changes with aging.