The hypothalamic-pituitary-gonadal axis controls muscle stem cell senescence through autophagosome clearance

Autor: Kim, Ji-Hoon, Park, Inkuk, Shin, Hijai R, Rhee, Joonwoo, Seo, Ji-Yun, Jo, Young-Woo, Yoo, Kyusang, Hann, Sang-Hyeon, Kang, Jong-Seol, Park, Jieon, Kim, Ye Lynne, Moon, Ju-Yeon, Choi, Man Ho, Kong, Young-Yun
Rok vydání: 2021
Předmět:
Zdroj: Journal of cachexia, sarcopenia and muscle, vol 12, iss 1
Popis: BackgroundWith organismal aging, the hypothalamic-pituitary-gonadal (HPG) activity gradually decreases, resulting in the systemic functional declines of the target tissues including skeletal muscles. Although the HPG axis plays an important role in health span, how the HPG axis systemically prevents functional aging is largely unknown.MethodsWe generated muscle stem cell (MuSC)-specific androgen receptor (Ar) and oestrogen receptor 2 (Esr2) double knockout (dKO) mice and pharmacologically inhibited (Antide) the HPG axis to mimic decreased serum levels of sex steroid hormones in aged mice. After short-term and long-term sex hormone signalling ablation, the MuSCs were functionally analysed, and their aging phenotypes were compared with those of geriatric mice (30-month-old). To investigate pathways associated with sex hormone signalling disruption, RNA sequencing and bioinformatic analyses were performed.ResultsDisrupting the HPG axis results in impaired muscle regeneration [wild-type (WT) vs. dKO, P 
Databáze: OpenAIRE