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

Background With 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 prevent...

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Bibliographic Details
Published in:Journal of cachexia, sarcopenia and muscle sarcopenia and muscle, 2021-02, Vol.12 (1), p.177-191
Main Authors: 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
Format: Article
Language:English
Subjects:
Aging
Androgens
Antibodies
Autophagy
Cell culture
Cellular senescence
Cloning
Geriatrics
Hormones
Laboratories
Muscle regeneration
Muscle stem cell
Musculoskeletal system
Original
Phenols
Physiology
Puberty
Senescence
Sex steroid hormones
Stem cells
Transgenic animals
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Summary:Background With 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. Methods We 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. Results Disrupting the HPG axis results in impaired muscle regeneration [wild‐type (WT) vs. dKO, P 
ISSN:2190-5991
2190-6009
DOI:10.1002/jcsm.12653