Ileal FXR-FGF15/19 signaling activation improves skeletal muscle loss in aged mice

  • Mech Ageing Dev. 2022 Mar;202:111630. doi: 10.1016/j.mad.2022.111630.
Yixuan Qiu  1 ,  Jiaming Yu  1 ,  Xueying Ji  1 ,  Huiyuan Yu  1 ,  Mengjuan Xue  1 ,  Fan Zhang  1 ,  Yi Li  2 ,  Zhijun Bao  3
Affiliations
  • 1. Department of Gerontology, Huadong Hospital Affiliated to Fudan University, Shanghai, 200000, China; Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai, 200000, China; Research Center on Aging and Medicine, Fudan University, Shanghai, 200000, China.
  • 2. Department of Geriatrics, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510000, China. Electronic address: [email protected].
  • 3. Department of Gerontology, Huadong Hospital Affiliated to Fudan University, Shanghai, 200000, China; Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai, 200000, China; Research Center on Aging and Medicine, Fudan University, Shanghai, 200000, China. Electronic address: [email protected].
PMID: 35026209 DOI: 10.1016/j.mad.2022.111630
Abstract

Sarcopenia is the age-related decrease in skeletal muscle mass, and current therapies for this disease are ineffective. We previously showed that ileal farnesoid X receptor (FXR)-fibroblast growth factor 15/19 (FGF15/19) signaling acts as a regulator of gut microbiota to mediate host skeletal muscle. However, the therapeutic potential of this pathway for sarcopenia is unknown. This study showed that ileal FXR-FGF15/19 signaling was downregulated in older men and aged male mice due to changes in the gut microbiota and microbial bile acid metabolism during aging. In addition, the intestine-specific FXR Agonist fexaramine increased skeletal muscle mass and improve muscle performance in aged mice. Ileal FXR activation increased skeletal muscle protein synthesis in a FGF15/19-dependent way, indicating that ileal FXR-FGF15/19 signaling is a potential therapeutic target for sarcopenia.

Keywords
Bile acid; FGF15/19; FXR; Fexaramine; Skeletal muscle.
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