Sarcosine decreases in sarcopenia and enhances muscle regeneration and adipose thermogenesis by activating anti-inflammatory macrophages.

Yu Liu, Meiling Ge, Xina Xiao, Ying Lu, Wanyu Zhao, Kun Zheng, Kexin Yu, Yanting He, Qian Zhong, Lixing Zhou, Shan Hai, Xiaohui Liu, Na Jiang, Dan Du, Yan Zhang, Guo Cheng, Zhenmei An, Yi Zhao, Heng Xu, Biao Dong, Shuangqing Li, Binwu Ying, Huiyuan Zhang, Jirong Yue, Birong Dong, Lunzhi Dai

National Clinical Research Center for Geriatrics and Department of Laboratory Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.National Clinical Research Center for Geriatrics and Department of Laboratory Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China. · pubmed

Paper

Abstract

Age-related changes in circulating metabolites influence systemic physiology and may contribute to diseases such as sarcopenia. Although metabolic dysregulation is closely linked to sarcopenia, the roles of specific metabolites remain unclear. In this study, we performed comprehensive plasma metabolomic and lipidomic analyses across two cohorts comprising 1,013 individuals, uncovering the metabolic characteristics of sarcopenia, including a notable decline in plasma sarcosine levels in both aging patients and those with sarcopenia. Functional studies in mice showed that sarcosine helps maintain muscle mass homeostasis during aging, promotes adipose thermogenesis and enhances muscle regeneration. We demonstrate here that sarcosine activated the GCN2 signaling pathway to enhance anti-inflammatory macrophage polarization, promoting adipose thermogenesis and muscle regeneration. These effects may increase energy expenditure and restore metabolic balance to reduce chronic inflammation and improve insulin sensitivity, which are crucial for managing sarcopenia. This study underscores the potential of sarcosine supplementation as an adjunctive strategy via macrophage modulation for preventing sarcopenia in older adults.

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Research summary

Sarcosine supplementation may enhance muscle regeneration and adipose thermogenesis by activating anti-inflammatory macrophages. The study addresses metabolic dysregulation in sarcopenia, which is a significant age-related condition, and explores a potential intervention that could mitigate its effects, thus contributing to longevity research.

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