Dynamic changes in butyrate levels regulate satellite cell homeostasis by preventing spontaneous activation during aging  

作　　者：Shujie Chen Liujing Huang Bingdong Liu Huimin Duan Ze Li Yifan Liu Hu Li Xiang Fu Jingchao Lin Yinlan Xu Li Liu Dan Wan Yulong Yin Liwei Xie 

机构地区：[1]Department of Endocrinology and Metabolism,Zhujiang Hospital,Southern Medical University,Guangzhou 510280,China [2]State Key Laboratory of Applied Microbiology Southern China,Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application,Guangdong Open Laboratory of Applied Microbiology,Institute of Microbiology,Guangdong Academy of Sciences,Guangzhou 510070,China [3]School of Public Health,Xinxiang Medical University,Xinxiang 453003,China [4]Department of Infectious Diseases,Nanfang Hospital,Southern Medical University,Guangzhou 510515,China [5]Metabo-Profile Biotechnology(Shanghai)Co.Ltd.,Shanghai 201315,China [6]Institute of Aging Research,Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics,School of Medical Technology,Guangdong Medical University,Dongguan 524023,China [7]Department of Rehabilitation Medicine,Nanfang Hospital,Southern Medical University,Guangzhou 510000,China [8]Laboratory of Animal Nutritional Physiology and Metabolic Process,Key Laboratory of Agro-ecological Processes in Subtropical Region,Institute of Subtropical Agriculture,Chinese Academy of Sciences,Changsha 410125,China [9]Bioland Laboratory,Guangzhou Regenerative Medicine and Health Guangdong Laboratory,Guangzhou 510005,China

出　　处：《Science China(Life Sciences)》2024年第4期745-764,共20页中国科学（生命科学英文版）

基　　金：supported by the Guangdong Basic and Applied Basic Research Foundation(2020B1515020046);“GDAS”Project of Science and Technology Development(2021GDASYL20210102003,2018GDASCX-0102);the National Natural Science Foundation of China(82072436,32130099);Open Program of Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics(GPKLMMD-OP202102);Outstanding Youth Fund of Hunan Natural Science Foundation(2021JJ20045);the Outstanding Youth Fund of Hunan Natural Science Foundation(2021JJ20045);Youth Innovation Promotion Association of Chinese Academy of Sciences(2022370)。

摘　　要：The gut microbiota plays a pivotal role in systemic metabolic processes and in particular functions,such as developing and preserving the skeletal muscle system.However,the interplay between gut microbiota/metabolites and the regulation of satellite cell(SC)homeostasis,particularly during aging,remains elusive.We propose that gut microbiota and its metabolites modulate SC physiology and homeostasis throughout skeletal muscle development,regeneration,and aging process.Our investigation reveals that microbial dysbiosis manipulated by either antibiotic treatment or fecal microbiota transplantation from aged to adult mice,leads to the activation of SCs or a significant reduction in the total number.Furthermore,employing multi-omics(e.g.,RNA-seq,16S r RNA gene sequencing,and metabolomics)and bioinformatic analysis,we demonstrate that the reduced butyrate levels,alongside the gut microbial dysbiosis,could be the primary factor contributing to the reduction in the number of SCs and subsequent impairments during skeletal muscle aging.Meanwhile,butyrate supplementation can mitigate the antibiotics-induced SC activation irrespective of gut microbiota,potentially by inhibiting the proliferation and differentiation of SCs/myoblasts.The butyrate effect is likely facilitated through the monocarboxylate transporter 1(Mct1),a lactate transporter enriched on membranes of SCs and myoblasts.As a result,butyrate could serve as an alternative strategy to enhance SC homeostasis and function during skeletal muscle aging.Our findings shed light on the potential application of microbial metabolites in maintaining SC homeostasis and preventing skeletal muscle aging.

关 键 词：gut microbiota AGING satellite cells BUTYRATE Slc16a1(Mct1) 

分 类 号：R339.38[医药卫生—人体生理学]