小柯机器人

美国斯坦福大学医学院Thomas A. Rando团队近期取得重要工作进展，他们研究发现禁食通过酮体信号诱导肌肉干细胞进入高弹性深静息状态。相关研究成果2022年5月17日在线发表于《细胞—代谢》杂志上。

在这里，研究人员报告说，禁食会减缓肌肉修复，无论是在禁食立马结束后，还是在多天的再进食后。他们表明，无论是在禁食或生酮饮食期间内源性产生的酮症，还是外源性给予的酮症，都能促进肌肉干细胞（MuSCs）的深度静息状态。尽管深度静息的MuSC不太容易被激活，减缓了肌肉细胞再生，但它们在面临细胞压力时显著提高了存活率。

此外，研究人员表明酮体，特别是β-羟基丁酸，通过非代谢机制直接促进MuSC深度静息。他们发现β-羟基丁酸盐在MuSCs中起到HDAC抑制剂的作用，导致HDAC1靶蛋白p53的乙酰化和活化。最后，他们表明p53激活有助于在禁食期间观察到深度静息和恢复力的增强。

据介绍，短期禁食有利于多种组织类型的再生。然而，禁食对肌肉再生的影响在很大程度上是未知的。

附：英文原文

Title: Fasting induces a highly resilient deep quiescent state in muscle stem cells via ketone body signaling

Author: Daniel I. Benjamin, Pieter Both, Joel S. Benjamin, Christopher W. Nutter, Jenna H. Tan, Jengmin Kang, Leo A. Machado, Julian D.D. Klein, Antoine de Morree, Soochi Kim, Ling Liu, Hunter Dulay, Ludovica Feraboli, Sharon M. Louie, Daniel K. Nomura, Thomas A. Rando

Issue&Volume: 2022-05-17

Abstract: Short-term fasting is beneficial for the regeneration of multiple tissue types. However,the effects of fasting on muscle regeneration are largely unknown. Here, we reportthat fasting slows muscle repair both immediately after the conclusion of fastingas well as after multiple days of refeeding. We show that ketosis, either endogenouslyproduced during fasting or a ketogenic diet or exogenously administered, promotesa deep quiescent state in muscle stem cells (MuSCs). Although deep quiescent MuSCsare less poised to activate, slowing muscle regeneration, they have markedly improvedsurvival when facing sources of cellular stress. Furthermore, we show that ketonebodies, specifically β-hydroxybutyrate, directly promote MuSC deep quiescence viaa nonmetabolic mechanism. We show that β-hydroxybutyrate functions as an HDAC inhibitorwithin MuSCs, leading to acetylation and activation of an HDAC1 target protein p53.Finally, we demonstrate that p53 activation contributes to the deep quiescence andenhanced resilience observed during fasting.

DOI: 10.1016/j.cmet.2022.04.012

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00182-6

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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