Kumar Arun, Vaca-Dempere Mireia, Mortimer Thomas, Deryagin Oleg, Smith Jacob G, Petrus Paul, Koronowski Kevin B, Greco Carolina M, Segalés Jessica, Andrés Eva, Lukesova Vera, Zinna Valentina M, Welz Patrick-Simon, Serrano Antonio L, Perdiguero Eusebio, Sassone-Corsi Paolo, Benitah Salvador Aznar, Muñoz-Cánoves Pura
Department of Medicine and Life Sciences (MELIS), Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain.
Institute for Research in Biomedicine (IRB), Barcelona, The Barcelona Institute of Science and Technology, 08028 Barcelona, Spain.
Science. 2024 May 3;384(6695):563-572. doi: 10.1126/science.adj8533. Epub 2024 May 2.
A molecular clock network is crucial for daily physiology and maintaining organismal health. We examined the interactions and importance of intratissue clock networks in muscle tissue maintenance. In arrhythmic mice showing premature aging, we created a basic clock module involving a central and a peripheral (muscle) clock. Reconstituting the brain-muscle clock network is sufficient to preserve fundamental daily homeostatic functions and prevent premature muscle aging. However, achieving whole muscle physiology requires contributions from other peripheral clocks. Mechanistically, the muscle peripheral clock acts as a gatekeeper, selectively suppressing detrimental signals from the central clock while integrating important muscle homeostatic functions. Our research reveals the interplay between the central and peripheral clocks in daily muscle function and underscores the impact of eating patterns on these interactions.
分子时钟网络对于日常生理功能和维持机体健康至关重要。我们研究了组织内时钟网络在肌肉组织维持中的相互作用及其重要性。在表现出早衰的心律失常小鼠中,我们构建了一个包含中央时钟和外周(肌肉)时钟的基本时钟模块。重建脑-肌肉时钟网络足以维持基本的日常稳态功能并预防肌肉早衰。然而,要实现整个肌肉的生理功能还需要其他外周时钟的参与。从机制上讲,肌肉外周时钟充当守门人,在整合重要的肌肉稳态功能时选择性地抑制来自中央时钟的有害信号。我们的研究揭示了中央时钟和外周时钟在日常肌肉功能中的相互作用,并强调了饮食模式对这些相互作用的影响。