Brain-muscle communication prevents muscle aging by maintaining daily physiology

Author:

Kumar Arun1ORCID,Vaca-Dempere Mireia1ORCID,Mortimer Thomas2ORCID,Deryagin Oleg1ORCID,Smith Jacob G.13ORCID,Petrus Paul34,Koronowski Kevin B.3ORCID,Greco Carolina M.35ORCID,Segalés Jessica1ORCID,Andrés Eva1,Lukesova Vera1,Zinna Valentina M.2ORCID,Welz Patrick-Simon6ORCID,Serrano Antonio L.17ORCID,Perdiguero Eusebio17ORCID,Sassone-Corsi Paolo3ORCID,Benitah Salvador Aznar28ORCID,Muñoz-Cánoves Pura178ORCID

Affiliation:

1. Department of Medicine and Life Sciences (MELIS), Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain.

2. Institute for Research in Biomedicine (IRB), Barcelona, The Barcelona Institute of Science and Technology, 08028 Barcelona, Spain.

3. Department of Biochemistry & Structural Biology, Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health San Antonio, San Antonio, TX 78229, USA.

4. Department of Medicine (H7), Karolinska Institutet, Stockholm 141 86, Sweden.

5. Department of Biomedical Sciences, Humanitas University and Humanitas Research Hospital IRCCS, 20089, Rozzano (Milan), Italy.

6. Cancer Research Programme, Hospital del Mar Medical Research Institute (IMIM), 08003 Barcelona, Spain.

7. Altos Labs Inc., San Diego Institute of Science, San Diego, CA 92121, USA.

8. Catalan Institution for Research and Advanced Studies (ICREA), 08010 Barcelona, Spain.

Abstract

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.

Publisher

American Association for the Advancement of Science (AAAS)

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