Brain–muscle tissue communication prevents muscle aging by maintaining daily physiology

A network of molecular clocks is crucial for coordinating daily physiology and maintaining organismal health. However, the mechanisms underlying the interactions between these clocks and the significance of intra-tissue clock networks in muscle tissue maintenance have remained elusive. To uncover this network structure, we established a minimal clock module with the central clock (suprachiasmatic nucleus/brain) and/or a peripheral clock (muscle) in arrhythmic mice with premature aging. We find that reconstituting the brain-muscle clock network alone is sufficient to preserve fundamental daily homeostatic functions and prevent premature muscle aging. However, achieving whole muscle daily physiology requires the contribution of other peripheral clocks. Mechanistically, the muscle peripheral clock acts as a gatekeeper, selectively suppressing signals from the central clock that could be detrimental to muscle function if left uncontrolled while also integrating important muscle homeostatic functions. Our findings unveil the reciprocal interactions between central and peripheral clocks crucial for daily muscle function and highlight the significant influence of eating patterns on these interactions. These insights have implications for promoting healthier aging and reversing age-related muscle pathologies.