Proteasome stress in skeletal muscle mounts a long-range protective response that delays retinal and brain aging

Rai M, Coleman Z, Curley M, Nityanandam A, Platt A, Robles-Murguia M, Jiao, J, Finkelstein D, Wang Y-D, Xu B, Fan Y, Demontis F.

Cell Metabolism, 2021



The peripheral nervous system is known to influence central nervous system (CNS) aging and neurodegeneration but the underlying mechanism is unexplored.  The authors found that skeletal muscle stress resulted in compensatory preservation of CNS proteostasis during aging. Long-range stress signaling depended on the muscle released Amyrel amylase that preserved proteins in the brain and retina via chaperones.  The effect of maltose preservation of proteostasis and neuronal activity was assessed with human brain organoids challenged with thermal stress.