Emerging evidence suggests that circadian disruption and muscle wasting form a self-reinforcing loop

Abstract

Circadian disruption and skeletal muscle wasting frequently co-occur in critical illness, shift work, and aging. We propose a bidirectional self-reinforcing loop in which each process amplifies the other. Environmental disruption of the skeletal muscle clock impairs protein turnover and mitochondrial function, triggering atrophy. The resulting loss of muscle mass weakens peripheral clock output and disrupts systemic circadian rhythms. The forward arm is supported by genetic evidence, particularly from global Bmal1 knockout models and human sleep-deprivation studies. The reverse arm is supported by correlative evidence from clinical observations and disease models. Chronotherapeutic interventions targeting this loop have shown preclinical efficacy and warrant clinical translation.