Chronic circadian misalignment accelerates sarcopenia progression in mice

In today's 24/7 society, circadian misalignment caused by environmental and lifestyle factors is associated with various adverse health consequences, underscoring the need to understand tissue-specific pathology. A potential association of environmental circadian misalignment with sarcopenia, or accelerated loss of skeletal muscle strength and mass, is poorly documented. Here, we exposed wild-type C57BL/6J male mice to a chronic (64 weeks) jet lag (CJL) paradigm. CJL caused significant reductions in muscle strength and weight relative to untreated mice. Transcriptomic and histological analysis showed activation of TWEAK/Fn14 signaling and reduced myofiber cross-sectional area, hallmark features of sarcopenia. Furthermore, CJL mice showed increased centrally nucleated fibers, myosin heavy chain co-expressing fibers, and myogenic gene expression, suggesting that insufficient muscle regeneration likely contributes to muscle atrophy. These findings demonstrate that circadian misalignment is an independent risk factor for sarcopenia, underscoring circadian rhythms as a key regulator and actionable target for sarcopenia prevention. Overall design: Examination of poly(A)+ enriched RNAs in mouse gastrocnemius muscle exposed to chronic circadian misalignment in addition to control. Wild-type male C57BL/6J mice were exposed to chronic jet lag characterized by 8-hour advance every 4 days (referred to as ADV paradigm) for 64 weeks, whereas the control group (LD) were maintained under the normal 12h:12h light-dark condition.