Faculty, Staff and Student Publications

Language

English

Publication Date

1-1-2025

Journal

Frontiers in Physiology

DOI

10.3389/fphys.2025.1686942

PMID

41321491

PMCID

PMC12658988

PubMedCentral® Posted Date

11-13-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Introduction: In today's 24/7 society, circadian misalignment caused by environmental and lifestyle factors is associated with various adverse health consequences. Understanding tissue-specific pathology is required to counter this growing public health challenge. A potential association of environmental circadian misalignment with sarcopenia, or accelerated loss of skeletal muscle strength and mass, is poorly documented.

Methods: 14-week-old wild-type C57BL/6J male mice were exposed to a chronic jet lag (CJL) paradigm consisting of an 8-h phase advance every 4 days (the ADV group) or a fixed light-dark cycle (the LD group) for 64 weeks. Grip strength was measured during the experiment, and hindlimb muscle weight was assessed after the 64-week CJL. In addition, transcriptomic and histological analysis of the hindlimb muscles were performed in all animals.

Results: ADV mice exhibited significant reductions in grip strength and muscle weight relative to LD mice. Transcriptomic and histological analyses showed activation of TWEAK/Fn14 signaling and reduced myofiber cross-sectional area, hallmark features of sarcopenia, in the ADV group. Somewhat surprisingly, ADV mice showed increased centrally nucleated fibers, myosin heavy chain co-expressing fibers, and myogenic gene expression, suggesting that compensatory muscle regeneration and remodeling processes are activated but remain insufficient to counter muscle atrophy.

Conclusion: These findings demonstrate that circadian misalignment is a potential risk factor for sarcopenia, underscoring circadian rhythms as a key regulator and actionable target for sarcopenia prevention.

Keywords

circadian rhythm, circadian misalignment, sarcopenia, frailty, skeletal muscle, TWEAK/Fn14 signaling

Published Open-Access

yes

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