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Chronic circadian misalignment accelerates sarcopenia progression in mice.

Takashi Seya1,2, Nobuya Koike1, Naoki Okubo1,2

  • 1Department of Physiology and Systems Bioscience, Kyoto Prefectural University of Medicine, Kyoto, Japan.

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|December 1, 2025
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Summary

Chronic jet lag accelerates muscle loss and weakness, indicating circadian misalignment is a risk factor for sarcopenia. This highlights circadian rhythms as a target for preventing age-related muscle decline.

Keywords:
TWEAK/Fn14 signalingcircadian misalignmentcircadian rhythmfrailtysarcopeniaskeletal muscle

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Area of Science:

  • Chronobiology
  • Muscle Physiology
  • Aging Research

Background:

  • Circadian misalignment from lifestyle factors is linked to adverse health outcomes.
  • Sarcopenia, the loss of muscle strength and mass, is a growing public health concern.
  • The relationship between circadian disruption and sarcopenia is not well understood.

Purpose of the Study:

  • To investigate the impact of chronic circadian misalignment on skeletal muscle health.
  • To determine if chronic jet lag induces sarcopenia-like changes in mice.

Main Methods:

  • Mice were subjected to chronic jet lag (ADV group) or a fixed light-dark cycle (LD group) for 64 weeks.
  • Grip strength, hindlimb muscle weight, and muscle histology were assessed.
  • Transcriptomic analysis of hindlimb muscles was performed.

Main Results:

  • Chronic jet lag significantly reduced grip strength and muscle weight.
  • Histological and transcriptomic analyses revealed sarcopenia hallmarks, including TWEAK/Fn14 signaling activation and reduced myofiber size.
  • Evidence of compensatory muscle regeneration was observed but insufficient to prevent atrophy.

Conclusions:

  • Circadian misalignment is a potential risk factor for sarcopenia.
  • Circadian rhythms are critical regulators of muscle health and represent a target for sarcopenia prevention strategies.