Aging-Related Muscle Bmal1 Decline Contributes to Bone Loss in Mice via Enhancing IL-1α-Mediated Osteoclastogenesis

Area of Science:

• Gerontology
• Molecular Biology
• Bone Biology

Background:

• Aging is associated with osteoporosis and muscle degeneration.
• The muscle molecular clock's role in age-related bone health is largely unknown.
• Bmal1 disruption in muscle impacts systemic physiology.

Purpose of the Study:

• Investigate the role of the muscle molecular clock, specifically Bmal1, in age-related osteoporosis.
• Elucidate the mechanisms linking muscle Bmal1 to bone metabolism.
• Evaluate time-restricted feeding (TRF) as a potential therapeutic intervention.

Main Methods:

• Utilized aged mice and skeletal muscle-specific Bmal1 knockout mice.
• Analyzed bone mass, microarchitecture, and inflammatory cytokine expression.
• Assessed the impact of nighttime TRF on molecular clock function and bone phenotypes.

Main Results:

• Aged mice exhibited disrupted muscle-bone circadian interaction and reduced muscle Bmal1.
• Muscle-specific Bmal1 knockout mice displayed osteoporosis phenotypes and altered cytokine rhythms.
• Muscle Bmal1 deficiency upregulated IL-1α, promoting osteoclast differentiation and bone loss.
• Nighttime TRF alleviated osteoporosis phenotypes by restoring muscle Hmox1 rhythm and reducing serum IL-1α.

Conclusions:

• Muscle Bmal1 plays a critical role in maintaining bone health during aging.
• Muscle Bmal1 deficiency exacerbates osteoporosis via IL-1α signaling.
• Nighttime TRF is a promising strategy to combat age-related osteoporosis by targeting the muscle clock.