Skeletal muscle gene expression dysregulation in long-term spaceflights and aging is clock-dependent

Area of Science:

• Chronobiology
• Skeletal Muscle Physiology
• Spaceflight Biology

Background:

• The circadian clock governs essential processes in mammalian tissues, including skeletal muscle.
• Disrupted circadian rhythms are linked to aging and spaceflight, contributing to musculoskeletal atrophy.
• Molecular mechanisms of spaceflight-induced circadian alterations in skeletal muscle remain unclear.

Purpose of the Study:

• To investigate the functional consequences of circadian clock disruption in skeletal muscle.
• To compare spaceflight-induced molecular changes with those from aging, fasting, and exercise on Earth.
• To identify potential compensatory mechanisms for circadian disruption during spaceflight.

Main Methods:

• Analysis of published omics datasets from spaceflight missions.
• Comparison with omics data from Earth-based studies involving aging, fasting, and exercise.
• Investigated alterations in the core clock network and skeletal muscle-associated pathways.

Main Results:

• Spaceflight duration in mice induced alterations in the skeletal muscle clock network and related pathways.
• These spaceflight-induced changes resemble aging-related gene expression patterns observed in humans, including ATF4 downregulation.
• External factors like exercise and fasting induced molecular changes in the core clock network, potentially counteracting spaceflight-induced disruptions.

Conclusions:

• Circadian clock disruption during spaceflight affects skeletal muscle molecular pathways.
• Spaceflight-induced changes in skeletal muscle are comparable to aging processes.
• Maintaining circadian function through factors like exercise is crucial for mitigating muscle atrophy in astronauts.