✍Research Review: Skeletal muscle gene expression dysregulation in long-term spaceflights and aging

🌐Link to the paper: https://www.nature.com/articles/s41526-023-00273-4...

The paper investigates the potential functional consequences of circadian clock disruptions in skeletal muscle due to intrinsic and extrinsic factors, such as aging and spaceflight. The study identifies alterations of the clock network and skeletal muscle-associated pathways, emphasizing the importance of maintaining circadian functioning to ameliorate unphysiological alterations and musculoskeletal atrophy reported among astronauts.

The paper also characterizes the circadian phenotype within the skeletal muscle of healthy mammalian tissues and investigates the impact of core-clock specific alterations on skeletal muscle phenotype.

The paper has practical implications for maintaining the health of astronauts during long-term spaceflights. The study emphasizes the importance of maintaining circadian functioning to ameliorate unphysiological alterations and musculoskeletal atrophy reported among astronauts. The findings suggest that external factors such as exercise or fasting may compensate for the circadian disruption observed during spaceflights. The study also highlights the potential implications of spaceflights in neurodegeneration, which may require further research in this direction. However, the practical implications of this paper are limited to the domain of spaceflight and circadian biology and do not extend to other fields.

The introduction of the paper highlights the importance of skeletal muscle, one of the most dynamic and plastic organs of the human body, which is regulated by the dynamic control of protein synthesis and degradation that are sensitive to factors such as nutritional status and physical activity. Aging results in a gradual loss of muscle function, which varies based on sex and the level of muscle activity.

The accelerated loss of muscle mass and function, associated with increased adverse outcomes including falls and frailty, results in sarcopenia (also called muscle wasting). The introduction also emphasizes the importance of the circadian clock in regulating cellular and molecular processes in mammals across all tissues, including skeletal muscle, and characterizes the circadian phenotype within the skeletal muscle of healthy mammalian tissues.

The paper provides a literature survey of the existing research on the circadian clock and skeletal muscle. The authors discuss the role of the circadian clock in regulating skeletal muscle function and the impact of circadian disruption on skeletal muscle-associated pathways. They also review the existing literature on the effects of aging, exercise, and fasting on skeletal muscle and the circadian clock. The authors highlight the need for further research to understand the molecular mechanisms underlying the relationship between the circadian clock and skeletal muscle and to develop interventions to maintain skeletal muscle function in aging and spaceflight.

The paper used a systematic analysis to investigate the potential functional consequences of circadian clock disruptions in skeletal muscle due to intrinsic and extrinsic factors. The authors used datasets from 28 published genomics (microarray, RNA-seq) and proteomics (LC-MS) based studies to identify alterations in the clock network and skeletal muscle-associated pathways resulting from spaceflight duration in mice, which resembles aging-related gene expression changes observed in humans on Earth. The authors also investigated the impact of core-clock specific alterations (Bmal1 knockout or Clock mutant or CLOCK knockdown vs. WT) on skeletal muscle phenotype. The datasets used in this study were obtained from skeletal muscle tissue or cells, and the LC-MS datasets were derived from the mouse model system.

The paper investigated potential functional consequences of clock disruptions on skeletal muscle using published omics datasets obtained from spaceflights and other clock-altering, external (fasting and exercise), or internal (aging) conditions on Earth. The analysis identified alterations of the clock network and skeletal muscle-associated pathways, as a result of spaceflight duration in mice, which resembles aging-related gene expression changes observed in humans on Earth. Furthermore, external factors such as exercise or fasting lead to molecular changes in the core-clock network, which may compensate for the circadian disruption observed during spaceflights. The study suggests that maintaining circadian functioning is crucial to ameliorate unphysiological alterations and musculoskeletal atrophy reported among astronauts.

Based on the analysis of the omics datasets, the paper concludes that maintaining circadian functioning is crucial to ameliorate unphysiological alterations and musculoskeletal atrophy reported among astronauts. The study also suggests that external factors such as exercise or fasting lead to molecular changes in the core-clock network, which may compensate for the circadian disruption observed during spaceflights. The paper highlights the importance of understanding the molecular mechanisms underlying circadian regulation in skeletal muscle and its potential implications for spaceflight and aging.

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