Researchers from the University of Tsukuba have found a new gene involved in muscle atrophy when they sent mice into space to explore effects of weightlessness on skeletal muscles.
Extended periods of skeletal muscle inactivity or mechanical unloading (bed rest, immobilisation, spaceflight and reduced step) can result in a significant loss of muscle mass and strength which ultimately lead to muscle atrophy. Spaceflight is one of the leading models of understanding muscle atrophy from disuse.
As the molecular and cellular mechanisms involved in disuse skeletal muscle atrophy have been studied, several different signaling pathways have been studied to understand their regulatory role in this process. However, large gaps exist in the understanding of the regulatory mechanisms involved, as well as their functional significance.
Prior studies examining the effects of reduced gravity on muscle mass and function have used a ground control group which cannot be directly compared to the space experimental group. Researchers from the University of Tsukuba set out to explore the effects of gravity in mice subjected to the same housing conditions, such as the stresses of launch, landing and cosmic radiation. “In humans, spaceflight causes muscle atrophy and can lead to serious medical problems after return to Earth” says senior author Professor Satoru Takahashi. “This study was designed based on the critical need to understand the molecular mechanisms through which muscle atrophy occurs in conditions of microgravity and artificial gravity.”
Two groups of six mice each were housed onboard the International Space Station for 35 days. One group was subjected to artificial gravity (1g) and the other was left in microgravity. All mice were returned to Earth aboard a Dragon capsule and the team compared the effects of the different onboard environments on skeletal muscles. “To understand what was happening inside the muscles and cells, at the molecular level, we examined the muscle fibers. Our results show that artificial gravity prevents the changes observed in mice subjected to microgravity, including muscle atrophy and changes in gene expression,” explained Prof Takahashi.
Transcriptional analysis of gene expression showed that the artificial gravity environment prevented altered expression of atrophy-related genes, and also identified other genes possibly associated with atrophy. Specifically, a gene called Cacng1 was identified as possibly having a functional role in myotube atrophy, which previously had no known function, and was shown to have increased activity when muscle atrophy was present.
When muscle fibres were cultured in vitro, ones which had Cacng1 expression upregulated were decreased in diameter by 27.5%. A similar effect was seen in newborn mice with upregulated Cacng1.
This work validated the use of 1g artificial gravity environments in spaceflight for examining the effects of microgravity in muscles. These studies add to the body of knowledge surrounding the mechanisms of muscle atrophy, possibly improving the treatment of related diseases.
Source: Tsukuba University
Journal information: Okada, R., et al. (2021) Transcriptome analysis of gravitational effects on mouse skeletal muscles under microgravity and artificial 1 g onboard environment. Scientific Reports. doi.org/10.1038/s41598-021-88392-4.
