Hibernating hamsters maintain muscle cells by suppressing muscle regeneration

Skeletal muscle stem cells in hibernating Syrian hamsters preserve their ability to function by suppressing their activation during the hibernation period, a research team led by Hiroshima University has shown. This insight may lead to a broader understanding of the maintenance of muscle tissue under prolonged low temperature conditions and may eventually lead to therapeutic applications.  

Hibernating animals are known to maintain their muscle mass during periods of hibernation, despite the lack of food during these periods. Typically, skeletal muscle undergoes severe atrophy and impaired regeneration during prolonged inactivity or low temperature. 

A team of researchers led by Hiroshima University, and including Fukuyama University, Hokkaido University and Kitasato University, have gained insights into how Syrian hamsters preserve muscle mass during hibernation. They discovered that skeletal muscle stem cells, better known as satellite cells (SCs), have altered gene expression during hibernation, which leads to the maintenance of their viability at the cost of suppressing the generation and regeneration of muscle tissue.  

Their findings were published in The FASEB Journal on December 1, 2025. 

“The primary question of this study was how skeletal muscle stem cells (satellite cells), which are essential for muscle regeneration, adapt to such harsh conditions during hibernation,” says Mitsunori Miyazaki, associate professor at the Graduate School of Biomedical and Health Sciences, Hiroshima University. “Understanding this mechanism is important because muscle loss due to aging, prolonged bed rest, or disease is a major clinical problem in humans, and hibernating animals represent a unique natural model of muscle preservation.” 

The research team isolated SCs from Syrian hamsters, chipmunks and black bears (hibernating species); and rats and mice (non-hibernating species), and established SCs cell cultures for the study. The preliminary step was an analysis of resistance to cold-included cell death (CICD): SCs from non-hibernators were much more susceptible to CICD that those from hibernators and torpor. They also showed that the enzyme glutathione peroxidase 4 (GPX4) — which protects cells from oxidative stress and inhibits a type of programmed cell death called ferroptosis — is abundant in Syrian hamster SCs, indicating that CICD in Syrian hamsters is mediated by ferroptosis. 

RNA analysis indicated that genes controlling myogenesis, or muscle formation, in SCs of hibernating Syrian hamsters are downregulated. Genes mediating the activation of SCs and the differentiation of muscle tissue are also downregulated, triggered by cold exposure. 

Experiments investigating muscle regeneration demonstrated that hibernation suppresses regenerative activation of SCs and delays muscle regeneration following injury. The inflammatory response is also weakened and suppressed.  

“The key message is that hibernating animals protect their muscle stem cells by keeping them alive but deliberately suppressing their regenerative activity,” Miyazaki elaborates. “Under cold conditions and during hibernation, satellite cells remain viable but show a marked suppression of activation, differentiation, inflammation, and muscle regeneration. Our findings suggest that hibernating animals enter an energy-saving state in which costly regenerative processes are selectively downregulated, rather than lost due to cellular damage. The survival and regeneration of SCs are uncoupled in hibernating mammals.” 

“An important next step is to understand how skeletal muscle can be maintained without active regeneration during hibernation, and to identify the molecular mechanisms that regulate this state. Our ultimate goal is to realize the concept of ‘muscle that does not deteriorate' in humans,” Miyazaki concludes. “By learning from hibernating animals, we aim to develop new strategies that help preserve muscle quality and function during prolonged inactivity, such as illness-related bed rest, injury-induced immobilization, aging, or long-duration space travel.”

The research team included Tatsuya Miyaji, Ryuichi Kasuya, Guangyuan Li, Shota Kawano & Yuri Watanabe at Hiroshima University; Daisuke Tsukamoto at Kitasato University; Mayuko Monden, Yutaka Tamura & Masatomo Watanabe at Fukuyama University; and Michito Shimozuru, Toshio Tsubota & Yoshifumi Yamaguchi at Hokkaido University.

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This study was supported by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) KAKENHI (25K22761, 24H02013, 23K18432, 23K24697, 23H04940, 23H04939); The Nakatomi Foundation; The Takeda Science Foundation; and The Hiroshima University Fund “Nozomi H Foundation” subsidy for the promotion of cancer treatment research. 

About Hiroshima University
Since its foundation in 1949, Hiroshima University has striven to become one of the most prominent and comprehensive universities in Japan for the promotion and development of scholarship and education. Consisting of 12 schools for undergraduate level and 5 graduate schools, ranging from natural sciences to humanities and social sciences, the university has grown into one of the most distinguished comprehensive research universities in Japan. English website: https://www.hiroshima-u.ac.jp/en