The existence of muscle that does not deteriorate when not in use! Discovery during research on Asiatic black bears which enter an "energy-saving mode" during hibernation

A research group consisting of Associate Professor Mitsunori Miyazaki of the Department of Integrative Physiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Associate Professor Michito Shimozuru and Professor Toshio Tsubota of the Laboratory of Wildlife Biology and Medicine, Graduate School of Veterinary Medicine, Hokkaido University, Associate Professor Yu Kitaoka of the Faculty of Human Sciences, Kanagawa University, Research Associate Kenya Takahashi of the University of Tokyo (UTSSK; Life Sciences, Multidisciplinary Sciences, Graduate School of Arts and Sciences, the University of Tokyo), and their colleagues, has clarified that during hibernation, the skeletal muscles of Asiatic black bears enter an "energy-saving mode" that suppresses the degradation of muscle proteins as nutrients, therefore ensuring "no use, but no loss" of muscle.

The muscles that move the body become stronger and grow (hypertrophy) the more they are used for exercise, training, and similar purposes. On the other hand, if they are continuously inactive due to injury, illness or a reduction in gravitational stress (e.g. being in space or being bedridden), they weaken, become smaller which results in muscle loss. This is known as the "Use it or lose it" phenomenon. The research group believed that, rather than returning weakened muscles to their original state, it was possible to create muscles that do not weaken, and engaged in research on the characteristics of the "no use no loss" bodies of hibernating animals.

First, muscle samples were taken from eight hibernating Asiatic black bears and analyzed and compared with samples from when the same individuals were active. The results confirmed that there was no change in the size of the skeletal muscle fibers or the proportion of slow muscles/slow muscle fibers - in other words, there was no deterioration at all during hibernation. Next, the group measured the activation state of the Akt/mTOR network and MEK/ERK pathway, which are control systems for the synthesis of muscle proteins. When they did so, they found that these were significantly suppressed in the skeletal muscles during hibernation. Moreover, when they measured the genetic expression of the factors involved in autophagy and Ub-Proteasome system 4, an indicator of the protein degradation control system, it became clear that these are also largely suppressed in the skeletal muscles during hibernation.

In the skeletal muscles of hibernating bears, the command systems that create and degrade proteins were remarkably suppressed. Moreover, the genetic expression and enzyme activity of control factors associated with the mitochondria that control oxidative energy metabolism (producing energy from lipids and sugars while using oxygen) were also significantly suppressed. Comparing this with the bears' period of activity, it became clear that the systems that regulate the protein metabolism and lipid metabolism are both greatly suppressed, and this suggested that going into energy-saving mode during the hibernation period, which entails long-term fasting, prevents the wasted use of energy and is an adaptation strategy for surviving the winter environment.

Miyazaki commented, "We have no idea what mechanism induces this muscle energy-saving mode. We want to clarify this unexplained mechanism that ensures that the muscles of hibernating animals do not deteriorate when they are not used, including the specifics of the factors involved. Ultimately, we hope this will make it possible to prevent people being bedridden and to develop effective rehabilitation techniques."

■ Akt/mTOR: A signaling molecule that controls the activation of proteins associated with protein synthesis (translation) in ribosomes.

■ MEK/ERK network: An information communication network involved in many different cellular processes, including cell proliferation, growth and differentiation, in a variety of cell types.

■ Ub-Proteasome system: A system in which proteosomes recognize ubiquitin chains attached to proteins, which ensures selective, ATP-dependent degradation of target proteins.

■ Autophagy: Literally means "self-devouring." As this process involves the complete digestion of a cytoplasmic space surrounded by an isolation membrane known as an autophagosome, it is also referred to as the bulk degradation of proteins.

Journal Information
Publication: Scientific Reports
Title: Regulation of protein and oxidative energy metabolism are down-regulated in the skeletal muscles of Asiatic black bears during hibernation
DOI: 10.1038/s41598-022-24251-0