Kunihiro Sakuma and his colleagues in cooperation with researchers at Kyoto Prefectural University and the Heath Science University of Hokkaido, have detected marked upregulation of p62/SQSTM1, but not LC3, protein levels in the cytosol of sarcopenic muscle fibers in mice. This unbalanced expression appears to induce an autophagic defect in skeletal muscle and consequent loss of muscle mass. This finding contributes to our understanding of the molecular mechanism of sarcopenia, or muscle aging.
Sarcopenia is the aging-related loss of skeletal muscle mass and strength. Preventing sarcopenia is important for maintaining a high quality of life (QOL) in the aged population. However, the molecular mechanism of sarcopenia has not yet been unraveled and is still a matter of debate. Determining whether the levels of autophagy-related mediators (e.g., p62/SQSTM1, LC3, etc.) in muscle change with ageing is important to understanding sarcopenia. Such information could enhance the therapeutic strategies for attenuating mammalian sarcopenia.
In previous studies, autophagic defects were detected in the sarcopenic muscle of mice, rats, and humans. However, all these studies involved only western blotting analyses of crude not cell-fractionated muscle homogenates. Thus, these data were insufficient to describe the adaptive changes in autophagy-linked molecules within sarcopenic muscle.
Associate Professor Kunihiro Sakuma and his colleagues at Toyohashi Tech found a marked accumulation of p62/SQSTM1 in the sarcopenic quadriceps muscle of mice using two different methods (western blotting of cell-fractionated homogenates and immunofluorescence). In contrast, the expression level of LC3, a partner of p62/SQSTM1 in autophagy progression, was not modulated.
The detected autophagic defect improves our understanding of the mechanism underlying sarcopenia. The researchers would like to further study this mechanism with an aim to attenuate sarcopenia by ameliorating this autophagic defect using nutrient- and pharmaceutical-based treatments.
Sakuma, K., Kinoshita, M., Ito, Y., Aizawa, M., Aoi, W., and Yamaguchi, A. (2015). p62/SQSTM1 but not LC3 is accumulated in sarcopenic muscle of mice, Journal of Cachexia, Sarcopenia, and Muscle, DOI: 10.1002/jcsm.12045 (Published online before print)
|Affiliation||Institute of Liberal Arts and Science|
|Fields of Research||Exercise Biochemistry /Exercise Physiology|