"Exercise is good for your health" is a well-known phrase, but few people can clearly explain how and why it benefits the human body."
A joint research team, led by Dr. Yong Ryoul Yang of the Aging Convergence Research Group at the Korea Research Institute of Bioscience and Biotechnology (KRIBB, President: Seok-Yoon Kwon) and Professor Nak-Sung Kim of Chonnam National University, has discovered a key protein, CLCF1 (cardiotrophin-like cytokine factor 1), that plays a central role in mediating the health benefits of physical activity.
The team found that CLCF1 is secreted by muscles during exercise, where it helps strengthen both muscles and bones, thereby suppressing musculoskeletal aging.
To understand how CLCF1 changes in response to exercise and aging, the researchers divided participants into young and elderly groups and monitored changes in blood CLCF1 levels after exercise. Interestingly, CLCF1 levels increased markedly after a single exercise session in the younger group, whereas in older adults, the protein only increased after over 12 weeks of continuous exercise.
The team also conducted experiments on aged mice. When CLCF1 was administered to elderly mice, they showed improved muscle strength and increased bone density. In contrast, blocking the action of CLCF1 made exercise ineffective, confirming that this protein is essential for the beneficial effects of exercise.
Further analysis showed that CLCF1 enhances mitochondrial function in muscle cells, inhibits the formation of bone-resorbing osteoclasts, and promotes the differentiation of bone-forming osteoblasts. This is the first scientific evidence identifying changes in protein secretion as a major reason for the reduced efficacy of exercise in aging individuals.
This research provides a biological basis for why exercise becomes less effective with age, and it lays the groundwork for developing new therapeutic strategies for healthy aging. In particular, the findings offer new directions for treating age-related sarcopenia and osteoporosis."
Dr. Yong Ryoul Yang from KRIBB
Korea Research Institute of Bioscience and Biotechnology (KRIBB) is a leading national research institute in South Korea dedicated to cutting-edge research in biotechnology and life sciences. Established in 1985, KRIBB focuses on advancing scientific knowledge in areas such as molecular biology, genomics, bioinformatics, synthetic biology, and aging-related studies. As a government-funded institute, KRIBB plays a pivotal role in driving innovation, supporting national R&D strategies, and collaborating with academic and industrial partners both domestically and internationally.
This research was supported by the National Research Foundation of Korea (NRF) Individual Basic Science Program, the Regional Science & Technology Innovation Project, the Convergence Research Program of NST, and KRIBB's core R&D program.
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Journal reference:
Kang, J. S., et al. (2025). Exercise-induced CLCF1 attenuates age-related muscle and bone decline in mice. Nature Communications. doi.org/10.1038/s41467-025-59959-w.