The adage “Exercise is good for your health” is widely accepted, yet few people can explain with precision the biological mechanisms that underpin this truth. A groundbreaking discovery by a joint research team sheds new light on this topic, identifying a key protein that mediates the health benefits of physical activity. The study was led by Dr Yong Ryoul Yang of the Aging Convergence Research Group at the Korea Research Institute of Bioscience and Biotechnology (KRIBB), alongside Professor Nak-Sung Kim of Chonnam National University. Together, they identified cardiotrophin-like cytokine factor 1 (CLCF1), a protein secreted by muscles during exercise, as a crucial player in enhancing both muscular and skeletal health.
The research demonstrated that CLCF1 contributes to the prevention of musculoskeletal ageing by strengthening muscles and bones. In human trials, the team observed that CLCF1 levels rose sharply after just one exercise session in young participants. However, in older adults, the same increase in CLCF1 was only seen after more than 12 weeks of sustained exercise. This finding indicates a significant age-related difference in how the body produces and responds to this protein, potentially explaining why older individuals often require more extended periods of activity to experience the same benefits as their younger counterparts.
To better understand the physiological role of CLCF1, the team conducted a series of experiments on elderly mice. Administering CLCF1 to these mice resulted in marked improvements in muscle strength and bone density. Conversely, when CLCF1 activity was blocked, the beneficial effects of exercise were entirely nullified. These results confirmed that CLCF1 is not merely a byproduct of exercise but a necessary component of its positive impact. In essence, the presence and activity of this protein determine whether the body reaps the regenerative rewards of physical training.
Further cellular analysis revealed the mechanisms behind CLCF1’s efficacy. The protein enhances mitochondrial function in muscle cells, thereby improving energy production and cellular endurance. It also inhibits the formation of osteoclasts—cells that break down bone tissue—while promoting the activity of osteoblasts, which are responsible for bone formation and repair. This dual action supports not only muscle vitality but also bone density, making CLCF1 a key agent in the fight against age-related conditions such as sarcopenia and osteoporosis.
Dr Yang emphasised the significance of the discovery, noting that this is the first scientific evidence linking diminished protein secretion with the reduced effectiveness of exercise in older individuals. “This research provides a biological basis for why exercise becomes less effective with age,” he explained. “It also lays the groundwork for developing new therapeutic strategies for healthy ageing.” The study’s insights could lead to treatments that mimic or enhance the action of CLCF1, offering hope to those unable to maintain regular exercise due to ageing or illness, and opening a new frontier in the science of longevity and musculoskeletal health.
More information: Yong Ryoul Yang et al, Exercise-induced CLCF1 attenuates age-related muscle and bone decline in mice, Nature Communications. DOI: 10.1038/s41467-025-59959-w
Journal information: Nature Communications Provided by National Research Council of Science & Technology
