Exercise-induced CLCF1 attenuates age-related muscle and bone decline in mice
Abstract Skeletal muscle undergoes many alterations with aging. However, the impact of aging on muscle’s ability to secrete myokines and its subsequent effects on the body remain largely unexplored. Here, we identify myokines that have the potential to ameliorate age-related muscle and bone decline....
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Nature Portfolio
2025-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59959-w |
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| author | Jae Sook Kang Jung Ha Kim Min Ju Kim Byungkuk Min Seung-Min Lee Ga-Yeon Go Ji-Won Kim Seongwan Kim Ju Yeon Kwak Sung-Wook Chun Wook Song Hyo Youl Moon Sun Gun Chung Dong-Ho Park Ji Hoon Park Chuna Kim Kwang-Pyo Lee Eun-Soo Kwon Nacksung Kim Ki-Sun Kwon Yong Ryoul Yang |
| author_facet | Jae Sook Kang Jung Ha Kim Min Ju Kim Byungkuk Min Seung-Min Lee Ga-Yeon Go Ji-Won Kim Seongwan Kim Ju Yeon Kwak Sung-Wook Chun Wook Song Hyo Youl Moon Sun Gun Chung Dong-Ho Park Ji Hoon Park Chuna Kim Kwang-Pyo Lee Eun-Soo Kwon Nacksung Kim Ki-Sun Kwon Yong Ryoul Yang |
| author_sort | Jae Sook Kang |
| collection | DOAJ |
| description | Abstract Skeletal muscle undergoes many alterations with aging. However, the impact of aging on muscle’s ability to secrete myokines and its subsequent effects on the body remain largely unexplored. Here, we identify myokines that have the potential to ameliorate age-related muscle and bone decline. Notably, circulating levels of cardiotrophin-like cytokine factor 1 (CLCF1) decrease with age, while exercise significantly upregulates CLCF1 levels in both humans and rodents. Restoring CLCF1 levels in aged male mice improves their physical performance, glucose tolerance, and mitochondrial activity. Furthermore, CLCF1 protects against age-induced bone loss by inhibiting osteoclastogenesis and promoting osteoblast differentiation in aged male mice. These improvements mirror some of the effects of exercise training. Conversely, blocking CLCF1 activity significantly abolishes these beneficial effects, confirming the crucial role of CLCF1 in mediating the positive effects of exercise on muscle and bone health in male mice. These findings collectively suggest that CLCF1 may contribute to the regulation of age-associated musculoskeletal deterioration, and warrant further investigation into its potential role as a modulator of musculoskeletal health during aging. |
| format | Article |
| id | doaj-art-4e6fa0ce97d743efa1d0e7e1f3cc7933 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-4e6fa0ce97d743efa1d0e7e1f3cc79332025-08-20T01:53:23ZengNature PortfolioNature Communications2041-17232025-05-0116112010.1038/s41467-025-59959-wExercise-induced CLCF1 attenuates age-related muscle and bone decline in miceJae Sook Kang0Jung Ha Kim1Min Ju Kim2Byungkuk Min3Seung-Min Lee4Ga-Yeon Go5Ji-Won Kim6Seongwan Kim7Ju Yeon Kwak8Sung-Wook Chun9Wook Song10Hyo Youl Moon11Sun Gun Chung12Dong-Ho Park13Ji Hoon Park14Chuna Kim15Kwang-Pyo Lee16Eun-Soo Kwon17Nacksung Kim18Ki-Sun Kwon19Yong Ryoul Yang20Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Department of Pharmacology, Chonnam National University Medical SchoolAging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Stem Cell Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Research Institute of Physical Education & Sports Science, Pusan National UniversityDepartment of Physical Education, Seoul National UniversityDepartment of Physical Education, Seoul National UniversityInstitute on Aging, Seoul National UniversityDepartment of Kinesiology, Inha UniversityNew Drug Development Center, Osong Medical Innovation Foundation (KBioHealth)Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Department of Pharmacology, Chonnam National University Medical SchoolAging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Abstract Skeletal muscle undergoes many alterations with aging. However, the impact of aging on muscle’s ability to secrete myokines and its subsequent effects on the body remain largely unexplored. Here, we identify myokines that have the potential to ameliorate age-related muscle and bone decline. Notably, circulating levels of cardiotrophin-like cytokine factor 1 (CLCF1) decrease with age, while exercise significantly upregulates CLCF1 levels in both humans and rodents. Restoring CLCF1 levels in aged male mice improves their physical performance, glucose tolerance, and mitochondrial activity. Furthermore, CLCF1 protects against age-induced bone loss by inhibiting osteoclastogenesis and promoting osteoblast differentiation in aged male mice. These improvements mirror some of the effects of exercise training. Conversely, blocking CLCF1 activity significantly abolishes these beneficial effects, confirming the crucial role of CLCF1 in mediating the positive effects of exercise on muscle and bone health in male mice. These findings collectively suggest that CLCF1 may contribute to the regulation of age-associated musculoskeletal deterioration, and warrant further investigation into its potential role as a modulator of musculoskeletal health during aging.https://doi.org/10.1038/s41467-025-59959-w |
| spellingShingle | Jae Sook Kang Jung Ha Kim Min Ju Kim Byungkuk Min Seung-Min Lee Ga-Yeon Go Ji-Won Kim Seongwan Kim Ju Yeon Kwak Sung-Wook Chun Wook Song Hyo Youl Moon Sun Gun Chung Dong-Ho Park Ji Hoon Park Chuna Kim Kwang-Pyo Lee Eun-Soo Kwon Nacksung Kim Ki-Sun Kwon Yong Ryoul Yang Exercise-induced CLCF1 attenuates age-related muscle and bone decline in mice Nature Communications |
| title | Exercise-induced CLCF1 attenuates age-related muscle and bone decline in mice |
| title_full | Exercise-induced CLCF1 attenuates age-related muscle and bone decline in mice |
| title_fullStr | Exercise-induced CLCF1 attenuates age-related muscle and bone decline in mice |
| title_full_unstemmed | Exercise-induced CLCF1 attenuates age-related muscle and bone decline in mice |
| title_short | Exercise-induced CLCF1 attenuates age-related muscle and bone decline in mice |
| title_sort | exercise induced clcf1 attenuates age related muscle and bone decline in mice |
| url | https://doi.org/10.1038/s41467-025-59959-w |
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