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Exercise-induced CLCF1 attenuates age-related muscle and bone decline in mice

Author

Listed:
  • Jae Sook Kang

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB)
    Korea University of Science and Technology (UST))

  • Jung Ha Kim

    (Chonnam National University Medical School)

  • Min Ju Kim

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB)
    Korea University of Science and Technology (UST))

  • Byungkuk Min

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB))

  • Seung-Min Lee

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB))

  • Ga-Yeon Go

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB))

  • Ji-Won Kim

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB))

  • Seongwan Kim

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB)
    Korea University of Science and Technology (UST))

  • Ju Yeon Kwak

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB))

  • Sung-Wook Chun

    (Pusan National University)

  • Wook Song

    (Seoul National University
    Seoul National University)

  • Hyo Youl Moon

    (Seoul National University
    Seoul National University)

  • Sun Gun Chung

    (Seoul National University
    Seoul National University College of Medicine)

  • Dong-Ho Park

    (Inha University
    Inha University)

  • Ji Hoon Park

    (Osong Medical Innovation Foundation (KBioHealth))

  • Chuna Kim

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB)
    Korea University of Science and Technology (UST))

  • Kwang-Pyo Lee

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB)
    Korea University of Science and Technology (UST))

  • Eun-Soo Kwon

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB)
    Korea University of Science and Technology (UST))

  • Nacksung Kim

    (Chonnam National University Medical School)

  • Ki-Sun Kwon

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB)
    Aventi Inc.)

  • Yong Ryoul Yang

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB)
    Korea University of Science and Technology (UST))

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.

Suggested Citation

  • 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 P, 2025. "Exercise-induced CLCF1 attenuates age-related muscle and bone decline in mice," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59959-w
    DOI: 10.1038/s41467-025-59959-w
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    References listed on IDEAS

    as
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