{
  "abstract": "Background: Sarcopenia is a progressive muscle-wasting condition driven in part by chronic inflammation; however, the specific inflammatory mediators that contribute to functional decline in humans and their responses to exercise remain poorly defined.\n\nMethods: We analyzed public ribonucleic acid (RNA) datasets to identify inflammatory pathways associated with aging and exercise. Additionally, we validated candidate factors in older adults through 2 human studies. Complementary cellular and animal experiments were performed to dissect the mechanistic responses to muscle atrophy, injury, and exercise-mimetic therapies.\n\nResults: C-X-C motif chemokine ligand 2 (CXCL2) was identified as a prominent age-associated exercise-responsive inflammatory factor in human datasets. In older adults, plasma CXCL2 levels increased with sarcopenia severity and correlated with Sarcopenia Probability Score (SPS)-defined functional impairment (r = 0.6472, p = 0.0003). In the 48-week human intervention, structured exercise substantially improved strength, mobility, and endurance and markedly reduced circulating CXCL2 (p < 0.0001) and tumor necrosis factor-alpha (TNF-α) levels (p < 0.0001). In contrast, individuals in the non-exercise group exhibited progressive functional decline and increased cytokine levels. Moreover, Cxcl2 expression was upregulated in the skeletal muscles of aged mice and induced by muscle atrophy or injury (p = 0.0082). In contrast, exercise-mimetic stimulation and acute endurance exercise suppressed Cxcl2 expression (p = 0.0148 and p = 0.0072, respectively). Importantly, blocking CXCL2–C-X-C motif chemokine receptor 2 (CXCR2) signaling attenuated dexamethasone-induced expression of the atrophy markers Fbxo32 (p = 0.0336, 0.0127, 0.0061) and Trim63 (p = 0.0296, 00160, 0.0042).\n\nConclusion: Human evidence from year-long clinical exercise interventions, supported by transcriptomic, cellular, and animal experiments, identified CXCL2 as a modifiable inflammatory mediator linking aging to muscle atrophy. Consistent suppression of CXCL2 by exercise and attenuation of atrophic signaling through CXCR2 inhibition highlight the CXCL2–CXCR2 axis as a promising target for mitigating sarcopenia.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Molecular Biology, Pusan National University, Busan 46241, Republic of Korea",
    "Department of Sport Science, School of Sport Science, Pusan National University, Busan 46241, Republic of Korea",
    "Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea",
    "Brain Science and Engineering Institute, Kyungpook National University, Daegu 41404, Republic of Korea",
    "Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea",
    "Institute of Systems Biology, Pusan National University, Busan 46241, Republic of Korea"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Juyeon Lee"
    },
    {
      "affs": [
        1
      ],
      "name": "Sung-Wook Chun"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Subin Choi"
    },
    {
      "affs": [
        4
      ],
      "name": "Jae Sook Kang"
    },
    {
      "affs": [
        4
      ],
      "name": "Seong Jun Park"
    },
    {
      "affs": [
        4
      ],
      "name": "Yong Ryoul Yang"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Hwa-Rim Lee"
    },
    {
      "affs": [
        0,
        5
      ],
      "name": "Kyung-Ha Lee"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ehhx02akz19pj.bib",
  "cited_by": 0,
  "doi": "10.1016/j.jshs.2026.101159",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13738289/",
  "id": "ehhx02akz19pj",
  "issns": [
    "2095-2546",
    "2213-2961"
  ],
  "landing_url": "https://doi.org/10.1016/j.jshs.2026.101159",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Article"
    ],
    [
      "openalex",
      "2737|Nutrition and Health in Aging"
    ]
  ],
  "openalex": "W7170036292",
  "pdf_url": "https://www.sciencedirect.com/science/article/pii/S2095254626000505/pdf",
  "pmcid": "PMC13738289",
  "pmid": "42486363",
  "published": "2026-07-22",
  "publisher": "Shanghai University of Sport",
  "ris": "https://research.draconitic.com/paper/ehhx02akz19pj.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:23:18Z",
      "native_id": "PMC13738289",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.jshs.2026.101159"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Nutrition and Health in Aging",
      "subfield": "physiology"
    }
  ],
  "title": "CXCL2 is a modifiable driver of sarcopenic inflammation attenuated by exercise in older women: Integrated transcriptomic and experimental evidence",
  "title_text": "CXCL2 is a modifiable driver of sarcopenic inflammation attenuated by exercise in older women: Integrated transcriptomic and experimental evidence",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:23:18Z",
  "url": "https://research.draconitic.com/paper/ehhx02akz19pj",
  "venue": "Journal of Sport and Health Science",
  "versions": []
}