CXCL2 is a modifiable driver of sarcopenic inflammation attenuated by exercise in older women: Integrated transcriptomic and experimental evidence
6 affiliations
- 1Department of Molecular Biology, Pusan National University, Busan 46241, Republic of Korea
- 2Department of Sport Science, School of Sport Science, Pusan National University, Busan 46241, Republic of Korea
- 3Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea
- 4Brain Science and Engineering Institute, Kyungpook National University, Daegu 41404, Republic of Korea
- 5Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea
- 6Institute of Systems Biology, Pusan National University, Busan 46241, Republic of Korea
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.
Methods: 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.
Results: 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).
Conclusion: 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.
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BibTeX
@article{lee2026cxcl2,
title = {{CXCL2 is a modifiable driver of sarcopenic inflammation attenuated by exercise in older women: Integrated transcriptomic and experimental evidence}},
author = {Juyeon Lee and Sung-Wook Chun and Subin Choi and Jae Sook Kang and Seong Jun Park and Yong Ryoul Yang and Hwa-Rim Lee and Kyung-Ha Lee},
journal = {Journal of Sport and Health Science},
year = {2026},
month = jul,
doi = {10.1016/j.jshs.2026.101159},
url = {https://doi.org/10.1016/j.jshs.2026.101159},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - CXCL2 is a modifiable driver of sarcopenic inflammation attenuated by exercise in older women: Integrated transcriptomic and experimental evidence
AU - Juyeon Lee
AU - Sung-Wook Chun
AU - Subin Choi
AU - Jae Sook Kang
AU - Seong Jun Park
AU - Yong Ryoul Yang
AU - Hwa-Rim Lee
AU - Kyung-Ha Lee
PY - 2026
DA - 2026/07/22
JO - Journal of Sport and Health Science
DO - 10.1016/j.jshs.2026.101159
UR - https://doi.org/10.1016/j.jshs.2026.101159
AB - 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. Methods: 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. Results: 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). Conclusion: 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.
SN - 2095-2546
SN - 2213-2961
ER -