Yuan-Yuei Chen,1– 3 Tung-Wei Kao,3 Yi-Lin Chiu,4 Tao-Chun Peng,3 Hui-Fang Yang,3 Wei-Liang Chen3,4 1Department of Pathology, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China; 2Department of Pathology, Tri-Service General Hospital Songshan Branch, School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China; 3Division of Geriatric Medicine, Department of Family and Community Medicine, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China; 4Department of Biochemistry, National Defense Medical Center, Taiwan, Republic of ChinaCorrespondence: Wei-Liang ChenDivision of Geriatric Medicine, Department of Family Medicine, Tri-Service General Hospital, National Defense Medical Center, Number 325, Section 2, Chang-Gong Road, Nei-Hu District, Taipei, 114, TaiwanTel +886-2-87923311 ext. 16567Fax +886-2-87927057Email weiliang0508@gmail.comBackground: Emerging studies have proposed that cytokines secreted following macrophage polarization may contribute to skeletal muscle aging. The current study primarily aimed to determine whether these cytokines have an impact on the progression of sarcopenia in an elderly population.Methods: In total, 120 elderly adults aged 65 years and older who underwent health examinations from 2015 to 2019 were included in this retrospective study. Sarcopenia was based on the criteria proposed by the European Working Group on Sarcopenia in Older People in 2019. Macrophages and cytokines datasets were obtained from Gene Expression Omnibus (GEO) database. Comprehensive assessments were performed for muscle strength, muscle mass, gait speed, tumor growth factor-β (TGF-β), and interleukin-12 (IL-12). Thereafter, the association between sarcopenia and cytokines was analyzed using regression models.Results: Low muscle strength and low-speed gait were negatively associated with IL-12 [β: − 8.96 (95% CI: − 14.12, − 3.79) and − 7.16 (95% CI: − 12.54, − 1.78), respectively]. Participants with more sarcopenia components and more severe sarcopenia had lower IL-12 (P for trend < 0.001). Conversely, more amount of sarcopenia components were associated with increased TGF-β (P for trend < 0.05). A definite diagnosis of sarcopenia was associated with decreased IL-12 and increased TGF-β with β of − 8.96 (95% CI: − 14.12, − 3.79) and 147.75 (95% CI: 36.27, 259.23). Furthermore, increased IL-12 levels were significantly associated with reduced occurrence of sarcopenia with and odd ratio (OR) of 0.36 (95% CI: 0.15– 0.834).Conclusion: Our findings on the relationship between cytokines and age-related muscle loss showed that IL-12 may be an early diagnosis indicator for sarcopenia in the elderly population.Keywords: gender, sarcopenia, IL-12, TGF-β, macrophage