The connection between 91 inflammatory cytokines and frailty mediated by 1400 metabolites: An exploratory two-step Mendelian randomization analysis

作者：Bo Wen, Shizhuang Wei, Daolai Huang, Chao Zhang, Hua Wang, Sisi Liu, Xianghua Wu · 发表于：Archives of Gerontology and Geriatrics · 年份：2025 · DOI：10.1016/j.archger.2025.105774 · 被引用次数：4 · 研究领域：Frailty in Older Adults、GDF15 and Related Biomarkers、Ferroptosis and cancer prognosis

• What is already known on this topic The increasing evidence indicates that inflammatory cytokines are implicated in the pathogenesis of frailty. Nevertheless, the causal relationship remains indistinct. • What this study adds In this study, Mendelian randomization analysis was performed for regarding the causality between 8 inflammatory cytokines and frailty. Moreover, we identified 2 mediated relationships, with 2 metabolites acting as potential mediators. • How this study might affect research, practice, or policy This research offers novel perspectives for the prevention and management strategies of frailty. Frailty, a common, multifaceted, and significant geriatric condition, involves crucial roles of inflammation and metabolic factors in its onset and progression. Nevertheless, the ambiguities and complexities in earlier observational studies make current research into their interactions somewhat insufficient. Our goals were to clarify the causal link between inflammatory cytokines and frailty and to explore the potential mediating effect of metabolites using Mendelian randomization (MR) analysis. Utilizing detailed summary-level data from genome-wide association studies, we conducted two-sample Mendelian randomization analyses to evaluate the potential causal connection between 91 inflammatory cytokines and the frailty index, along with the possible mediating pathways that involve 1400 metabolites. For our main analysis, we applied the inverse variance weighted method...