The causal association between circulating cytokines with the risk of frailty and sarcopenia under the perspective of geroscience.

Circulating cytokines were considered to play a critical role in the initiation and propagation of sarcopenia and frailty from observational studies. This study aimed to find the casual association between circulating cytokines and sarcopenia and frailty from a genetic perspective by two-sample Mendelian randomization (MR) analysis. Data for 41 circulating cytokines were extracted from the genome-wide association study dataset of 8,293 European participants. Inverse-variance weighted (IVW) method, MR-Egger, and weighted median method were applied to assess the relationship of circulating cytokines with the risk of aging-related syndromes and frailty. Furthermore, MR-Egger regression was used to indicate the directional pleiotropy, and Cochran's Q test was used to verify the potential heterogeneity. The "leave-one-out" method was applied to visualize whether there was a causal relationship affected by only one anomalous single-nucleotide polymorphisms. Genetic predisposition to increasing levels of interleukin-10 (IL-10), IL-12, and vascular endothelial growth factor (VEGF) was associated with the higher risk of low hand grip strength according to the IVW method [R = 1.05, 95% CI = 1.01-1.10, Genetic predisposition to assess IL-10, IL-12, and VEGF levels was associated with a higher risk of low hand grip strength and M-CSF with the presence of appendicular lean mass. The high levels of TNF-β and MIG were associated with a higher risk of frailty. More studies will be required to explore the molecular biological mechanisms underlying the action of inflammatory factors.

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Copyright © 2024 Wang, Wang, Wan, Kurihara and Wang.

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The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.