Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
The causal association between circulating cytokines with the risk of frailty and sarcopenia under the perspective of geroscience
Ist Teil von
Frontiers in endocrinology (Lausanne), 2024, Vol.15, p.1293146-1293146
Ort / Verlag
Switzerland: Frontiers Media S.A
Erscheinungsjahr
2024
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
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,
= 0.028, false discovery rate (FDR)-adjusted
= 1.000; OR = 1.03, 95% CI = 1.00-1.07,
= 0.042, FDR-adjusted
= 0.784; OR = 1.02, 95% CI = 1.00-1.05,
= 0.038, FDR-adjusted
= 0.567]. Furthermore, genetically determined higher macrophage colony-stimulating factors (M-CSFs) were associated with a lower presence of appendicular lean mass (OR = 1.01, 95% CI = 1.00-1.02,
= 0.003, FDR-adjusted
= 0.103). Monokine induced by interferon-γ (MIG) and tumor necrosis factor-beta (TNF-β) were associated with a higher risk of frailty (OR = 1.03, 95% CI = 1.01-1.05,
< 0.0001, FDR-adjusted
= 0.012; OR = 1.01, 95% CI = 1.00-1.03,
= 0.013, FDR-adjusted
= 0.259). In this study, we did not find heterogeneity and horizontal pleiotropy between the circulating cytokines and the risk of frailty and sarcopenia.
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.