Inflammatory Cytokines and Sarcopenia: Evidence from Mendelian Randomization and Meta-analysis

Several observational studies have found an association between inflammation and sarcopenia. However, it is unclear whether the association with specific inflammatory cytokines is causal or due to bias. To investigate the relationship between genetically predicted levels of inflammatory cytokines and sarcopenia, we performed bidirectional two-sample Mendelian randomization (MR) and systematic review and meta-analysis.

The genome-wide association study data of 44 inflammatory cytokines and 4 sarcopenia-associated traits were selected. A bidirectional MR analysis was performed. We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and clinicaltrials.gov from inception to October 12, 2023, for eligible studies. The primary outcomes were serum insulin-like growth factor-1 (IGF-1) levels. A systematic review and meta-analysis were performed.

We found IGF-1 was associated with the decrease in hand grip strength (left) (β=-0.032, SE=0.0084, P=1.25×10-4). No pleiotropy was detected. Conversely, we didn't find any sarcopenia-associated traits significantly affected inflammatory cytokines. A total of 20 studies with 404061 participants were included in our systematic review and meta-analysis. The pooled data indicated IGF-1 level in the sarcopenia group was lower than that in the non-sarcopenia group (SMD = -0.53, 95% CI [-0.61 to -0.45], P < 0.00001).

Our study will provide evidence for diagnostic or therapeutic targets for sarcopenia. Serological diagnostic tools and molecular targeted therapeutic drugs can be developed based on IGF-1 in the future.

In our study, MR and clinical data support a causal effect of inflammatory cytokines on sarcopenia, especially IGF-1. This finding requires further validation in the large-scale MR using multi-ethnic cohorts and IGF-1 isoform-specific assays.