Unveiling the muscle-brain axis: A bidirectional mendelian randomization study investigating the causal relationship between sarcopenia-related traits and brain aging

Observational studies suggest an association between sarcopenia-related traits and brain aging, but whether this association reflects a causal relationship remains unclear. This study aims to employ Mendelian randomization (MR) methods to investigate the causal impact of sarcopenia-related traits on brain aging. This study presents a comprehensive analysis of genome-wide association study (GWAS) summary data associated with sarcopenia-related traits. The data were derived from a large-scale cohort, encompassing measures such as grip strength, lean body mass, and walking pace. Measurements of brain aging were obtained from neuroimaging genetics, utilizing meta-analysis (ENIGMA) to combine magnetic resonance imaging (MRI) data from 33,992 participants. The primary methodology employed in this analysis was the inverse-variance-weighted method (IVW). Additionally, sensitivity analyses were conducted, to assess heterogeneity and pleiotropy. Appendicular lean mass(ALM) is negatively correlated with Pallidum aging; Whole body fat-free mass shows a negative correlation with Amygdala aging; Leg fat-free mass (left) and Leg fat-free mass (right) are negatively correlated with Pallidum aging; Usual walking pace is positively correlated with Nucleus Accumbens aging. Cerebellum WM aging is negatively correlated with Leg fat-free mass (left) and Leg fat-free mass (right); Hippocampus aging is negatively correlated with Hand grip strength (left) and Hand grip strength (right). Ventricles aging is positively correlated with Usual walking pace; Nucleus Accumbens aging is positively correlated with Leg fat-free mass (left) and Leg fat-free mass (right); Putamen aging is positively correlated with ALM. Our study confirms that reduced muscle mass speeds up brain aging. Walking too fast raises the risk of brain aging, while maintaining or increasing appendicular lean mass, overall muscle mass, and muscle mass in both legs lowers the risk of brain aging.