Circulating Neurofilament Light Chain Levels Increase with Age and Are Associated with Worse Physical Function and Body Composition in Men but Not in Women

This study aimed to assess the relationship between age-related changes in Neurofilament Light Chain (NFL), a marker of neuronal function, and various factors including muscle function, body composition, and metabolomic markers. The study included 40 participants, aged 20 to 85 years. NFL levels were measured, and muscle function, body composition, and metabolomic markers were assessed. NFL levels increased significantly with age, particularly in men. Negative correlations were found between NFL levels and measures of muscle function, such as grip strength, walking speed, and chair test performance, indicating a decline in muscle performance with increasing NFL. These associations were more pronounced in men. NFL levels also negatively correlated with muscle quality in men, as measured by 50 kHz phase angle. In terms of body composition, NFL was positively correlated with markers of fat mass and negatively correlated with markers of muscle mass, predominantly in men. Metabolomic analysis revealed significant associations between NFL levels and specific metabolites, with gender-dependent relationships observed. This study provides insights into the relationship between circulating serum NFL, muscle function, and aging. Our findings hint at circulating NFL as a potential early marker of age-associated neurodegenerative processes, especially in men.