Manganese Exposure Is Associated with Reduced Grip Strength: Evidence from Humans and Mice

Although excessive manganese (Mn) exposure is known to cause neuromotor function in cases of poisoning, its effect on grip strength (a neuromotor marker) in older adults at environmental levels remains unclear. To investigate this issue, we conducted an integrated investigation combining epidemiology and animal experimentation to examine the association between urinary manganese and grip strength. A cross-sectional study of 375 elderly men (60-74 years) was conducted in Guangxi, China, from 2016 to 2017. Urinary Mn concentrations were determined by ICP-MS, and their associations with grip strength were evaluated using generalized linear models and restricted cubic splines. In parallel, 32 six-week-old male C57BL/6J mice were exposed to 0, 5, 10, or 15 mg/kg MnCl₂·4H₂O via intraperitoneal injection for 6 weeks. Forelimb grip strength of the mice was measured after the final exposure, and mRNA expression of inflammatory markers and cytokines (C reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-α in triceps) in triceps tissue was quantified. The median urinary Mn concentration in the study population was 0.22 μg/g creatinine. After adjusting for confounders, urinary Mn was inversely associated with hand grip strength (highest vs. lowest tertile: β = -3.57 kg; 95% CI: -5.68 to -1.47; <i>p</i>-trend = 0.007). Similarly, in male C57BL/6J mice, grip strengths declined significantly with increasing Mn exposure (<i>p</i>-trend < 0.0001), accompanied by upregulation of the mRNA levels of CRP, IL-6 and TNF-α in muscle tissue. Together, our findings suggest that environmental manganese exposure is inversely associated with grip strength in elderly men. While the manganese doses used in the animal study exceeded typical human environmental exposure, the experimental results further indicate that such grip strength reduction may be linked to muscle inflammation.