Effects of lithium nickel manganese cobalt oxide exposure on biological age acceleration: Insights from metabolomics

The Lithium nickel manganese cobalt oxide (NCM) is a representative new energy material widely used in industry and daily life, but the systemic health influence of exposure to NCM remained largely unknown. This study aimed to reveal the impacts of NCM exposure on biological age acceleration (BAA) and metabolic alteration, as well as the mediating roles of metabolites. NCM exposure was assessed through three methods: external exposure, biomarker of exposure to NCM mixture (Li, Ni, Co, and Mn), with a particular focus on Li exposure. BAA was calculated using the Klemera and Doubal methods, and untargeted metabolomics was conducted among a representative sample of participants (n = 100). High NCM external exposure showed higher BAA than those with low exposure (median BAA: 0.11 vs. -0.32 years), and increased dose-response relationships between NCM exposure biomarker and BAA were observed using two multi-exposure models. Li was the critical component to NCM exposure effects (weight = 0.793). The "meet-in-the-middle" approach identified twenty-eight metabolites associated with both external and biomarkers of exposure to NCM, Li exposure, and BAA (VIP ≥ 1 and FDR ≤ 0.05). Five key metabolites including TG(50:0)-TG(18:0/16:0/16:0), eicosadienoic acid, Gly-Glu, 2-Oxoarginine, and TG(55:1)-TG(16:0/18:1/21:0) mediated 18.10 %-89.40 % of NCM exposure-BAA association. Our findings provide epidemiological evidence on the hazardous NCM exposure and shed light on metabolic biomarkers for the identification and intervention of accelerated aging among populations.