Chronic air pollution drives multimorbidity risk through inflammatory pathways: a national longitudinal study

Multimorbidity is a growing challenge in aging populations, yet the role of chronic air pollution is poorly understood. We investigated the association between long-term exposure to multiple air pollutants and multimorbidity in middle-aged and older adults. We analyzed data from the China Health and Retirement Longitudinal Study (CHARLS, 2011–2020), linking 96,628 observations to the Emission Database for Global Atmospheric Research (EDGAR) v8.1 data. We used restricted cubic splines to assess non-linear relationships, while generalized additive mixed models and fixed-effects models were used to evaluate the main associations, interactions, and subgroup risks. Potential biological mechanisms were explored through transcriptomic analysis and validated experimentally using in vitro (HEK 293 T cells) and in vivo (rat) pollution exposure models. All nine pollutants showed robust, non-linear associations with increased multimorbidity risk, with risks apparent at low exposure levels. Black Carbon had the strongest effect (odds ratio = 1.127, 95% confidence interval: 1.123–1.132, p < 0.001). Significant synergistic interactions were observed, particularly in PM₂.₅, NOₓ, and SO₂, amplifying the risk. Older individuals, women, and frail individuals were the most vulnerable. Mechanistically, air pollution drove complex and organ-specific dysregulation of the pro-inflammatory gene PTGS2—was upregulated in the lung and liver and downregulated in the spleen. Chronic air pollution increases multimorbidity risk; its synergistic and non-linear effects indicate that single-pollutant standards are insufficient. Our study identified inflammation via complex regulation of PTGS2 as a key biological pathway. These findings underscore the urgent need for multi-pollutant regulations and targeted interventions in vulnerable populations.