Long-term exposure to air pollution, proteomic aging clocks, and liver-related outcomes in Chinese adults.
Huang Y., Sun D., Lv A., Lv J., Yu C., Sun D., Pei P., Yang L., Chen Y., Du H., Huang D., Yang X., Chen J., Wu S., Zheng M-H., Chen Z., Li L., Pang Y., China Kadoorie Biobank Collaborative Group .
Although air pollution is recognized as a contributor to accelerated biological aging, its associations with clinically significant liver-related outcomes and the potential role of proteomic aging remain unclear. We aimed to evaluate the associations of key air pollutants with liver-related outcomes and the potential mediating role of proteomic aging clocks. Among 504,006 China Kadoorie Biobank participants without liver disease or cancer, we used time-varying Cox regression to assess associations of PM2.5, PM10, NO2, and warm-season O3, and their mixtures with liver-related events (LRE) and liver-related mortality (LRM), and mediation analyses to examine the role of proteomic aging clocks (i.e., ProtAge). Long-term exposure to PM2.5, PM10, NO2, and warm-season O3 showed significant positive associations with LRE, while PM2.5, PM10, and NO2 were also positively associated with LRM. A 1-unit increment in the weighted pollutant score was associated with an 81% higher risk of LRE (hazard ratio [HR]=1.81 [1.65-1.98]) and a 17% higher risk of LRM (HR=1.17 [1.05-1.31]). Acceleration in ProtAge was associated with higher risks of LRE (HR=1.86 [1.16-2.97]) and LRM (HR=4.43 [3.02-6.50]). ProtAge accounted for an estimated 7.1% and 12.5% of the associations of pollutant mixtures with LRE and LRM, respectively. Among proteins in ProtAge, CD248, GDF15, TNFRSF6B, and XG showed concordant associations in pollutant mixture-protein and protein-LRE analyses. Long-term air pollution was associated with higher risks of clinically significant liver-related outcomes. These findings suggest a possible role of proteomic aging in the association between air pollution and liver-related outcomes, warranting further investigation.