Frailty is an underappreciated but modifiable clinical syndrome, but little about how air quality improvements could influence frailty progression is known. Here, we utilized two Chinese cohorts with repeated follow-up visits to address this knowledge gap and explored the underlying DNA methylation mechanisms. We first conducted a multistate modeling analysis in the Chinese Longitudinal Healthy Longevity Study (CLHLS), a nationwide cohort with 21,654 older adults who had participated in at least two survey waves. An interquartile range reduction in PM2.5 exposure increased the likelihood of improvement for frail/prefrail individuals by more than 50% while lowering their risks of worsening frailty or mortality. A quasi-experimental study within a CLHLS subcohort of 1816 adults, leveraging the implementation of China's Clean Air Act, further validated these findings. Additionally, in the Guangxi Eco-Environmental Health and Aging Study─a regional prospective cohort based in Guilin, China─we included 235 older adults with follow-up data and identified three frailty-related CpG sites that were associated with PM2.5 exposure. The CpG site cg25453797 mapped to the PRKCE gene was robustly associated with the change in frailty. These findings demonstrate that air quality improvement benefits older adults by alleviating the frailty burden. DNA methylation may serve as a potential biomarker to capture the health benefits of environmental policy interventions.
Keywords: DNA methylation; PM2.5; air pollution; clean air policy; frailty.