| Autor: |
Wang Y; Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing 100871, China., Li H; School of Public Health, Key Lab of Public Health Safety of the Ministry of Education and NHC Key Lab of Health Technology Assessment of the Ministry of Health, Fudan University, Shanghai 200032, China., Huang J; Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing 100871, China., Jiang M; Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing 100871, China., Tian S; Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing 100871, China., Liu S; Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing 100871, China., Zhang L; Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University and Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing 100069, China., Wu S; Department of Occupational and Environmental Health, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China.; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, Shaanxi 710049, China.; Key Laboratory of Trace Elements and Endemic Diseases in Ministry of Health, Xi'an, Shaanxi 710049, China.; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, Xi'an, Shaanxi 710049, China., Kan H; School of Public Health, Key Lab of Public Health Safety of the Ministry of Education and NHC Key Lab of Health Technology Assessment of the Ministry of Health, Fudan University, Shanghai 200032, China.; IRDR ICoE on Risk Interconnectivity and Governance on Weather/Climate Extremes Impact and Public Health, Fudan University, Shanghai 200438, China.; National Center for Children's Health, Children's Hospital of Fudan University, Shanghai 201102, China., Gao X; Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing 100871, China.; Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing 100871, China.; Peking University Institute of Environmental Medicine, Beijing 100191, China.; Center for Healthy Aging, Peking University Health Science Center, Beijing 100083, China. |
| Abstrakt: |
The circadian rhythm regulates many crucial physiological processes, impacting human aging and aging-related outcomes. Observational evidence links circadian rhythm disturbance to PM 2.5 exposure, yet the underlying DNA methylation mechanisms remain unclear due to limited PM 2.5 -dominated experimental settings. Therefore, we investigated the associations between short-term PM 2.5 exposure and DNA methylation changes of 1188 CpG candidates across circadian genes among 32 young adults in the FDU study, with the validation in 26 individuals from the PKU study. Further mediation analyses tested whether DNA methylation of circadian genes could mediate the influence of PM 2.5 on aging measured by three epigenetic ages: DNAmGrimAge, DunedinPoAm, and the mortality risk score. We identified three CpG sites associated with personal PM 2.5 exposure: cg01248361 ( CSNK2A2 ), cg17728065 ( RORA ), and cg22513396 ( PRKAG2 ). Acute effects of PM 2.5 on the three loci could be mediated by several circulating biomarkers, including MDA and EGF, with up to ∼30% of mediated proportions. Three loci further showed varying potentials in mediating the aging acceleration effect of PM 2.5 . Locus cg17728065 is the key site exhibiting a robust mediating effect (7.54-12.52%) on PM 2.5 -induced aging acceleration. Our findings demonstrated that PM 2.5 , even short-term peaks, could leave imprints on human aging via inducing aberrant temporal fluctuation in circadian homeostasis captured by DNA methylation profiles. |
