2026-04-29T01:00:01Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/190932025-04-04T16:03:55Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19608

00925njm 22002777a 4500 dc Jiang, Enoch X author Domingo-Relloso, Arce author Abuawad, Ahlam author Haack, Karin author Tellez-Plaza, Maria author Fallin, M Daniele author Umans, Jason G author Best, Lyle G author Zhang, Ying author Kupsco, Allison author Belsky, Daniel W author Cole, Shelley A author Navas-Acien, Ana author 2023-12 Background: Inorganic arsenic (As) may increase the risk of cardiovascular disease (CVD) and all-cause mortality through accelerated aging, which can be estimated using epigenetic-based measures. Objectives: We evaluated three DNA methylation-based aging measures (PhenoAge, GrimAge, DunedinPACE) (epigenetic aging measures) as potential mediators of the previously reported association of As exposure with CVD incidence, CVD mortality, and all-cause mortality in the Strong Heart Study (SHS), an epidemiological cohort of American Indian adults. Methods: Blood DNA methylation and urinary As levels were measured in 2,323 SHS participants (41.5% men, mean age of 55 years old). PhenoAge and GrimAge values were calculated using a residual-based method. We tested the association of urinary As with epigenetic aging measures using linear regression, the association of epigenetic aging measures with the three health outcomes using additive hazards models, and the mediation of As-related CVD incidence, CVD mortality, and all-cause mortality by epigenetic aging measures using the product of coefficients method. Results: SHS participants with higher vs. lower urinary As levels had similar PhenoAge age, older GrimAge age, and faster DunedinPACE. An interquartile range increase in urinary As was associated with higher of PhenoAge age acceleration [mean difference (95% confidence interval) = 0.48 (0.17, 0.80) years], GrimAge age acceleration [0.80 (0.60, 1.00) years], and DunedinPACE [0.011 (0.005, 0.018)], after adjusting for age, sex, center location, genetic components, smoking status, and body mass index. Of the 347 incident CVD events per 100,000 person-years associated with a doubling in As exposure, 21.3% (9.1, 57.1) and 22.6% (9.5, 56.9), were attributable to differences in GrimAge and DunedinPACE, respectively. Discussion: Arsenic exposure was associated with older GrimAge and faster DunedinPACE measures of biological age. Furthermore, accelerated biological aging measured from DNA methylation accounted for a relevant fraction of As-associated risk for CVD, CVD mortality, and all-cause mortality in the SHS, supporting the role of As in accelerated aging. Research of the biological underpinnings can contribute to a better understanding of the role of aging in arsenic-related disease. https://doi.org/10.1289/EHP11981. Environ Health Perspect. 2023 Dec;131(12):127016. http://hdl.handle.net/20.500.12105/19093 38133959 10.1289/EHP11981 1552-9924 Environmental health perspectives Arsenic Exposure and Epigenetic Aging: The Association with Cardiovascular Disease and All-Cause Mortality in the Strong Heart Study