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      Air pollution and epigenetic aging among Black and White women in the US

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          Abstract

          Background:

          DNA methylation-based measures of biological aging have been associated with air pollution and may link pollutant exposures to aging-related health outcomes. However, evidence is inconsistent and there is little information for Black women.

          Objective:

          We examined associations of ambient particulate matter <2.5 μm and <10 μm in diameter (PM 2.5 and PM 10) and nitrogen dioxide (NO 2) with DNA methylation, including epigenetic aging and individual CpG sites, and evaluated whether associations differ between Black and non-Hispanic White (NHW) women.

          Methods:

          Validated models were used to estimate annual average outdoor residential exposure to PM 2.5, PM 10, and NO 2 in a sample of self-identified Black (n=633) and NHW (n=3493) women residing in the contiguous US. We used sampling-weighted generalized linear regression to examine the effects of pollutants on six epigenetic aging measures (primary: DunedinPACE, GrimAgeAccel, and PhenoAgeAccel; secondary: Horvath intrinsic epigenetic age acceleration [EAA], Hannum extrinsic EAA, and skin & blood EAA) and epigenome-wide associations for individual CpG sites. Wald tests of nested models with and without interaction terms were used to examine effect measure modification by race/ethnicity.

          Results:

          Black participants had higher median air pollution exposure than NHW participants. GrimAgeAccel was associated with both PM 10 and NO 2 among Black participants, (Q4 versus Q1, PM 10: β=1.09, 95% CI: 0.16–2.03; NO 2: β=1.01, 95% CI 0.08–1.94) but not NHW participants ( p-for-heterogeneity: PM 10=0.10, NO 2=0.20). In Black participants, we also observed a monotonic exposure–response relationship between NO 2 and DunedinPACE (Q4 versus Q1, NO 2: β=0.029, 95% CI: 0.004–0.055; p-for-trend=0.03), which was not observed in NHW participants ( p-for-heterogeneity=0.09). In the EWAS, pollutants were significantly associated with differential methylation at 19 CpG sites in Black women and one in NHW women.

          Conclusions:

          In a US-wide cohort study, our findings suggest that air pollution is associated with DNA methylation alterations consistent with higher epigenetic aging among Black, but not NHW, women.

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          Most cited references57

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          DNA methylation age of human tissues and cell types

          Background It is not yet known whether DNA methylation levels can be used to accurately predict age across a broad spectrum of human tissues and cell types, nor whether the resulting age prediction is a biologically meaningful measure. Results I developed a multi-tissue predictor of age that allows one to estimate the DNA methylation age of most tissues and cell types. The predictor, which is freely available, was developed using 8,000 samples from 82 Illumina DNA methylation array datasets, encompassing 51 healthy tissues and cell types. I found that DNA methylation age has the following properties: first, it is close to zero for embryonic and induced pluripotent stem cells; second, it correlates with cell passage number; third, it gives rise to a highly heritable measure of age acceleration; and, fourth, it is applicable to chimpanzee tissues. Analysis of 6,000 cancer samples from 32 datasets showed that all of the considered 20 cancer types exhibit significant age acceleration, with an average of 36 years. Low age-acceleration of cancer tissue is associated with a high number of somatic mutations and TP53 mutations, while mutations in steroid receptors greatly accelerate DNA methylation age in breast cancer. Finally, I characterize the 353 CpG sites that together form an aging clock in terms of chromatin states and tissue variance. Conclusions I propose that DNA methylation age measures the cumulative effect of an epigenetic maintenance system. This novel epigenetic clock can be used to address a host of questions in developmental biology, cancer and aging research.
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            Structural racism and health inequities in the USA: evidence and interventions

            The Lancet, 389(10077), 1453-1463
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              An epigenetic biomarker of aging for lifespan and healthspan

              Identifying reliable biomarkers of aging is a major goal in geroscience. While the first generation of epigenetic biomarkers of aging were developed using chronological age as a surrogate for biological age, we hypothesized that incorporation of composite clinical measures of phenotypic age that capture differences in lifespan and healthspan may identify novel CpGs and facilitate the development of a more powerful epigenetic biomarker of aging. Using an innovative two-step process, we develop a new epigenetic biomarker of aging, DNAm PhenoAge, that strongly outperforms previous measures in regards to predictions for a variety of aging outcomes, including all-cause mortality, cancers, healthspan, physical functioning, and Alzheimer's disease. While this biomarker was developed using data from whole blood, it correlates strongly with age in every tissue and cell tested. Based on an in-depth transcriptional analysis in sorted cells, we find that increased epigenetic, relative to chronological age, is associated with increased activation of pro-inflammatory and interferon pathways, and decreased activation of transcriptional/translational machinery, DNA damage response, and mitochondrial signatures. Overall, this single epigenetic biomarker of aging is able to capture risks for an array of diverse outcomes across multiple tissues and cells, and provide insight into important pathways in aging.
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                Author and article information

                Journal
                7807270
                22115
                Environ Int
                Environ Int
                Environment international
                0160-4120
                1873-6750
                24 November 2023
                November 2023
                17 October 2023
                16 February 2024
                : 181
                : 108270
                Affiliations
                [a ]Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, 123 W. Franklin St., Chapel Hill, NC 27517, USA
                [b ]Epidemiology Branch, National Institute of Environmental Health Sciences, 111 TW Alexander Dr, Research Triangle Park, NC 27709, USA
                [c ]Departments of Cancer Epidemiology and Breast Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA
                [d ]Departments of Environmental & Occupational Health Sciences, Medicine, and Epidemiology University of Washington, 4225 Roosevelt Way NE, Seattle, WA 98105, USA
                Author notes
                [* ]Corresponding author at: P.O. Box 12233, Mail Drop A3-05, Durham, NC 27709, USA. skoenigsberg@ 123456unc.edu (S.H. Koenigsberg), alexandra.white@ 123456nih.gov (A.J. White).
                Article
                NIHMS1943037
                10.1016/j.envint.2023.108270
                10872847
                37890265
                e8e54fb4-2930-431d-8ccb-15f3c95d0524

                This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/).

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                Categories
                Article

                air pollution,dna methylation,particulate matter,epigenetic age,epigenome-wide association study

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