Browsing by Author "Sehl, Mary E."

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    DNA methylation age is elevated in breast tissue of healthy women
    (Springer, 2017-07) Sehl, Mary E.; Henry, Jill E.; Storniolo, Anna Maria; Ganz, Patricia A.; Horvath, Steve; Medicine, School of Medicine
    BACKGROUND: Limited evidence suggests that female breast tissue ages faster than other parts of the body according to an epigenetic biomarker of aging known as the "epigenetic clock." However, it is unknown whether breast tissue samples from healthy women show a similar accelerated aging effect relative to other tissues, and what could drive this acceleration. The goal of this study is to validate our initial finding of advanced DNA methylation (DNAm) age in breast tissue, by directly comparing it to that of peripheral blood tissue from the same individuals, and to do a preliminary assessment of hormonal factors that could explain the difference. METHODS: We utilized n = 80 breast and 80 matching blood tissue samples collected from 40 healthy female participants of the Susan G. Komen Tissue Bank at the Indiana University Simon Cancer Center who donated these samples at two time points spaced at least a year apart. DNA methylation levels (Illumina 450K platform) were used to estimate the DNAm age. RESULTS: DNAm age was highly correlated with chronological age in both peripheral blood (r = 0.94, p < 0.0001) and breast tissues (r = 0.86, p < 0.0001). A measure of epigenetic age acceleration (age-adjusted DNAm Age) was substantially increased in breast relative to peripheral blood tissue (p = 1.6 × 10-11). The difference between DNAm age of breast and blood decreased with advancing chronologic age (r = -0.53, p = 4.4 × 10-4). CONCLUSIONS: Our data clearly demonstrate that female breast tissue has a higher epigenetic age than blood collected from the same subject. We also observe that the degree of elevation in breast diminishes with advancing age. Future larger studies will be needed to examine associations between epigenetic age acceleration and cumulative hormone exposure.
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    The effects of lifetime estrogen exposure on breast epigenetic age
    (American Association for Cancer Research, 2021) Sehl, Mary E.; Henry, Jill E.; Storniolo, Anna M.; Horvath, Steve; Ganz, Patricia A.; Medicine, School of Medicine
    Background: Estrogens are thought to contribute to breast cancer risk through cell cycling and accelerated breast aging. We hypothesize that lifetime estrogen exposure drives early epigenetic breast aging observed in healthy women. In this study, we examined associations between hormonal factors and epigenetic aging measures in healthy breast tissues. Methods: We extracted DNA from breast tissue specimens from 192 healthy female donors to the Susan G. Komen Tissue Bank at the Indiana University Simon Cancer Center. Methylation experiments were performed using the Illumina EPIC 850K array platform. Age-adjusted regression models were used to examine for associations between factors related to estrogen exposure and five DNA methylation-based estimates: Grim age, pan-tissue age, Hannum age, phenotypic age, and skin and blood clock age. Results: Women were aged 19-90 years, with 95 premenopausal, and 97 nulliparous women. The age difference (Grim age - chronologic age) was higher at earlier ages close to menarche. We found significant associations between earlier age at menarche and age-adjusted accelerations according to the Grim clock, the skin and blood clock, and between higher body mass index (BMI) and age-adjusted accelerations in the Grim clock, Hannum clock, phenotypic clock, and skin and blood clock. Conclusions: Earlier age at menarche and higher BMI are associated with elevations in DNA methylation-based age estimates in healthy breast tissues, suggesting that cumulative estrogen exposure drives breast epigenetic aging. Impact: Epigenetic clock measures may help advance inquiry into the relationship between accelerated breast tissue aging and an elevated incidence of breast cancer in younger women.
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    The impact of reproductive factors on DNA methylation-based telomere length in healthy breast tissue
    (Springer Nature, 2022-04-13) Sehl, Mary E.; Henry, Jill E.; Storniolo, Anna Maria; Horvath, Steve; Ganz, Patricia A.; Medicine, School of Medicine
    Estrogen promotes breast tissue proliferation and telomerase activation. We investigated the effects of reproductive history on cell cycling and telomere length using a DNA methylation-based estimate of telomere length (DNAmTL) in breast and blood from healthy women donors. We demonstrate that DNAmTL is shorter in breast than in blood, and that nulliparous women have longer age-adjusted DNAmTL in both breast and blood, potentially explaining their higher risk of breast cancer.