title: DNA methylation age is elevated in breast tissue of healthy women.
abstract: 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.
authors.affiliation: Medicine, Hematology-Oncology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095, USA.|Biomathematics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095, USA.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Sehl
authors.affiliation: Susan G. Komen Tissue Bank at the Indiana University Simon Cancer Center, Indianapolis, IN, 46202, USA.
authors.forename: Jill E
authors.initials: JE
authors.lastname: Henry
authors.affiliation: Susan G. Komen Tissue Bank at the Indiana University Simon Cancer Center, Indianapolis, IN, 46202, USA.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Storniolo
authors.affiliation: Medicine, Hematology-Oncology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095, USA.|Health Policy and Management, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, 90095, USA.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Ganz
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine, Gonda Research Center, University of California Los Angeles, 695 Charles E. Young Drive South, Box 708822, Los Angeles, CA, 90095-7088, USA. shorvath@mednet.ucla.edu.|Biostatistics, School of Public Health, University of California Los Angeles, Los Angeles, CA, 90095, USA. shorvath@mednet.ucla.edu.
authors.forename: Steve
authors.initials: S
authors.lastname: Horvath
mesh_terms: D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D013048:Specimen Handling; D014015:Tissue Banks; D016387:Women's Health
keywords: Biomarker of aging; Breast cancer; Cell cycling; DNA methylation; Epigenetics; Estrogen; Tissue aging