Decline in genomic DNA methylation through aging in a cohort of elderly subjects

Valentina Bollati, Joel Schwartz, Robert Wright, Augusto Litonjua, Letizia Tarantini, Helen Suh, David Sparrow, Pantel Vokonas, Andrea Baccarelli

Research output: Contribution to journalArticlepeer-review

498 Scopus citations

Abstract

Loss of genomic DNA methylation has been found in a variety of common human age-related diseases. Whether DNA methylation decreases over time as individuals age is unresolved. We measured DNA methylation in 1097 blood DNA samples from 718 elderly subjects between 55 and 92 years of age (1-3 samples/subjects), who have been repeatedly evaluated over an 8-year time span in the Boston area Normative Aging Study. DNA methylation was measured using quantitative PCR-Pyrosequencing analysis in Alu and LINE-1 repetitive elements, heavily methylated sequences with high representation throughout the human genome. Age at the visit was negatively associated with Alu element methylation (β = -0.12 %5 mC/year, p = 0.0005). A weaker association was observed with LINE-1 elements (β = -0.06 %5 mC/year, p = 0.049). We observed a significant decrease in average Alu methylation over time, with a -0.2 %5 mC change (p = 0.012) compared to blood samples collected up to 8 years earlier. The longitudinal decline in Alu methylation was linear and highly correlated with time since the first measurement (β = -0.089 %5 mC/year, p < 0.0001). In contrast, average LINE-1 methylation did not vary over time [p = 0.51]. Our results demonstrate a progressive loss of DNA methylation in repetitive elements dispersed throughout the genome.

Original languageEnglish
Pages (from-to)234-239
Number of pages6
JournalMechanisms of Ageing and Development
Volume130
Issue number4
DOIs
StatePublished - Apr 2009
Externally publishedYes

Keywords

  • Aging
  • Epigenetics
  • Methylation
  • Pryrosequencing
  • Repetitive elements

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