Decline in genomic DNA methylation through aging in a cohort of elderly subjects.
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 (beta=-0.12 %5mC/year, p=0.0005). A weaker association was observed with LINE-1 elements (beta=-0.06 %5mC/year, p=0.049). We observed a significant decrease in average Alu methylation over time, with a -0.2 %5mC 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 (beta=-0.089 %5mC/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.
Bollati
Valentina
V
Center of Molecular and Genetic Epidemiology, Department of Environmental and Occupational Health, University of Milan & IRCCS Maggiore Hospital, Mangiagalli and Regina Elena Foundation, Milan, Italy.
Schwartz
Joel
J
Wright
Robert
R
Litonjua
Augusto
A
Tarantini
Letizia
L
Suh
Helen
H
Sparrow
David
D
Vokonas
Pantel
P
Baccarelli
Andrea
A
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D001483:Base Sequence; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D019175:DNA Methylation; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017421:Sequence Analysis; D013997:Time Factors