Abstract
In humans, leukocyte telomere length (LTL) is positively correlated with lifespan, and shorter LTL is associated with increased risk of age-related disease. In this study we tested for association between telomere length and methylated cytosine levels. Measurements of mean telomere length and DNA methylation at >450,000 CpG sites were obtained for both blood (N = 24) and EBV-transformed cell-line (N = 36) DNA samples from men aged 44–45 years. We identified 65 gene promoters enriched for CpG sites at which methylation levels are associated with leukocyte telomere length, and 36 gene promoters enriched for CpG sites at which methylation levels are associated with telomere length in DNA from EBV-transformed cell-lines. We observed significant enrichment of positively associated methylated CpG sites in subtelomeric loci (within 4 Mb of the telomere) (P < 0.01), and also at loci in imprinted regions (P < 0.001). Our results pave the way for further investigations to help elucidate the relationships between telomere length, DNA methylation and gene expression in health and disease.
Highlights
Human leukocyte telomere length is associated with DNA methylation levels in multiple subtelomeric and imprinted loci
Among 44–45 year-old men, we have identified multiple gene promoters enriched for sites at which methylation levels are associated with telomere length in human blood DNA
We identified 65 gene promoters that contained sites associated with telomere length, which are largely distinct from the loci in which methylation levels have been associated with increasing age[30,31,32,33]
Summary
Human leukocyte telomere length is associated with DNA methylation levels in multiple subtelomeric and imprinted loci. Leukocyte telomere length (LTL) is positively correlated with lifespan, and shorter LTL is associated with increased risk of age-related disease. Mean leukocyte telomere length (LTL) is positively correlated with lifespan[7,8], and has been proposed as a potential biomarker of biological ageing[9,10,11]. In support of this hypothesis, mean LTL is generally shorter in adult men than in women at any given age, consistent with shorter average male life expectancy in most populations[12]. There is evidence for association between maltreatment in childhood and shorter adult LTL24,25, suggesting that early-life exposures may have long-term effects on cellular ageing rates
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