role of epigenetics in human aging and longevity genomewide dna methylation profile in centenarians and centenarians offspring the role of epigenetics in the modulation of longevity has not been studied in humans to this aim 1 we evaluated the dna methylation from peripheral leukocytes of 21 female centenarians their 21 female offspring 21 offspring of both nonlonglived parents and 21 young women through elisa assay pyrosequencing analysis of alu sequences and quantification of methylation in cpg repeats outside cpg islands 2 we compared the dna methylation profiles of these populations through infinium array for genomewide cpg methylation analysis we observed an agerelated decrease in global dna methylation and a delay of this process in centenarians offspring interestingly literature data suggest a link between the loss of dna methylation observed during aging and the development of ageassociated diseases genomewide methylation analysis evidenced dna methylation profiles specific for aging and longevity 1 agingassociated dna hypermethylation occurs predominantly in genes involved in the development of anatomical structures organs and multicellular organisms and in the regulation of transcription 2 genes involved in nucleotide biosynthesis metabolism and control of signal transmission are differently methylated between centenarians offspring and offspring of both nonlonglived parents hypothesizing a role for these genes in human longevity our results suggest that a better preservation of dna methylation status a slower cell growingmetabolism and a better control in signal transmission through epigenetic mechanisms may be involved in the process of human longevity these data fit well with the observations related to the beneficial effects of mild hypothyroidism and insulinlike growth factor i system impairment on the modulation of human lifespan