Objective. The role of epigenetics in the modulation of longevity has not been studied in humans. We employed a new experimental model to identify epigenetically modulated genes involved in the process of ageing, healthy ageing and longevity. To this aim 1) we evaluated the DNA methylation from peripheral leukocyte of 21 female centenarians, their 21 female offspring, 21 offspring of both non long-lived parents and 21 young women. Methods. ELISA assay, quantitative PCR-Pyrosequencing analysis of Alu sequences, quantification of methylation in CpG repeats outside CpG islands; 2) we compared the DNA methylation profiles of these populations through a genomewide CpG methylation analysis (Infinium HumanMethylation27 Bead Chip, Illumina). Results. We observed an age-related decrease in global DNA methylation and a delay of this deleterious process in centenarians' offspring. Genome-wide CpG methylation analysis showed higher CpG islands methylation in both centenarians and their offspring compared to offspring of both non long-lived parents. A locus-by-locus analysis of CpG sites differentially methylated between all groups evidenced epigenetic profiles specific for ageing and longevity: 1) Ageing-associated DNA hypermethylation occurs predominantly in genes involved in the development of anatomical structures, organs and multicellular organisms and regulation of transcription; 2) A specific epigenetic modulation of genes involved in nucleotide biosynthesis, metabolism and control of signal transmission may contribute to explain the longer lifespan and healthy ageing of centenarians' offspring.
|Titolo:||Analisi del metiloma negli ultralongevi e nei loro figli e stato di salute|
|Parole Chiave:||Centenarians; Epigenetic; Healthy aging|
|Settore Scientifico Disciplinare:||Settore MED/03 - Genetica Medica|
Settore MED/09 - Medicina Interna
|Data di pubblicazione:||ott-2011|
|Appare nelle tipologie:||01 - Articolo su periodico|