title: Role of epigenetics in human aging and longevity: genome-wide DNA methylation profile in centenarians and centenarians' offspring.
abstract: 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 non-long-lived 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 genome-wide CpG methylation analysis. We observed an age-related 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 age-associated diseases. Genome-wide methylation analysis evidenced DNA methylation profiles specific for aging and longevity: (1) aging-associated 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 non-long-lived parents, hypothesizing a role for these genes in human longevity. Our results suggest that a better preservation of DNA methylation status, a slower cell growing/metabolism, 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 insulin-like growth factor I system impairment on the modulation of human lifespan.
authors.affiliation: Centro di Ricerche e Tecnologie Biomediche, Istituto Auxologico Italiano IRCCS, Via Zucchi 18, Cusano Milanino, 20095, Milan, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Gentilini
authors.forename: Daniela
authors.initials: D
authors.lastname: Mari
authors.forename: Davide
authors.initials: D
authors.lastname: Castaldi
authors.forename: Daniel
authors.initials: D
authors.lastname: Remondini
authors.forename: Giulia
authors.initials: G
authors.lastname: Ogliari
authors.forename: Rita
authors.initials: R
authors.lastname: Ostan
authors.forename: Laura
authors.initials: L
authors.lastname: Bucci
authors.forename: Silvia M
authors.initials: SM
authors.lastname: Sirchia
authors.forename: Silvia
authors.initials: S
authors.lastname: Tabano
authors.forename: Francesco
authors.initials: F
authors.lastname: Cavagnini
authors.forename: Daniela
authors.initials: D
authors.lastname: Monti
authors.forename: Claudio
authors.initials: C
authors.lastname: Franceschi
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Di Blasio
authors.forename: Giovanni
authors.initials: G
authors.lastname: Vitale
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D005500:Follow-Up Studies; D055106:Genome-Wide Association Study; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D004247:DNA