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.

Role of epigenetics in human aging and longevity : genome-wide DNA methylation profile in centenarians and centenarians' offspring / D. Gentilini, D. Mari, D. Castaldi, D. Remondini, G. Ogliari, R. Ostan, L. Bucci, S.M. Sirchia, S. Tabano, F. Cavagnini, D. Monti, C. Franceschi, A.M. Di Blasio, G. Vitale. - In: AGE. - ISSN 1574-4647. - 35:5(2013 Oct), pp. 1961-1973.

Role of epigenetics in human aging and longevity : genome-wide DNA methylation profile in centenarians and centenarians' offspring

D. Gentilini
Primo
;
D. Mari;G. Ogliari;S.M. Sirchia;S. Tabano;F. Cavagnini;G. Vitale
Ultimo
2013

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.
Aging; Centenarians' offspring; DNA methylation; Epigenetics; Longevity. Centenarians
Settore MED/03 - Genetica Medica
Settore BIO/11 - Biologia Molecolare
Settore MED/13 - Endocrinologia
Settore MED/09 - Medicina Interna
ott-2013
AGE
Article (author)
File in questo prodotto:
File Dimensione Formato  
fulltext.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 576.92 kB
Formato Adobe PDF
576.92 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/204466
Citazioni
  • ???jsp.display-item.citation.pmc??? 70
  • Scopus 163
  • ???jsp.display-item.citation.isi??? 6
social impact