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• Epigenetic Clock: Just a Convenient Marker or an Active Driver of Aging?

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         headline:Role of epigenetics in human aging and longevity: genome-wide DNA methylation profile in centenarians and centenarians’ offspring
         description: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.
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               name:Dipartimento di Informatica, Sistemistica e Comunicazione, Universita’ degli Studi di Milano-Bicocca, Milan, Italy
               type:PostalAddress
            type:Organization
      name:Daniel Remondini
      affiliation:
            name:Bologna University
            address:
               name:Physics Department, Bologna University, Bologna, Italy
               type:PostalAddress
            type:Organization
      name:Giulia Ogliari
      affiliation:
            name:IRCCS Ca’ Granda Foundation Maggiore Policlinico Hospital
            address:
               name:Geriatric Unit, IRCCS Ca’ Granda Foundation Maggiore Policlinico Hospital, Milan, Italy
               type:PostalAddress
            type:Organization
      name:Rita Ostan
      affiliation:
            name:University of Bologna
            address:
               name:Department of Experimental Pathology, University of Bologna, Bologna, Italy
               type:PostalAddress
            type:Organization
            name:University of Bologna
            address:
               name:CIG-Interdepartmental Center “L. Galvani”, University of Bologna, Bologna, Italy
               type:PostalAddress
            type:Organization
      name:Laura Bucci
      affiliation:
            name:University of Bologna
            address:
               name:Department of Experimental Pathology, University of Bologna, Bologna, Italy
               type:PostalAddress
            type:Organization
            name:University of Bologna
            address:
               name:CIG-Interdepartmental Center “L. Galvani”, University of Bologna, Bologna, Italy
               type:PostalAddress
            type:Organization
      name:Silvia M. Sirchia
      affiliation:
            name:Università degli Studi di Milano
            address:
               name:Medical Genetics Unit, Dipartimento di Medicina, Chirurgia e Odontoiatria, Università degli Studi di Milano, Milan, Italy
               type:PostalAddress
            type:Organization
      name:Silvia Tabano
      affiliation:
            name:Università degli Studi di Milano
            address:
               name:Medical Genetics Unit, Dipartimento di Medicina, Chirurgia e Odontoiatria, Università degli Studi di Milano, Milan, Italy
               type:PostalAddress
            type:Organization
      name:Francesco Cavagnini
      affiliation:
            name:Istituto Auxologico Italiano IRCCS
            address:
               name:Centro di Ricerche e Tecnologie Biomediche, Istituto Auxologico Italiano IRCCS, Milan, Italy
               type:PostalAddress
            type:Organization
      name:Daniela Monti
      affiliation:
            name:University of Florence
            address:
               name:Department of Experimental Pathology and Oncology, University of Florence, Florence, Italy
               type:PostalAddress
            type:Organization
      name:Claudio Franceschi
      affiliation:
            name:University of Bologna
            address:
               name:Department of Experimental Pathology, University of Bologna, Bologna, Italy
               type:PostalAddress
            type:Organization
            name:University of Bologna
            address:
               name:CIG-Interdepartmental Center “L. Galvani”, University of Bologna, Bologna, Italy
               type:PostalAddress
            type:Organization
      name:Anna Maria Di Blasio
      affiliation:
            name:Istituto Auxologico Italiano IRCCS
            address:
               name:Centro di Ricerche e Tecnologie Biomediche, Istituto Auxologico Italiano IRCCS, Milan, Italy
               type:PostalAddress
            type:Organization
      name:Giovanni Vitale
      affiliation:
            name:Istituto Auxologico Italiano IRCCS
            address:
               name:Centro di Ricerche e Tecnologie Biomediche, Istituto Auxologico Italiano IRCCS, Milan, Italy
               type:PostalAddress
            type:Organization
            name:University of Milan
            address:
               name:Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Centro di Ricerche e Tecnologie Biomediche, Istituto Auxologico Italiano IRCCS, Milan, Italy
      name:Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
      name:Geriatric Unit, IRCCS Ca’ Granda Foundation Maggiore Policlinico Hospital, Milan, Italy
      name:Centro di Ricerche e Tecnologie Biomediche, Istituto Auxologico Italiano IRCCS, Milan, Italy
      name:Dipartimento di Informatica, Sistemistica e Comunicazione, Universita’ degli Studi di Milano-Bicocca, Milan, Italy
      name:Physics Department, Bologna University, Bologna, Italy
      name:Geriatric Unit, IRCCS Ca’ Granda Foundation Maggiore Policlinico Hospital, Milan, Italy
      name:Department of Experimental Pathology, University of Bologna, Bologna, Italy
      name:CIG-Interdepartmental Center “L. Galvani”, University of Bologna, Bologna, Italy
      name:Department of Experimental Pathology, University of Bologna, Bologna, Italy
      name:CIG-Interdepartmental Center “L. Galvani”, University of Bologna, Bologna, Italy
      name:Medical Genetics Unit, Dipartimento di Medicina, Chirurgia e Odontoiatria, Università degli Studi di Milano, Milan, Italy
      name:Medical Genetics Unit, Dipartimento di Medicina, Chirurgia e Odontoiatria, Università degli Studi di Milano, Milan, Italy
      name:Centro di Ricerche e Tecnologie Biomediche, Istituto Auxologico Italiano IRCCS, Milan, Italy
      name:Department of Experimental Pathology and Oncology, University of Florence, Florence, Italy
      name:Department of Experimental Pathology, University of Bologna, Bologna, Italy
      name:CIG-Interdepartmental Center “L. Galvani”, University of Bologna, Bologna, Italy
      name:Centro di Ricerche e Tecnologie Biomediche, Istituto Auxologico Italiano IRCCS, Milan, Italy
      name:Centro di Ricerche e Tecnologie Biomediche, Istituto Auxologico Italiano IRCCS, Milan, Italy
      name:Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
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