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

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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.

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Acknowledgments

Financial support to this work has been partially provided by the Italian Ministry of University and Research (MIUR) and by the Istituto Auxologico Italiano. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors would like to thank the Register Office of the city of Milan for its contribution in the collection of data.

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Authors and Affiliations

  1. Centro di Ricerche e Tecnologie Biomediche, Istituto Auxologico Italiano IRCCS, Via Zucchi 18, Cusano Milanino, 20095, Milan, Italy

    Davide Gentilini, Davide Castaldi, Francesco Cavagnini, Anna Maria Di Blasio & Giovanni Vitale

  2. Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy

    Daniela Mari & Giovanni Vitale

  3. Geriatric Unit, IRCCS Ca’ Granda Foundation Maggiore Policlinico Hospital, Milan, Italy

    Daniela Mari & Giulia Ogliari

  4. Dipartimento di Informatica, Sistemistica e Comunicazione, Universita’ degli Studi di Milano-Bicocca, Milan, Italy

    Davide Castaldi

  5. Physics Department, Bologna University, Bologna, Italy

    Daniel Remondini

  6. Department of Experimental Pathology, University of Bologna, Bologna, Italy

    Rita Ostan, Laura Bucci & Claudio Franceschi

  7. CIG-Interdepartmental Center “L. Galvani”, University of Bologna, Bologna, Italy

    Rita Ostan, Laura Bucci & Claudio Franceschi

  8. Medical Genetics Unit, Dipartimento di Medicina, Chirurgia e Odontoiatria, Università degli Studi di Milano, Milan, Italy

    Silvia M. Sirchia & Silvia Tabano

  9. Department of Experimental Pathology and Oncology, University of Florence, Florence, Italy

    Daniela Monti

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  1. Davide Gentilini
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  2. Daniela Mari
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  3. Davide Castaldi
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  4. Daniel Remondini
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  5. Giulia Ogliari
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  6. Rita Ostan
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  7. Laura Bucci
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  8. Silvia M. Sirchia
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  9. Silvia Tabano
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  10. Francesco Cavagnini
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  11. Daniela Monti
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  12. Claudio Franceschi
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  13. Anna Maria Di Blasio
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  14. Giovanni Vitale
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Correspondence to Giovanni Vitale.

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Gentilini, D., Mari, D., Castaldi, D. et al. Role of epigenetics in human aging and longevity: genome-wide DNA methylation profile in centenarians and centenarians’ offspring. AGE 35, 1961–1973 (2013). https://doi.org/10.1007/s11357-012-9463-1

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  • DOI: https://doi.org/10.1007/s11357-012-9463-1

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