Systemic Age-Associated DNA Hypermethylation of ELOVL2 Gene: In Vivo and In Vitro Evidences of a Cell Replication Process

Maria Giulia Bacalini, Joris Deelen, Chiara Pirazzini, Marco De Cecco, Cristina Giuliani, Catia Lanzarini, Francesco Ravaioli, Elena Marasco, Diana Van Heemst, H. Eka D Suchiman, Roderick Slieker, Enrico Giampieri, Rina Recchioni, Fiorella Marcheselli, Stefano Salvioli, Giovanni Vitale, Fabiola Olivieri, Annemieke M W Spijkerman, Martijn E T Dollé, John M. SedivyGastone Castellani, Claudio Franceschi, Pieternella Eline Slagboom, Paolo Garagnani

Research output: Contribution to journalArticle

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Abstract

Epigenetic remodeling is one of the major features of the aging process. We recently demonstrated that DNA methylation of ELOVL2 and FHL2 CpG islands is highly correlated with age in whole blood. Here we investigated several aspects of age-associated hypermethylation of ELOVL2 and FHL2 We showed that ELOVL2 methylation is significantly different in primary dermal fibroblast cultures from donors of different ages. Using epigenomic data from public resources, we demonstrated that most of the tissues show ELOVL2 and FHL2 hypermethylation with age. Interestingly, ELOVL2 hypermethylation was not found in tissues with very low replication rate. We demonstrated that ELOVL2 hypermethylation is associated with in vitro cell replication rather than with senescence. We confirmed intra-individual hypermethylation of ELOVL2 and FHL2 in longitudinally assessed participants from the Doetinchem Cohort Study. Finally we showed that, although the methylation of the two loci is not associated with longevity/mortality in the Leiden Longevity Study, ELOVL2 methylation is associated with cytomegalovirus status in nonagenarians, which could be informative of a higher number of replication events in a fraction of whole-blood cells. Collectively, these results indicate that ELOVL2 methylation is a marker of cell divisions occurring during human aging.

Original languageEnglish
Pages (from-to)1015-1023
Number of pages9
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume72
Issue number8
DOIs
Publication statusPublished - Aug 2017

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Methylation
DNA
Epigenomics
Genes
CpG Islands
DNA Methylation
Cytomegalovirus
Cell Division
Blood Cells
Cohort Studies
Fibroblasts
Tissue Donors
Skin
Mortality
In Vitro Techniques

Keywords

  • Journal Article

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Systemic Age-Associated DNA Hypermethylation of ELOVL2 Gene : In Vivo and In Vitro Evidences of a Cell Replication Process. / Bacalini, Maria Giulia; Deelen, Joris; Pirazzini, Chiara; De Cecco, Marco; Giuliani, Cristina; Lanzarini, Catia; Ravaioli, Francesco; Marasco, Elena; Van Heemst, Diana; Suchiman, H. Eka D; Slieker, Roderick; Giampieri, Enrico; Recchioni, Rina; Marcheselli, Fiorella; Salvioli, Stefano; Vitale, Giovanni; Olivieri, Fabiola; Spijkerman, Annemieke M W; Dollé, Martijn E T; Sedivy, John M.; Castellani, Gastone; Franceschi, Claudio; Slagboom, Pieternella Eline; Garagnani, Paolo.

In: Journals of Gerontology - Series A Biological Sciences and Medical Sciences, Vol. 72, No. 8, 08.2017, p. 1015-1023.

Research output: Contribution to journalArticle

Bacalini, MG, Deelen, J, Pirazzini, C, De Cecco, M, Giuliani, C, Lanzarini, C, Ravaioli, F, Marasco, E, Van Heemst, D, Suchiman, HED, Slieker, R, Giampieri, E, Recchioni, R, Marcheselli, F, Salvioli, S, Vitale, G, Olivieri, F, Spijkerman, AMW, Dollé, MET, Sedivy, JM, Castellani, G, Franceschi, C, Slagboom, PE & Garagnani, P 2017, 'Systemic Age-Associated DNA Hypermethylation of ELOVL2 Gene: In Vivo and In Vitro Evidences of a Cell Replication Process', Journals of Gerontology - Series A Biological Sciences and Medical Sciences, vol. 72, no. 8, pp. 1015-1023. https://doi.org/10.1093/gerona/glw185
Bacalini, Maria Giulia ; Deelen, Joris ; Pirazzini, Chiara ; De Cecco, Marco ; Giuliani, Cristina ; Lanzarini, Catia ; Ravaioli, Francesco ; Marasco, Elena ; Van Heemst, Diana ; Suchiman, H. Eka D ; Slieker, Roderick ; Giampieri, Enrico ; Recchioni, Rina ; Marcheselli, Fiorella ; Salvioli, Stefano ; Vitale, Giovanni ; Olivieri, Fabiola ; Spijkerman, Annemieke M W ; Dollé, Martijn E T ; Sedivy, John M. ; Castellani, Gastone ; Franceschi, Claudio ; Slagboom, Pieternella Eline ; Garagnani, Paolo. / Systemic Age-Associated DNA Hypermethylation of ELOVL2 Gene : In Vivo and In Vitro Evidences of a Cell Replication Process. In: Journals of Gerontology - Series A Biological Sciences and Medical Sciences. 2017 ; Vol. 72, No. 8. pp. 1015-1023.
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T2 - In Vivo and In Vitro Evidences of a Cell Replication Process

AU - Bacalini, Maria Giulia

AU - Deelen, Joris

AU - Pirazzini, Chiara

AU - De Cecco, Marco

AU - Giuliani, Cristina

AU - Lanzarini, Catia

AU - Ravaioli, Francesco

AU - Marasco, Elena

AU - Van Heemst, Diana

AU - Suchiman, H. Eka D

AU - Slieker, Roderick

AU - Giampieri, Enrico

AU - Recchioni, Rina

AU - Marcheselli, Fiorella

AU - Salvioli, Stefano

AU - Vitale, Giovanni

AU - Olivieri, Fabiola

AU - Spijkerman, Annemieke M W

AU - Dollé, Martijn E T

AU - Sedivy, John M.

AU - Castellani, Gastone

AU - Franceschi, Claudio

AU - Slagboom, Pieternella Eline

AU - Garagnani, Paolo

N1 - © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

PY - 2017/8

Y1 - 2017/8

N2 - Epigenetic remodeling is one of the major features of the aging process. We recently demonstrated that DNA methylation of ELOVL2 and FHL2 CpG islands is highly correlated with age in whole blood. Here we investigated several aspects of age-associated hypermethylation of ELOVL2 and FHL2 We showed that ELOVL2 methylation is significantly different in primary dermal fibroblast cultures from donors of different ages. Using epigenomic data from public resources, we demonstrated that most of the tissues show ELOVL2 and FHL2 hypermethylation with age. Interestingly, ELOVL2 hypermethylation was not found in tissues with very low replication rate. We demonstrated that ELOVL2 hypermethylation is associated with in vitro cell replication rather than with senescence. We confirmed intra-individual hypermethylation of ELOVL2 and FHL2 in longitudinally assessed participants from the Doetinchem Cohort Study. Finally we showed that, although the methylation of the two loci is not associated with longevity/mortality in the Leiden Longevity Study, ELOVL2 methylation is associated with cytomegalovirus status in nonagenarians, which could be informative of a higher number of replication events in a fraction of whole-blood cells. Collectively, these results indicate that ELOVL2 methylation is a marker of cell divisions occurring during human aging.

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