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      The trajectory of the blood DNA methylome ageing rate is largely set before adulthood: evidence from two longitudinal studies

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          Abstract

          The epigenetic clock, defined as the DNA methylome age (DNAmAge), is a candidate biomarker of ageing. In this study, we aimed to characterize the behaviour of this marker during the human lifespan in more detail using two follow-up cohorts (the Young Finns study, calendar age i.e. cAge range at baseline 15–24 years, 25-year-follow-up, N = 183; The Vitality 90+ study, cAge range at baseline 19–90 years, 4-year-follow-up, N = 48). We also aimed to assess the relationship between DNAmAge estimate and the blood cell distributions, as both of these measures are known to change as a function of age. The subjects’ DNAmAges were determined using Horvath’s calculator of epigenetic cAge. The estimate of the DNA methylome age acceleration (Δ-cAge-DNAmAge) demonstrated remarkable stability in both cohorts: the individual rank orders of the DNAmAges remained largely unchanged during the follow-ups. The blood cell distributions also demonstrated significant intra-individual correlation between the baseline and follow-up time points. Interestingly, the immunosenescence-associated features (CD8+CD28− and CD4+CD28− cell proportions and the CD4/CD8 cell ratio) were tightly associated with the estimate of the DNA methylome age. In summary, our data demonstrate that the general level of Δ-cAge-DNAmAge is fixed before adulthood and appears to be quite stationary thereafter, even in the oldest-old ages. Moreover, the blood DNAmAge estimate seems to be tightly associated with ageing-associated shifts in blood cell composition, especially with those that are the hallmarks of immunosenescence. Overall, these observations contribute to the understanding of the longitudinal aspects of the DNAmAge estimate.

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          The online version of this article (doi:10.1007/s11357-016-9927-9) contains supplementary material, which is available to authorized users.

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          Author and article information

          Contributors
          laura.kananen@uta.fi
          Journal
          Age (Dordr)
          Age
          Springer International Publishing (Cham )
          0161-9152
          1574-4647
          14 June 2016
          June 2016
          : 38
          : 3
          : 65
          Affiliations
          [1 ]Department of Microbiology and Immunology, School of Medicine, University of Tampere, Tampere, Finland
          [2 ]Gerontology Research Center, Tampere, Finland
          [3 ]School of Medicine, University of Tampere, Tampere, Finland
          [4 ]Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland
          [5 ]Department of Clinical Physiology, Tampere University Hospital and University of Tampere School of Medicine, Tampere, Finland
          [6 ]Research Centre of Applied and Preventive Cardiovascular Medicine and the Department of Clinical Physiology and Nuclear Medicine, University of Turku and Turku University Hospital, Turku, Finland
          [7 ]School of Health Sciences, University of Tampere, Tampere, Finland
          [8 ]Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere, Finland
          Article
          PMC5005919 PMC5005919 5005919 9927
          10.1007/s11357-016-9927-9
          5005919
          27300324
          4a88c032-870e-4187-8b8d-548f0266e37e
          © American Aging Association 2016
          History
          : 19 November 2015
          : 31 May 2016
          Funding
          Funded by: FundRef http://dx.doi.org/10.13039/501100002341, Suomen Akatemia;
          Award ID: 286284(to TL), 132704(to MH), 134309 (Eye), 126925, 121584, 124282, 129378(Salve), 117787(Gendi), 41071 (Skidi), 250602 (Coctel to MJ)
          Funded by: Social insurance Institution of Finland
          Funded by: Kuopio, Tampere and Turku University Hospital Medical Funds
          Award ID: X51001
          Funded by: FundRef http://dx.doi.org/10.13039/501100004037, Juho Vainion Säätiö (FI);
          Funded by: Paavo Nurmi Säätiö (FI)
          Funded by: FundRef http://dx.doi.org/10.13039/501100005633, Sydäntutkimussäätiö;
          Funded by: FundRef http://dx.doi.org/10.13039/501100006706, Tampereen TuberkuloosisäätiÖ;
          Award ID: to TL, MH and IJ
          Funded by: FundRef http://dx.doi.org/10.13039/501100004756, Emil Aaltosen Säätiö;
          Award ID: to TL and LKu
          Funded by: FundRef http://dx.doi.org/10.13039/501100005431, Pirkanmaan Rahasto;
          Funded by: Yrjö Jahnsson Säätiö (FI)
          Award ID: to TL and MH
          Funded by: Competitive Research Fund of Pirkanmaa Hospital District
          Award ID: 9M017, 9N013 to MH; 9P002 to MJ
          Funded by: FundRef http://dx.doi.org/10.13039/501100006306, Sigrid Juséliuksen Säätiö;
          Funded by: FundRef http://dx.doi.org/10.13039/100008723, Suomen Lääketieteen Säätiö;
          Funded by: Competitive Research Fund of Fimlab Laboratories
          Award ID: X51409
          Categories
          Article
          Custom metadata
          © American Aging Association 2016

          DNA methylation,DNAmAge,Epigenetic clock,Follow-up,Immunosenescence

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