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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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Abbreviations

cAge:

Calendar age

DNAmAge:

DNA methylome age

FACS:

Fluorescence-activated cell sorting analysis

MAD:

The median of the differences between DNAmAge and cAge

PBMC:

Peripheral blood mononuclear cell

PCA:

Principal component analysis

WBL:

White blood leukocyte

YFS:

Young Finns study

V90:

Vitality 90+ study

Δ-cAge-DNAmAge:

The difference between calendar age and DNA methylome age

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Acknowledgments

The YFS has been financially supported by the Academy of Finland (grants 286284 (T.L), 132704 (M.H.), 134309 (Eye), 126925, 121584, 124282, 129378 (Salve), 117787 (Gendi), 41071 (Skidi) and 250602 (Coctel to M.J.); the Social Insurance Institution of Finland; Kuopio, Tampere and Turku University Hospital Medical Funds (grant X51001 for T.L.); the Juho Vainio Foundation; the Paavo Nurmi Foundation; the Finnish Foundation of Cardiovascular Research (T.L.); the Tampere Tuberculosis Foundation (T.L., M.H., I.J.); the Emil Aaltonen Foundation (T.L., L.Ku.); the Finnish Cultural Foundation, Pirkanmaa Regional fund (N.M); and the Yrjö Jahnsson Foundation (T.L., M.H.) This work was also supported by grants from the Competitive Research Fund of Pirkanmaa Hospital District (9M017, 9N013 to M.H. and 9P002 to M.J.), Sigrid Juselius Foundation (I.J.), Finnish Medical Association (I.J.) and Competitive Research Fund of Fimlab Laboratories (X51409, I.J.). We thank Nina Peltonen, Sinikka Repo-Koskinen, Eeva Timonen, Janette Hinkka and Kristiina Lehtinen for their excellent technical assistance.

Authors’ contributions

LK processed the data, performed the analyses and was responsible for writing the manuscript. LK, SM, JJ, LKu, NM and TN were responsible for performing the experiments. MH, MK, IJ and TL provided reagents and materials. LK, SM, TL, JJ and MH contributed to the design of the study. MH, MJ, AH, OTR, MK and TL were responsible for recruiting the subjects for the study. All authors contributed to the writing of the manuscript and read and approved the final manuscript.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, School of Medicine, University of Tampere, Tampere, Finland

    L. Kananen, S. Marttila, T. Nevalainen, M. Hurme & J. Jylhävä

  2. Gerontology Research Center, Tampere, Finland

    L. Kananen, S. Marttila, T. Nevalainen, A. Hervonen, M. Jylhä, M. Hurme & J. Jylhävä

  3. School of Medicine, University of Tampere, Tampere, Finland

    L. Kummola & I. Junttila

  4. Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland

    I. Junttila, N. Mononen, T. Lehtimäki & M. Hurme

  5. Department of Clinical Physiology, Tampere University Hospital and University of Tampere School of Medicine, Tampere, Finland

    M. Kähönen

  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

    O. T. Raitakari

  7. School of Health Sciences, University of Tampere, Tampere, Finland

    A. Hervonen & M. Jylhä

  8. Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere, Finland

    T. Lehtimäki

Authors
  1. L. Kananen
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  2. S. Marttila
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  3. T. Nevalainen
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  4. L. Kummola
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  6. N. Mononen
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  7. M. Kähönen
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  8. O. T. Raitakari
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  10. M. Jylhä
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Corresponding author

Correspondence to L. Kananen.

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Electronic supplementary material

Additional file 1

Supporting data of this manuscript (DNAmAges and other fenotypes) (XLSX 90 kb)

Additional file 2

More detailed summary information of the DNAmAges (PDF 354 kb)

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Kananen, L., Marttila, S., Nevalainen, T. et al. The trajectory of the blood DNA methylome ageing rate is largely set before adulthood: evidence from two longitudinal studies. AGE 38, 65 (2016). https://doi.org/10.1007/s11357-016-9927-9

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