The trajectory of the blood DNA methylome ageing rate is largely set before adulthood: evidence from two longitudinal studies.
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.
Department of Microbiology and Immunology, School of Medicine, University of Tampere, Tampere, Finland. laura.kananen@uta.fi.|Gerontology Research Center, Tampere, Finland. laura.kananen@uta.fi.
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Kananen
Department of Microbiology and Immunology, School of Medicine, University of Tampere, Tampere, Finland.|Gerontology Research Center, Tampere, Finland.
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Marttila
Department of Microbiology and Immunology, School of Medicine, University of Tampere, Tampere, Finland.|Gerontology Research Center, Tampere, Finland.
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Nevalainen
School of Medicine, University of Tampere, Tampere, Finland.
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L
Kummola
School of Medicine, University of Tampere, Tampere, Finland.|Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland.
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Junttila
Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland.
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N
Mononen
Department of Clinical Physiology, Tampere University Hospital and University of Tampere School of Medicine, Tampere, Finland.
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Kähönen
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.
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Raitakari
Gerontology Research Center, Tampere, Finland.|School of Health Sciences, University of Tampere, Tampere, Finland.
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A
Hervonen
Gerontology Research Center, Tampere, Finland.|School of Health Sciences, University of Tampere, Tampere, Finland.
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M
Jylhä
Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland.|Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere, Finland.
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Lehtimäki
Department of Microbiology and Immunology, School of Medicine, University of Tampere, Tampere, Finland.|Gerontology Research Center, Tampere, Finland.|Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland.
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M
Hurme
Department of Microbiology and Immunology, School of Medicine, University of Tampere, Tampere, Finland.|Gerontology Research Center, Tampere, Finland.
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Jylhävä
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D004247:DNA / Q000097:blood*; D004249:DNA Damage; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D055815:Young Adult
D015415:Biomarkers; D004247:DNA
DNA methylation; DNAmAge; Epigenetic clock; Follow-up; Immunosenescence