Journal
AGE
Volume 38, Issue 3, Pages -Publisher
SPRINGER
DOI: 10.1007/s11357-016-9927-9
Keywords
DNA methylation; DNAmAge; Epigenetic clock; Follow-up; Immunosenescence
Categories
Funding
- Academy of Finland [286284, 132704, 134309, 126925, 121584, 124282, 129378, 117787, 41071, 250602]
- Social Insurance Institution of Finland
- Kuopio, Tampere and Turku University Hospital Medical Funds [X51001]
- Juho Vainio Foundation
- Paavo Nurmi Foundation
- Finnish Foundation of Cardiovascular Research
- Tampere Tuberculosis Foundation
- Emil Aaltonen Foundation
- Finnish Cultural Foundation
- Pirkanmaa Regional fund
- Yrjo Jahnsson Foundation
- Competitive Research Fund of Pirkanmaa Hospital District [9M017, 9N013, 9P002]
- Sigrid Juselius Foundation
- Finnish Medical Association
- Competitive Research Fund of Fimlab Laboratories [X51409]
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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 (Delta-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 intraindividual correlation between the baseline and followup 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 Delta-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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