Abstract
BackgroundEpigenetic clocks have been used to indicate differences in biological states between individuals of same chronological age. However, so far, only few studies have examined epigenetic aging in newborns—especially regarding different gestational or perinatal tissues. In this study, we investigated which birth- and pregnancy-related variables are most important in predicting gestational epigenetic age acceleration or deceleration (i.e., the deviation between gestational epigenetic age estimated from the DNA methylome and chronological gestational age) in chorionic villus, placenta and cord blood tissues from two independent study cohorts (ITU, n = 639 and PREDO, n = 966). We further characterized the correspondence of epigenetic age deviations between these tissues.ResultsAmong the most predictive factors of epigenetic age deviations in single tissues were child sex, birth length, maternal smoking during pregnancy, maternal mental disorders until childbirth, delivery mode and parity. However, the specific factors related to epigenetic age deviation and the direction of association differed across tissues. In individuals with samples available from more than one tissue, relative epigenetic age deviations were not correlated across tissues.ConclusionGestational epigenetic age acceleration or deceleration was not related to more favorable or unfavorable factors in one direction in the investigated tissues, and the relative epigenetic age differed between tissues of the same person. This indicates that epigenetic age deviations associate with distinct, tissue specific, factors during the gestational and perinatal period. Our findings suggest that the epigenetic age of the newborn should be seen as a characteristic of a specific tissue, and less as a general characteristic of the child itself.
Highlights
Epigenetic clocks have been used to indicate differences in biological states between individuals of same chronological age
Performance of epigenetic clocks in the investigated tissues We first evaluated the performance of the two epigenetic clocks for cord blood [20, 21] and for placenta [22, 23] in our sample
The clocks differ in the included CpGs, and only share two CpGs with negative weights, and one CpG with positive weight, respectively
Summary
Epigenetic clocks have been used to indicate differences in biological states between individuals of same chronological age. Applying Knight’s clock, epigenetic age deceleration has been linked to exposure to negative pregnancy environments including insulin-treated gestational diabetes mellitus in a previous pregnancy, maternal history of depression and greater antenatal depressive symptoms, maternal Sjögren’s syndrome and a prenatal adverse environment assessed with the cerebroplacental ratio, as well as negative prospective child outcomes such as early childhood psychiatric problems [24,25,26] These findings, together with the observation that epigenetic age acceleration was related to a lower need of respiratory interventions, led to the hypothesis that gestational epigenetic age deceleration may be related to a lower developmental maturity [27]. It should be noted that it was recently shown that CpGs relevant for epigenetic aging in general were linked to developmental processes [30]
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