Accelerated biological aging six decades after prenatal famine exposure

Abstract

AbstractTo test the hypothesis that early-life adversity accelerates the pace of biological aging, we analyzed data from the Dutch Hunger Winter Families Study (DHWFS, N=951). DHWFS is a natural-experiment birth-cohort study of survivors of in-utero exposure to famine conditions caused by the German occupation of the Western Netherlands in Winter 1944-5, matched controls, and their siblings. We conducted DNA methylation analysis of blood samples collected when the survivors were aged 58 to quantify biological aging using the DunedinPACE, GrimAge, and PhenoAge epigenetic clocks. Famine survivors had faster DunedinPACE, as compared with controls. This effect was strongest among women. Results were similar for GrimAge, although effect-sizes were smaller. We observed no differences in PhenoAge between survivors and controls. Famine effects were not accounted for by blood-cell composition and were similar for individuals exposed early and later in gestation. Findings suggest in-utero undernutrition may accelerate biological aging in later life.Significance StatementEnvironmental conditions during gestation are hypothesized to shape health across the life course. The Dutch Hunger Winter, a famine caused by a German blockade of the Western Netherlands in late 1944 and ended by the allied liberation of the Netherlands in Spring 1945, has been studied as a “natural experiment” in which the timing of a child’s conception determined their exposure to severe under-nutrition during gestation. We applied this natural-experiment design to test effects of in-utero adversity on midlife biological aging, as measured by epigenetic clocks. We found that individuals with in-utero famine exposure had a faster pace of biological aging six decades later. The environmental conditions surrounding pregnancy have potential to shape aging trajectories for the next generation.