Accelerated biological aging six decades after prenatal famine exposure

Mengling Cheng; Dalton Conley; Tom Kuipers; Chihua Li; Calen Ryan; Jazmin Taubert; Shuang Wang; Tian Wang; Jiayi Zhou; Lauren L Schmitz; Elmar W Tobi; Bas Heijmans; L H Lumey; Daniel W Belsky

doi:10.1101/2023.11.03.23298046

Accelerated biological aging six decades after prenatal famine exposure

medRxiv [Preprint]. 2023 Nov 4:2023.11.03.23298046. doi: 10.1101/2023.11.03.23298046.

Authors

Mengling Cheng^{1

2}, Dalton Conley³, Tom Kuipers⁴, Chihua Li^{5

6}, Calen Ryan², Jazmin Taubert⁴, Shuang Wang⁷, Tian Wang⁷, Jiayi Zhou², Lauren L Schmitz⁸, Elmar W Tobi⁴, Bas Heijmans⁴, L H Lumey^{4

6}, Daniel W Belsky^{2

6}

Affiliations

¹ Swiss Centre of Expertise in Life Course Research, University of Lausanne, Lausanne, Switzerland.
² Robert N. Butler Columbia Aging Center, Columbia University, New York, NY, USA.
³ Department of Sociology, Princeton University, Princeton, NJ, USA.
⁴ Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands.
⁵ Institute for Social Research, University of Michigan at Ann Arbor, Ann Arbor, MI, USA.
⁶ Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY, USA.
⁷ Department of Biostatistics, Columbia University Mailman School of Public Health, New York, NY, USA.
⁸ Robert M. La Follette School of Public Affairs, University of Wisconsin-Madison, Madison, WI, USA.

Abstract

To 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.

Keywords: biological aging; early-life adversity; famine/undernutrition; natural experiment; prenatal exposure.

Publication types

Preprint

Abstract

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