Swiss Centre of Expertise in Life Course Research, Faculty of Social and Political Sciences, University of Lausanne, Lausanne CH 1015, Switzerland.
Robert N. Butler Columbia Aging Center, Mailman School of Public Health, Columbia University, New York, NY 10032.
Proc Natl Acad Sci U S A. 2024 Jun 11;121(24):e2319179121. doi: 10.1073/pnas.2319179121. Epub 2024 Jun 4.
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 to 1945, 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.
为了验证早期逆境加速生物衰老速度的假设，我们分析了荷兰饥荒家庭研究（DHWFS，N=951）的数据。DHWFS 是一项自然实验性出生队列研究，研究对象为在 1944 年至 1945 年冬季德国占领荷兰西部期间，子宫内暴露于饥饿条件下的幸存者、匹配的对照者及其兄弟姐妹。我们对幸存者在 58 岁时采集的血液样本进行了 DNA 甲基化分析，使用 DunedinPACE、GrimAge 和 PhenoAge 表观遗传时钟来量化生物衰老。与对照组相比，饥荒幸存者的 DunedinPACE 更快。这种影响在女性中最为明显。对于 GrimAge，结果相似，尽管效应大小较小。我们在幸存者和对照组之间没有观察到 PhenoAge 的差异。饥荒的影响与血细胞组成无关，且在妊娠早期和晚期暴露的个体中相似。这些发现表明子宫内营养不良可能会加速晚年的生物衰老。
