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Malnutrition in utero accelerates biological aging processes
Last reviewed: 02.07.2025
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A study conducted at Columbia University School of Medicine and the Robert N. Butler Center on Aging at Columbia University found that children born after exposure to famine in the womb show signs of accelerated aging six decades later. The effects of famine were consistently greater in women and virtually nonexistent in men. The results were published in the journal Proceedings of the National Academy of Sciences.
The Dutch famine, which occurred between November 1944 and May 1945, during the German surrender in World War II, was triggered by a food embargo imposed by the occupying German forces in early October 1944. During this period, food was rationed in the affected regions of the Netherlands. Researchers used ration records to determine the period of famine when average daily food consumption fell below 900 kcal.
Biological aging is thought to arise from the accumulation of changes at the cellular level that gradually undermine the resilience of cells, tissues, and organs, directly influencing how quickly people lose function and develop disease as they age.
"We know from previous studies of multiple famines that people exposed to famine in the womb may develop health problems later in life," said Mengling Chen, lead author of the study and a Marie Curie Fellow at the University of Lausanne who worked on the project during a research stay at Columbia's Center on Aging. "Our goal in this study was to test the hypothesis that this increased risk may be related to accelerated biological aging."
"Famine research can be a powerful tool for understanding how traumas that occur very early in life affect our health and development," said Daniel Belsky, an associate professor of epidemiology at the Center on Aging, Cheng's research tenure, and the study's senior author. "In this study, we used famine as a kind of 'natural experiment' to explore how disruptions to nutrition and stress during fetal development can affect the biological processes of aging many decades later."
The accelerated aging that the researchers documented in famine survivors has been associated in other studies with shorter life spans and earlier onset of heart disease, stroke, dementia and physical disability. "Our findings suggest that these survivors may be on track to shorter healthy life spans," Belsky said.
The researchers analyzed data from the Dutch Hunger Winter Family Study (DHWFS), a naturalistic birth cohort study of 951 survivors of famine exposure in the womb. They looked at changes in DNA methylation — or chemical marks on DNA that regulate gene expression — that change with age. These patterns are often called the “epigenetic clock.”
Based on blood samples collected when the survivors were 58 years old, the researchers assessed biological aging using a tool called DunedinPACE, developed by Belsky and colleagues at Duke and Otago universities in New Zealand. The clock measures how quickly a person’s body deteriorates as it ages, “like a speedometer for the biological processes of aging,” Belsky explained. For comparison, Belsky and colleagues also analyzed two other epigenetic clocks, GrimAge and PhenoAge.
Famine survivors had faster DunedinPACE compared to controls. This effect was most pronounced in women, while it had virtually no effect on the rate of aging in the men studied.
Data for the 951 cohort participants included 487 famine survivors with available DNA data, 159 time-matched controls, and 305 control siblings. Time-matched controls were born before or after the famine in the same hospitals as the famine survivors and also had sisters or brothers of the same sex.
Comparisons were made with unfed controls on three measures of DNA-biological aging at each of six time points, from preconception to the end of pregnancy. In addition, the full cohort sample was interviewed, and nearly all participated in a clinical examination at the time of DNA collection.
"While there is no gold standard for measuring biological aging, the overall consistency of results across three different epigenetic biological aging clocks developed in different cohorts using different endpoints strengthens confidence that our results truly reflect the aging process," Belsky said.
"We actually think our famine estimates are conservative," said L.H. Lumay, a professor of epidemiology at Columbia University School of Medicine and founder of the Dutch Hunger Winter Family Study, which conducted the study. Lumay has conducted a number of studies of famine-affected cohorts in the Netherlands, Ukraine and China.
"The extent to which observed differences in measures of biological aging will translate into further differences in life expectancy and quality of life remains to be determined. Therefore, continued mortality monitoring of this cohort is necessary as survivors of in utero famine approach their ninth decade of life."