Malnutrition in the womb accelerates biological aging processes

A study from 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 utero show signs of accelerated aging six decades later. The effects of famine were consistently greater in women and virtually nonexistent in men. The results are 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 initiated by a food embargo imposed by the occupying German forces in early October 1944. During this period, food in the affected regions of the Netherlands was rationed. The researchers used dietary records to determine the period of famine when average daily food intake fell below 900 kcal.

Biological aging is thought to occur due to 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 several famines that people exposed to famine in utero can develop health problems later," explained Mengling Cheng, 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 the Columbia Center on Aging. "Our goal in this study was to test the hypothesis that this increased risk may be associated with accelerated biological aging."

"Famine research can be a powerful tool for understanding how trauma that occurs very early in life affects our health and development," said Daniel Belsky, associate professor of epidemiology in the Center on Aging, Cheng's research fellowship host, and senior author. Research. "In this study, we used fasting as a kind of 'natural experiment' to explore how nutritional disruption and stress during fetal development can affect the biological processes of aging many decades later."

The accelerated aging observed by researchers in famine survivors has been associated in other studies with shorter life spans and earlier onset of cardiovascular disease, stroke, dementia and physical disability. "Our findings suggest that these survivors may be on the path to shorter, healthier lives," Belsky said.

The researchers analyzed data from the Dutch Winter Hungry Family Study (DHWFS), a naturalistic experimental birth cohort study of 951 survivors of in-utero exposure to famine. They examined changes in DNA methylation - or chemical marks on DNA that regulate gene expression and change with age. These algorithms are often called "epigenetic clocks."

Based on blood samples collected when survivors were 58 years old, the researchers assessed biological aging using the DunedinPACE tool developed by Belsky and colleagues at Duke and Otago universities in New Zealand. The watch measures how quickly a person's body breaks down as they age, "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 951 cohort participants included 487 famine survivors with available DNA data, 159 time controls, and 305 sibling controls. Temporary controls were born before or after the famine in the same hospitals as the famine survivors, and they also had sisters or brothers of the same sex.

Comparisons were made with non-famine controls on three measures of DNA biological aging at each of six time points, from preconception to late pregnancy. In addition, the full cohort sample was interviewed and almost all participated in a clinical examination during DNA collection.

"Although 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 aging processes," said Belski.

“In fact, we consider our estimates of hunger to be conservative,” noted L.Kh. Lumay, a professor of epidemiology at Columbia University School of Medicine and founder of the Dutch Hunger Winter Families Study, in which the study was conducted. Lumay conducted a number of studies among cohorts exposed to famine in the Netherlands, Ukraine and China.

"The extent to which observed differences in measures of biological aging will lead to further differences in life expectancy and quality of life remains to be determined. Continued mortality surveillance of this cohort will therefore be necessary as survivors of in utero exposure to famine approach their ninth decade of life."