Undernourishment while in the womb may speed aging in adulthood

Scientists have found evidence that adults who had experienced famine while still in the womb aged faster than individuals who did not experience this during gestation. Using data from 951 individuals in the Dutch Hunger Winter Families Study, and measures of DNA methylation from blood samples collected in adulthood, researchers found causal evidence that exposure to famine conditions in utero resulted in epigenetic age acceleration. The study was funded in part by NIA and published in PNAS.

Epigenetic age acceleration refers to the difference between biological age and chronological age. Biological age is the accumulation of damage, including physiological changes and loss of function, that occur in a person's cells over time. One method scientists use to measure biological age is by measuring epigenetic changes, such as DNA methylation from blood, tissue, or saliva samples. Previous research has shown that epigenetic age acceleration is highly predictive of health outcomes and mortality in older adults.

The Dutch Hunger Winter Families Study included 2,417 children born in February and March 1945 whose mothers were exposed to famine conditions caused by the German blockade and occupation of the western portion of the Netherlands from late 1944 to Spring 1945. The study also included 890 controls comprised of children born in 1943 and 1947 who were not exposed to the famine in utero. The result is what scientists refer to as a natural experiment, in which a random event causes two groups of individuals to experience vastly different conditions.

By combining the natural experimental results of the Dutch Hunger Winter Families Study and measures of epigenetic age acceleration, researchers at Columbia University in collaboration with the Leiden University Medical Center, Netherlands, tested a theory that in utero exposures have long-term effects on health and aging. Using DNA methylation to quantify biological aging, the findings showed individuals exposed to famine in utero had aged faster six decades later, with women showing stronger effects than men.

Caveats of the study include that it is limited to one population and that there is currently no standard scientific criteria for measuring biological age. However, results of the study provide further evidence that undernutrition in utero has lasting impacts on later life health. It also builds upon similar work examining in utero exposure to poor economic conditions during the Great Depression of the 1930s in the United States.

This research was supported in part by NIA grants R01AG066887, R01AG042190, and R00AG056599.

Reference: Cheng M, et al. Accelerated biological aging six decades after prenatal famine exposure. Proceedings of the National Academy of Sciences of the United States of America. 2024. Epub June 4. doi: 10.1073/pnas.2319179121.