Pregnancy is a wonder of biology, but new research shows that feat may come at a price. In a study published in Proceedings of the National Academy of Sciences, scientists found that women who have been pregnant showed more signs of biological aging compared to women who had never been pregnant before. The more times a woman had been pregnant, the faster her rate of biological aging.
“We’re learning that pregnancy has long-term effects on the body,” says Calen Ryan, associate research scientist at the Columbia University Aging Center at the Mailman School of Public Health. “They are not all bad, but it seems to increase the risk of some diseases and all-cause mortality.”
The study
Ryan and his team analyzed data from more than 1,700 people in the Philippines who were part of the Cebu Longitudinal Health and Nutrition Survey. The participants, who were all ages 20 to 22 back in 2005 when the study began, provided blood samples and answered questions about their reproductive and sexual history, including how many times they had been pregnant and whether or not those pregnancies had resulted in live births. A smaller group of women provided additional blood samples from 2009 to 2014 to let researchers compare changes over time.
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All of the blood samples were analyzed for a number of biological factors associated with aging, including changes in DNA known as epigenetic modifications. As cells age, they accumulate molecular imprints of which genes have been turned on or off, and these changes can serve as a proxy for how biologically old the cells are. These so-called "epigenetic clocks" can also capture the effects of things such as stress and other physiological and psychological experiences that impact cells, and therefore make the cells either “older” or “younger” than their chronological age.
What they found
Ryan and his team used six such epigenetic clocks, which assessed 19 different indicators including changes to the length of chromosomes (which shorten the more a cell divides), to assess the participants’ ages. They found that overall, women who had been pregnant at least once were biologically older than women of the same age who had not been pregnant. Pregnancy led to anywhere from four months to more than a year of faster aging, at a rate of about 3% more per year than women who had never been pregnant.
The researchers then looked at how being pregnant more than once might affect measures of aging. Women with more pregnancies aged up to five months faster compared to women with fewer pregnancies, or an acceleration of the pace of aging by nearly 2% a year per pregnancy.
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Those measures looked at the women as a whole, so changes could have been due to more dramatic changes in some women compared to others. To zoom in on the effects of pregnancy, Ryan then focused on a smaller group of women and compared each woman’s epigenetic clock results at the start of the study to those up to nine years later. These results were more mixed, and women who had been pregnant more times showed more changes on only two of the epigenetic clocks, compared to women with fewer pregnancies.
Finally, as a type of control to ensure that they accounted for other factors that could affect aging—such as exposure to air pollution, smoking, and socioeconomic status—the group used the same six epigenetic clocks on the men in the study. They found that the number of children the men fathered had no association to the pace of their biological aging.
“It seems there is something about pregnancy as young women in the Philippines that affects biological aging,” says Ryan.
How pregnancy could age the body
There is still a lot more to learn about the association between pregnancy and aging. One explanation for the connection could involve the idea that pregnancy takes a major physical toll on the body, in terms of energy and resources. “The idea is that the body performs certain functions, but is always constrained about optimizing any one of those functions, and it creates a tradeoff,” says Ryan. “So energy going toward reproductive function may draw away from maintenance of the body.”
It’s also unclear how much of this tradeoff is dynamic, or even reversible. In another recent paper, researchers led by Kieran O’Donnell at Yale School of Medicine reported in Cell Metabolism that while they found similar acceleration in aging factors during pregnancy, they also saw encouraging signs that those changes reversed after pregnancy, especially when mothers breastfed. In that study, O’Donnell found that pregnancy increased biological age by one to two years, but that the pace of aging had decreased by 16% by three months postpartum. “The reversal in postpartum in terms of the effect size was much greater than the increase in biological age found during pregnancy,” he says. “That raises the provocative idea that pregnancy may be associated with potential rejuvenation. But we simply can’t answer that question for sure with the data we have so far.”
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Ryan is among those eager to see additional data on the reversal question, which has implications for the millions of women who get pregnant every year. He emphasizes that his results do not definitively conclude that pregnancy makes women age faster. “We have evidence that pregnancy can speed up biological aging,” he says. “And we have evidence that there is recovery after pregnancy. What we don’t know precisely is how much of that recovery compensates for pregnancy, and how much it varies from person to person, or from country to country.”
Ryan, for example, did not include breastfeeding in his analysis but plans to do so in further studies. He also hopes to study the long-term effects of pregnancy over time; since his study included only younger women, it’s not clear how pregnancy affects disease and mortality later in life. He says researchers are only beginning to unlock the power of epigenetic studies, and that deeper understanding of how the body age—and what factors impact that process—are on the way. “Now the floodgates are opening on epigenetics,” he says.
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