The age at which women reach puberty or give birth may have profound consequences for their long-term health. New research published in eLife by investigators at the Buck Institute shows that girls who experience puberty (marked by the onset of menstruation) before age 11 or women who have their first child before age 21 face significantly elevated health risks. Specifically, these women are twice as likely to develop type 2 diabetes, obesity, and heart failure, and four times more likely to suffer from severe metabolic disorders later in life. Conversely, later puberty and childbirth were genetically linked to longer lifespan, reduced frailty, slower epigenetic ageing, and a lower risk of age-related conditions such as diabetes and Alzheimer’s disease.
Buck professor Dr Pankaj Kapahi, senior author of the study, underscores the public health importance of these findings. “Although menstrual and childbirth history is routinely recorded during medical care, it is rarely considered outside of gynaecological contexts,” he explains. “Our research shows that these factors, whether beneficial or harmful, have a powerful influence on ageing and the development of disease. They need to be incorporated into the broader framework of women’s healthcare.”
The study represents one of the most comprehensive analyses of reproductive timing to date. Drawing on regression analyses of nearly 200,000 women enrolled in the UK Biobank, the team identified 126 genetic markers that connect early reproductive events with accelerated ageing. “Many of these markers lie within well-known longevity pathways, including IGF-1, growth hormone, AMPK, and mTOR signalling,” notes Dr Yifan Xiang, a postdoctoral fellow who led the research. These pathways regulate metabolism and ageing, making them central to understanding how early puberty and childbirth set the stage for long-term health risks.
The findings provide compelling evidence for the evolutionary concept of antagonistic pleiotropy—the idea that genetic traits advantageous early in life can have damaging consequences later on. “Our results show that genetic factors promoting early reproduction carry a substantial cost for women as they age,” Kapahi says. “From an evolutionary perspective, it makes sense: traits that enhance the survival of offspring may simultaneously increase disease risk and accelerate ageing in the mother.”
Body Mass Index (BMI) emerged as a key mechanism in this process. The study demonstrated that women who undergo early reproductive events tend to have higher BMI, which in turn increases their risk for metabolic diseases. Kapahi elaborates: “Enhanced nutrient absorption would be advantageous in the context of supporting offspring survival, but in today’s world of abundant calories, this same mechanism contributes to obesity and diabetes.”
From a public health standpoint, the implications are far-reaching. Kapahi argues that integrating reproductive timing into healthcare strategies could improve health outcomes across the lifespan. Personalised approaches—including lifestyle interventions, routine metabolic screenings, and targeted nutritional guidance—may help offset the risks linked to early puberty and early childbirth. The issue is especially timely, as recent research shows that the age of menarche in the United States has steadily declined by about three months per decade since the 1970s. While the underlying causes remain uncertain, rising rates of childhood obesity appear to play a role.
Finally, the study challenges long-standing practices in basic science research. Most preclinical studies on ageing use virgin female mice, which may not adequately represent the health trajectories of women who reproduce early. Kapahi suggests this oversight limits the translational value of such research. “If evolution has prioritised early reproduction at the expense of healthy ageing, then we need to ask how this knowledge can be applied in modern society,” he reflects. “We cannot alter our genetic inheritance, but we can use these insights to shape lifestyle, healthcare, and even medical interventions aimed at extending women’s healthspan.” The identification of genetic pathways associated with reproductive timing, he adds, also opens avenues for future therapies that could benefit both mothers and their children.
More information: Yifan Xiang et al, Early menarche and childbirth accelerate aging-related outcomes and age-related diseases: Evidence for antagonistic pleiotropy in humans, eLife. DOI: 10.7554/eLife.102447.4
Journal information: eLife Provided by Buck Institute for Research on Aging
