Menopause Awareness Month is observed every October, a global initiative that aims to increase understanding of menopause, highlight symptoms, and promote supportive resources for those experiencing the transition. This October, a newly published study is shedding light on how reproductive history – particularly menopause timing – relates to biological aging measured by DNA methylation clocks. The study adds to research exploring the relationship between reproductive health and biological aging, raising questions about how these findings may eventually inform women’s health assessment.

Reproductive Health and Aging

A National University of Singapore Medicine-led systematic review and meta-analysis involving more than 550,000 women found that earlier menopause and a higher number of births were associated with modestly greater biological age acceleration, offering new insights into women’s health and healthy longevity. Published in Mechanisms of Ageing and Development, the study brought together evidence from 29 previously published studies to examine whether reproductive milestones, pregnancies, and birth outcomes were associated with biological aging measured using DNA methylation (DNAm) clocks.

“Women’s reproductive history forms an important part of their health across the life course,” observes Andrea Maier, Oon Chiew Seng Professor in Medicine, Healthy Ageing and Dementia Research, corresponding author of the study, and director of the NUS Academy for Healthy Longevity at NUS Medicine. “Our findings suggest that events such as menopause may also provide information about underlying biological aging.”

This does not mean that menopause itself makes a woman age faster, Professor Maier adds, “but it highlights the close relationship between reproductive health and the wider aging process.”

Professor Maier, whose work bridges the fields of longevity, women’s health, and biological aging, is an authority in geroscience and precision geromedicine, with more than 500 peer-reviewed publications. She spoke at A4M’s Global Event in Geneva in 2024. This meta-analysis adds to the conversation about biological age measures and the need for further research.

Age Accelerators

By analyzing chemical changes to human DNA that accumulate over time, DNAm clocks can estimate biological aging and provide an indication of how old the body appears biologically compared with a person’s actual age. With this data, researchers can calculate epigenetic age acceleration (EAA), which reflects whether biological aging appears faster or slower than expected.

The meta-analysis found that each one-year earlier age at menopause was associated with approximately 0.08 years, or about one month, of greater epigenetic age acceleration (EAA) when measured using GrimAge, one of the newer-generation DNA methylation clocks. This analysis included 5,920 women. Similar associations were also found using the Horvath1Age and PhenoAge clocks.

Key findings:

“The differences we observed are modest, and our findings should not be interpreted to mean that having children directly causes accelerated aging,” said Matthew Simonson, Ph.D., first author of the study and a researcher with the NUS Academy for Healthy Longevity. “Rather, they suggest that reproductive experiences may be one of several factors associated with the biological changes that accumulate throughout a woman’s life.”

Expanding Research

The use of biomarkers to better understand aging trajectories is not limited to women’s health. Research into age-related changes in immune cells is also helping scientists investigate how the immune system changes over time and how those changes may relate to healthy aging.

A 2025 study published in Nature Immunology used multimodal profiling to examine immune cells across different tissues and age groups. The researchers identified tissue-specific immune signatures and age-related changes in certain immune-cell populations, offering further insight into the complexity of immune aging.

Together, research into DNAm clocks and immune-cell changes highlights the range of approaches scientists are exploring to better understand biological aging. However, further research is needed to establish how these measures might eventually contribute to personalized approaches to preserving healthspan.

Experts agree that more research is needed before DNAm clocks have established clinical utility for this purpose. The findings of the meta-analysis show associations, not cause and effect; the differences were modest, and factors such as socioeconomic circumstances, BMI, and pre-existing health conditions may also influence the results.

“Biological-age measures could eventually complement existing approaches to understanding women’s health, from reproductive ageing to pregnancy outcomes,” Professor Maier said. “Before that can happen, however, we need larger longitudinal studies that follow women over time and establish what these biological-age differences mean for their future health.”

Concluding Thoughts

The NUS review supports the idea that reproductive health events may provide insights into broader biological changes. While more research is needed and the associations found are modest, the findings add to growing evidence linking reproductive history with biological aging trajectories. Further research may help clarify whether these measures could eventually inform approaches to women’s health and healthy longevity.

Sources:

Earlier menopause Linked to Faster Biological Aging, NUS Medicine Study Finds 

Biological Age Measured by DNA Methylation Clocks and Reproductive History: Systematic Review and Meta-Analysis 

Multimodal Profiling Reveals Tissue-Directed Signatures of Human Immune Cells Altered with Age