IN A NEW epigenetic analysis spanning women undergoing in vitro fertilization or elective oocyte cryopreservation, researchers report that DNA-methylation patterns in granulosa cells, the somatic cells that support oocyte development, may reveal both reproductive aging and future systemic health risks. The findings suggest that diminished ovarian reserve may reflect broader biological aging processes rather than reproductive aging alone.
Epigenetic Aging Signals in the Ovary
Using the DunedinPACE molecular clock, the team assessed the “pace of aging” within granulosa cell DNA obtained from follicular fluid. After adjusting for age and BMI, higher DunedinPACE values, indicating faster biological aging, were consistently associated with lower antimüllerian hormone (AMH) levels and reduced antral follicle count (AFC). Both measures are standard clinical indicators of ovarian reserve.
Cardiometabolic Risk Embedded in Methylation Profiles
The study further evaluated methylation risk scores (MRS) for cardiovascular disease and metabolic syndrome. Again, lower ovarian reserve markers correlated with higher predicted cardiometabolic risk. Women with diminished AMH or AFC showed increased CVD-MRS and MetS-MRS values, suggesting that ovarian reserve may mirror systemic health vulnerability.
Clinical Correlates During IVF Cycles
Accelerated epigenetic aging and higher MRS scores were also linked to fewer mature follicles at trigger and lower numbers of retrieved oocytes. Although the association between MetS MRS and oocyte yield lost significance after adjustment, the overall pattern reinforced a biologically coherent trend.
Implications for Women’s Health
According to the authors, granulosa cell methylation signatures could eventually serve as biomarkers for early identification of women at elevated long-term health risk. While validation in larger cohorts is required, the work underscores a growing recognition: ovarian reserve may be an early-life indicator of cardiometabolic aging. Early screening and preventive strategies, they write, could meaningfully alter long-term outcomes.
Reference
Herweck AM et al. Prediction of aging pace and health risks by granulosa cell DNA methylation. Fertil Steril. 2025;124(6):1303-13.
