Aging of the female reproductive tract occurs earlier than other tissues and has broad implications for women’s health, yet the lower female genital tract remains poorly characterized due to challenges in sampling. Here, we evaluated whether cervicovaginal fluid (CVF), collected using self-inserted menstrual discs, can provide insight into reproductive aging. CVF samples were collected from 20 women aged 20–69 years and analyzed using bulk transcriptomics, flow cytometric immune phenotyping, 16S rRNA sequencing of the vaginal microbiome, and DNA methylation profiling with data from matched whole blood. CVF showed accelerated epigenetic aging relative to chronological and blood-based epigenetic age in multiple epigenetic clocks. Age was further associated with DNA methylation and transcriptional signatures consistent with immune activation, shifts toward innate immune pathways, and altered tissue remodeling. Microbiome analyses demonstrated increased community diversity and reducedLactobacillus dominance with age. Together, these findings demonstrate that CVFcan be obtained via non-invasive sampling and shows coordinated epigenetic,immune, and microbial signatures of reproductive aging, establishing a framework for studying sex specific aging biology and health across the lifespan.
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Please direct any questions/requests to Eric Schafer: eeschafer@medicine.wisc.edu
