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Female reproductive aging shows distinct organ patterns, with the uterus undergoing a significant shift around menopause. This study reveals menopause as a critical turning point in women's aging and overall health.

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Area of Science:

  • Reproductive biology
  • Gerontology
  • Genomics

Background:

  • Female reproductive aging has broad health impacts, but its tissue-level mechanisms are unclear.
  • Understanding organ-specific aging is crucial for addressing late-life health concerns.

Purpose of the Study:

  • To investigate tissue-level aging dynamics across female reproductive organs.
  • To identify molecular and morphological changes associated with aging and menopause.

Main Methods:

  • Integrated deep learning on 1,112 histology images and RNA sequencing from 659 samples across seven reproductive organs.
  • Analyzed plasma proteomics data from a large cohort to validate findings.
  • Utilized multi-omics factor analysis to link histological and gene-expression changes.

Main Results:

  • Discovered asynchronous aging trajectories: gradual ovarian aging versus abrupt uterine shifts around menopause.
  • Identified myometrium as highly age-affected, with extracellular matrix remodeling and immune activation.
  • Observed coordinated epithelial remodeling, including a sharp menopausal transition in the vaginal epithelium.
  • Linked histological changes to nonlinear gene expression shifts impacting reproductive traits like pelvic organ prolapse.

Conclusions:

  • Menopause represents a key inflection point in female aging.
  • Established a tissue-resolved, multi-dataset framework for studying female aging and late-life health.