# DNA methylation differences underlying female reproductive aging

> **NIH NIH K01** · EMORY UNIVERSITY · 2024 · $102,555

## Abstract

PROJECT SUMMARY
Reproductive aging occurs earlier than systemic aging as a person with ovaries’ ovarian reserve is depleted as
they approaches menopause. There is considerable variability around when a person with ovaries reaches
menopause, yet few contributing factors have been identified. Assessment of reproductive age involves
measuring ovarian reserve and oocyte function, which has clearly-defined parameters in in vitro fertilization.
As ovarian reserve declines, Anti-Mullerian hormone levels fall and women produce fewer oocytes after
ovarian stimulation. Oocyte function also declines, as fewer mature oocytes are produced and have the
capacity to be fertilized. The mechanisms of these age-related declines are unclear, but may involve changes
in DNA methylation, which are known to occur with age and may reflect the biological processes underlying
reproductive aging. We hypothesize that DNA methylation patterns will be associated with ovarian reserve and
oocyte function, and that people with ovaries with poor ovarian reserve and oocyte function will experience
epigenetic age acceleration and will accumulate more stochastic epigenetic mutations. To test this hypothesis,
we will first perform an epigenome-wide association to examine DNA methylation patterns associated with
each measure of ovarian reserve and oocyte function. Then, we will calculate epigenetic age and age
acceleration, which are indicators of biological aging, and stochastic epigenetic mutations, which increase with
age and may disrupt key biological pathways in an individual. If successful, this proposal will provide a better
understanding of the genes and processes associated with reproductive aging, would allow for future
development of targeted treatments to slow or reverse aging, and would help identify women at increased risk
of chronic disease later in life. This proposal will provide focused training opportunities that will be crucial for
my success as an independent, NIH-funded researcher. I will work with experts in the fields of aging biology
and reproductive aging, epigenetic aging, and clinical and translational research. Finally, I will seek additional
training in grant and manuscript writing. This training will position me to apply for future R01 funding and
become an independent investigator.

## Key facts

- **NIH application ID:** 10833670
- **Project number:** 5K01AG078497-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Anna Kaitlyn Knight
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $102,555
- **Award type:** 5
- **Project period:** 2023-05-01 → 2024-12-05

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10833670

## Citation

> US National Institutes of Health, RePORTER application 10833670, DNA methylation differences underlying female reproductive aging (5K01AG078497-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10833670. Licensed CC0.

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