# Sex Hormones, Aging, Alzheimer's Disease and Other Neurodegenerative Diseases in Women

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $79,371

## Abstract

Abstract
As the general population ages, understanding the factors that contribute to longevity, healthy aging, and
disability is paramount. Sex hormones (SH) have been hypothesized to be one of the possible reasons for the
gender difference in both longevity and neurodegenerative disorders (ND).13 SH, specifically estrogen,
progesterone and testosterone) have shown neuroprotective effects in animal and cell-line studies,14–16 and in
disease-related animal models for Alzheimer’s Disease,17–24 Parkinson’s Disease,25–29 and Huntington’s
Disease.30–35 Previous studies analyzing the effect of sex hormones (reproductive history or hormone
metabolizing genes) on ND and longevity in human observational studies have been inconclusive. 36–104 Also
inconsistent have been the clinical trials that analyzed whether postmenopausal hormone therapy had a
positive effect on ND.105–113 Hence, the role of SH on longevity and ND remain elusive.
 The goal of this project is to analyze the association between sex hormones and epigenetic aging and age-
related neurodegenerative diseases. The project is divided into three aims. In the first aim, three different
methods to predict SH levels will be created using whole genome genetics, large-scale methylation data, and
questionnaire-based information. In the second aim, both measured SH and SH predictive scores will be
associated with epigenetic age. Epigenetic age is known to be strongly associated with mortality and therefore,
is a robust measure to estimate longevity.114,115 In the third aim, the development of ND (Alzheimer’s disease
and Parkinson’s disease), as well as age of onset (Alzheimer’s disease, Parkinson’s disease and Huntington’s
disease), will be associated with the SH predictive scores based on the first aim. Finally, assuming an
association was identified in aims 2 and 3, mediation analysis will be performed as a potential sub-aim to
analyze whether epigenetic aging can partially explain the association between sex hormones and ND. To
ensure statistical power and the ability to verify and replicate the findings, several large observational datasets
will be used. These studies and approaches will address the role of sex hormones from various angles, and
will help to triangulate evidence and inform future research into potential therapeutic targets.
 With training from, and collaborations with several experts in genetic, epigenetic, and epidemiological
analyses, the applicant will gain expertise to unlock some of these questions and contribute to aging and
neurodegenerative disease-related discoveries. Maximizing an interdisciplinary approach, incorporating
genetics, epigenetics, epidemiology, biostatistics and neurology considerations, will generate a broad range of
independent research.

## Key facts

- **NIH application ID:** 10088326
- **Project number:** 5F32AG063442-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Cynthia Diana Johanna Kusters
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $79,371
- **Award type:** 5
- **Project period:** 2019-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10088326

## Citation

> US National Institutes of Health, RePORTER application 10088326, Sex Hormones, Aging, Alzheimer's Disease and Other Neurodegenerative Diseases in Women (5F32AG063442-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10088326. Licensed CC0.

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