# MAE-WEST SCORE Project 3 Animal

> **NIH NIH U54** · CEDARS-SINAI MEDICAL CENTER · 2023 · $576,738

## Abstract

Project Abstract – MAE-WEST SCORE Project 3
Over the course of life, chronic stressors contribute to multi-organ aging and dysfunction and, ultimately, the
development of clinical disease. Sex remains a critical determinant of the nature and pace of aging and ultimately
longevity. Among mammalian species, it is even more clear that females fundamentally age differently from
males. With advancing chronologic age in humans, differences in biological aging between women and men
become even more pronounced, culminating in the female predominance for a number of important morbid
disease conditions, including notably Alzheimer’s disease and related dementias (ADRD), heart failure with
preserved ejection fraction (HFpEF), progressive chronic kidney disease (CKD), and in turn systemic frailty.
Mechanisms underlying the female predominance for these major morbidities remains unknown and are not
explained by variations in sex hormones or survival bias. Our preliminary work supports a central hypothesis that
sexual dimorphism in inflammatory eicosanoid mediators contribute to sex differences in microvascular
dysfunction and, in turn, to sex differences in age-related multi-organ disease, including for ADRD, HFpEF and
CKD. Elucidating a common pathophysiologic basis for the female predominance of ADRD, HFpEF, and CKD
holds the key to effective interventions for reducing the excess burden of age-related disease in women.
Motivated our findings and the critical need to understand the determinants and drivers of sex differences in
major age-related disease outcomes, we propose to establish the Microvascular Aging and Eicosanoids
– Women’s Evaluation of Systemic aging Tenacity (MAE-WEST) (“You are never too old to become younger!”)
Specialized Center of Research Excellence (SCORE) on Sex Differences, in response to NIH RFA-OD-19-013.
Our goal is to form a robust and sustainable structure of academic activities centered on systematically
interrogating sex differences in the relationship among eicosanoids, microvascular dysfunction, and age-related
end-organ disease, with an initial focus on the microvascular aging effects on brain, heart, and kidney function.
This goal will be achieved by an outstanding collaborative team of clinician-scientists (with expertise in geriatrics,
cardiology, and nephrology), epidemiologists, basic and translational scientists, analytical chemists,
biostatisticians, and bioinformaticians. Leveraging our collective experience, resources, and infrastructure, we
will advance the scientific enterprise through 3 foundational projects aligned and complementary yet
independent. Project 3 will determine the causal role of sex-specific eicosanoids in receptor activation,
endothelial cell dysfunction and microvascular aging in experimental models and human endothelial
cells. This basic science project will establish a direct, causal role for sex-specific eicosanoids on endothelial
cell activation in vitro and microvascular dysfunction in experi...

## Key facts

- **NIH application ID:** 10696063
- **Project number:** 5U54AG065141-04
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** John YJ Shyy
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $576,738
- **Award type:** 5
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10696063

## Citation

> US National Institutes of Health, RePORTER application 10696063, MAE-WEST SCORE Project 3 Animal (5U54AG065141-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10696063. Licensed CC0.

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