# MAE-WEST SCORE Project 2 Clinical

> **NIH NIH U54** · CEDARS-SINAI MEDICAL CENTER · 2023 · $584,247

## Abstract

Project Abstract – MAE-WEST SCORE Project 2
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 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 2 will determine the sex-
specific association of eicosanoids with microvascular physiology in women and men and the role of
FDA approved agents in modulation of total microvascular disease burden. In a sample of women and
men with deep clinical phenotyping, this clinical science project will examine sex differences in the relations of
eicosanoids with the co-occurrence of microva...

## Key facts

- **NIH application ID:** 10696054
- **Project number:** 5U54AG065141-04
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** Cathleen Noel Bairey Merz
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $584,247
- **Award type:** 5
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10696054

## Citation

> US National Institutes of Health, RePORTER application 10696054, MAE-WEST SCORE Project 2 Clinical (5U54AG065141-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10696054. Licensed CC0.

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