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The Microvascular Aging and Eicosanoids - Women's Evaluation of Systemic Aging Tenacity (MAE-WEST) ("You are never too old to become younger!") Specialized Center for Research Excellence (SCORE)

Award Number: U54AG065141
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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The Microvascular Aging and Eicosanoids - Women's Evaluation of Systemic Aging Tenacity (MAE-WEST) ("You are never too old to become younger!") Specialized Center for Research Excellence (SCORE) - Project Abstract – MAE-WEST SCORE Overall Women age differently than men across the lifespan, culminating in a female predominance in morbid chronic diseases such as heart failure with preserved ejection fraction, Alzheimer’s disease and related dementias, and chronic kidney disease. Women also tend to develop multi-organ syndromes (heart-brain, heart-kidney) more frequently than men. The mechanisms underlying sex-specific differences in multi-organ dysfunction remain poorly understood. Prior work indicates that women exhibit accelerated microvascular aging, a process implicated in disorders of the heart, brain, and kidney. In this context, systemic inflammation has emerged as a primary driver of both microvascular dysfunction and the development of these chronic disease states. Preliminary data from our group indicates that eicosanoids, a diverse group of bioactive lipids that serve as the upstream mediators of systemic inflammation, can influence endothelial cell function, exhibit sexual dimorphism in circulating plasma, and are related to certain vascular phenotypes. Given these findings, we hypothesize that sexual dimorphism in both local and systemic eicosanoid variation contributes to sex differences in microvascular dysfunction and, in turn, to sex differences in age-related multi-organ disease. Motivated by our early findings and the critical need to understand the determinants and drivers of sex differences in age-related disease outcomes, we propose to create the Microvascular Aging and Eicosanoids –Women’s Evaluation of Systemic aging Tenacity (MAE-WEST) Specialized Center of Research Excellence (SCORE) on Sex Differences. Leveraging our collective expertise, we plan to advance the understanding of sex-specific molecular drivers of chronic microvascular and end-organ disease through 3 foundational projects. In Project 1, we will examine longitudinal variation in circulating eicosanoid levels in relation to age-related alterations in microvascular function in end-organ (cardiovascular, neurocognitive, renal) disease traits in 2 large community cohorts. In Project 2, we will prospectively enroll and deeply phenotype a cohort of women and men to assess the relation of eicosanoids with organ-specific as well as global burden of microvascular disease, as well as their response to a trial of intensive medical therapy with FDA-approved agents (statins and ACEi/ARB). Finally, in Project 3, we will study the mechanistic role of sex-specific eicosanoid signaling on human endothelial cell function and on microvascular function in experimental models of organ-specific disease as well as whole organism aging. As an integral part of this SCORE, we will establish a Career Enhancement Center that will provide robust training and mentorship for trainees and junior investigators. Collectively, this highly collaborative and innovative SCORE aims to transform our understanding of sex differences in microvascular and chronic multi-organ diseases and, in turn, enable effective interventions through inter-disciplinary science, education, and advocacy. !


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2024	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Aging Research	000	5	3/26/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $1,828,533 )
2024	2024	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Aging Research	001	5	8/9/2024	NON-COMPETING CONTINUATION	$1,663,829
2024	2024	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Aging Research	002	5	8/22/2024	SUPPLEMENT FOR EXPANSION	$164,704
2024	2023	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Aging Research	000	4	11/17/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,828,533

Issue Date FY: 2023 ( Subtotal = $1,823,067 )
2023	2023	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Aging Research	001	4	8/9/2023	NON-COMPETING CONTINUATION	$1,658,363
2023	2023	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Aging Research	002	4	8/11/2023	SUPPLEMENT FOR EXPANSION	$164,704
2023	2022	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Aging Research	000	3	1/27/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,823,067

Issue Date FY: 2022 ( Subtotal = $1,654,296 )
2022	2022	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Aging Research	002	3	9/5/2022	NON-COMPETING CONTINUATION	$0
2022	2022	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Aging Research	001	3	9/2/2022	NON-COMPETING CONTINUATION	$1,654,296
2022	2021	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Aging Research	000	2	8/30/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,654,296

Issue Date FY: 2021 ( Subtotal = $1,670,170 )
2021	2021	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Aging Research	000	2	7/14/2021	NON-COMPETING CONTINUATION	$1,670,170
2021	2021	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Aging Research	001	2	7/22/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,670,170

Issue Date FY: 2020 ( Subtotal = $1,767,973 )
2020	2020	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Aging Research	000	1	6/19/2020	NEW	$1,767,973
														Subtotal = $1,767,973

Grand Total All Awards = $8,744,039

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The Microvascular Aging and Eicosanoids - Women's Evaluation of Systemic Aging Tenacity (MAE-WEST) ("You are never too old to become younger!") Specialized Center for Research Excellence (SCORE)

Award Number: U54AG065141

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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