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)

微血管老化和类二十烷酸 - 女性全身老化韧性评估 (MAE-WEST)（“你永远不会太老，变得更年轻！”）卓越研究专业中心 (SCORE)

• 批准号: 10450755
• 负责人: Cathleen Noel Bairey Merz
• 金额: $ 165.43万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10450755
• 关键词: Address; Advocacy; Age; Aging; Alzheimer' s disease related dementia; Awareness; Basic Science; Bioinformatics; Biological; Blood Vessels; Brain; Brain Diseases; Cardiology; Cardiovascular system; Cell physiology; Centers of Research Excellence; Chronic; Chronic Disease; Chronic Kidney Failure; Clinical Sciences; Communities; Data; Development; Disease; Disease Outcome; EFRAC; Education; Eicosanoids; Endothelial Cells; Enrollment; Epidemiologist; Evaluation; Exhibits; Experimental Models; FDA approved; Female; Foundations; Functional disorder; Funding; Geriatrics; Goals; Health; Heart; Heart Diseases; Heart failure; Human; In Vitro; Incidence; Individual; Inflammation; Inflammatory; Infrastructure; Kidney; Kidney Diseases; Leadership; Life Cycle Stages; Lipids; Longevity; Mass Spectrum Analysis; Measures; Mediating; Mediator of activation protein; Medical; Mentors; Mentorship; Microvascular Dysfunction; Molecular; Nature; Nephrology; Neurocognitive; Organ; Organ Model; Organism; Outcome; Pathway interactions; Pharmaceutical Preparations; Phenotype; Physiology; Plasma; Population Sciences; Positioning Attribute; Process; Receptor Activation; Renal function; Request for Applications; Research; Research Personnel; Research Project Grants; Resources; Role; Sampling; Scientific Advances and Accomplishments; Scientist; Secure; Sex Differences; Signal Transduction; Specialized Center; Structure; Syndrome; Therapeutic; Training; Variant; Whole Organism; Woman; Women' s Health; Work; age effect; age related; base; body system; burden of illness; career; clinical development; clinical phenotype; cohort; effective intervention; experience; forward genetics; frailty; functional decline; healthspan; heart function; improved; innovation; insight; male; men; microvascular aging; multidisciplinary; next generation; novel therapeutic intervention; operation; preservation; programs; prospective; receptor; response; science education; sex; sex disparity; sexual dimorphism; stressor; systemic inflammatory response; trait; translational scientist

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. !

项目摘要- MAE-WEST总体得分