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MAE-WEST SCORE Project 2 Clinical

MAE-WEST SCORE 项目 2 临床

基本信息

批准号：
10198761
负责人：
Cathleen Noel Bairey Merz
金额：
$ 73.29万
依托单位：
CEDARS-SINAI MEDICAL CENTER
依托单位国家：
美国
项目类别：
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/10198761
关键词：
Address Age Aging Alzheimer&apos s disease related dementia Angiotensin Receptor Angiotensin-Converting Enzyme Inhibitors Anti-Inflammatory Agents Biological Aging Biology Blood Vessels Brain Cardiac Cardiology Cell physiology Centers of Research Excellence Chronic Chronic Kidney Failure Chronology Clinical Clinical Sciences Clinical Trials Cognitive Coronary Data Development Diagnostic tests Disease Disease Outcome Disease Progression EFRAC Eicosanoids Elderly Endothelial Cells Endothelium Enrollment Epidemiologist Evaluation FDA approved Failure Female Foundations Functional disorder Funding Geriatrics Goals Gonadal Steroid Hormones Heart Heart failure Human Impairment Individual Inflammation Inflammatory Inflammatory Response Infrastructure Intervention Trial Investigation Ischemia Kidney Lead Life Cycle Stages Longevity Magnetic Resonance Imaging Measures Mediator of activation protein Medical Men&apos s Role Microvascular Dysfunction Molecular Morbidity - disease rate National Institute on Aging Nature Nephrology Organ Peripheral Phenotype Physiological Physiology Plasma Play Population Analysis Process Prospective Studies Public Health Randomized Renal function Request for Applications Research Resources Role Sampling Scientific Advances and Accomplishments Scientist Severities Sex Differences Specialized Center Stress Structure Testing Urine Variant Woman Women&apos s Role Work age effect age related base body system burden of illness clinical development clinical phenotype effective intervention endothelial dysfunction experience frailty functional status heart function improved intervention effect kidney dysfunction male men microvascular aging population based preservation prevent prospective response retinal imaging sex sexual dimorphism stressor systemic inflammatory response targeted treatment tonometry trait translational scientist treatment as usual treatment strategy

项目摘要

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 microvascular aging traits across major organ systems (brain, heart, kidney, systemic frailty) and evaluate the effects of intensive medical treatment with high-intensity statin plus ACEi or ARB therapy on both eicosanoid profiles and total microvascular disease burden.

项目摘要- MAE-WEST SCORE项目2