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MAE-WEST RSC - Eicosanoids Profiling Core

MAE-WEST RSC - 类二十烷酸分析核心

基本信息

批准号：
10450759
负责人：
Mohit Jain
金额：
$ 24.88万
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/10450759
关键词：
Acids Age Aging Alzheimer&apos s disease related dementia Animal Model Animals Anti-Inflammatory Agents Arachidonic Acids Basic Science Bioinformatics Biological Biological Aging Biological Assay Biological Process Biometry Blood Circulation Blood Vessels Brain Cardiology Centers of Research Excellence Chronic Chronic Kidney Failure Chronology Clinical Research Complex Core Facility Data Development Disease EFRAC Eicosanoids Eicosapentaenoic Acid Elderly Endothelial Cells Endothelium Ensure Epidemiologist Equilibrium Evaluation Exhibits Failure Family Female Foundations Functional disorder Funding Generations Geriatrics Goals Gonadal Steroid Hormones Grant Heart failure Human Individual Inflammation Inflammatory Inflammatory Response Infrastructure Life Cycle Stages Lipids Longevity Mass Spectrum Analysis Measures Mediator of activation protein Metabolic syndrome Methodology Methods Microvascular Dysfunction Molecular Morbidity - disease rate Nature Nephrology Obesity Organ Organization and Administration Physiological Pilot Projects Plasma Play Polyunsaturated Fatty Acids Population Study Public Health Renal function Reproducibility Request for Applications Research Methodology Research Personnel Resolution Resource Sharing Resources Risk Role Sampling Scientific Advances and Accomplishments Scientist Services Sex Differences Specialized Center Standardization Stress Structure System TNF gene Time Training Variant Woman Work advanced analytics age effect age related antagonist burden of illness career clinical development cohort computational chemistry cytokine data handling data standards effective intervention experience frailty gamma-Linolenic Acid heart function high dimensionality improved in vivo indexing inflammatory marker insight liquid chromatography mass spectrometry male men microvascular aging novel preservation prospective response sex sex disparity sexual dimorphism stressor systemic inflammatory response tool translational scientist

项目摘要

Project Abstract – MAE-WEST SCORE Eicosanoids Profiling Core 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. 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. We will establish a dedicated Resource Support Core - an Eicosanoids Profiling Core (EPC) that will be intentionally created as standalone organization within the larger MAE-WEST SCORE. This organizational feature will not only maximize resource sharing across the project aims but also ensure the ability to separately and independently augment the methodological training of early career investigators and, importantly, timely provision of in-kind services for trainee pilot projects. The dedicated effort of the EPC will allow efficient generation of preliminary data for acquiring additional and ancillary grant funding for both early career and core activities, which will additionally contribute to the long-term sustainability of the MAE-WEST SCORE as a whole.

项目摘要- MAE-WEST SCORE二十烷类分析核心