MAE-WEST SCORE Project 1 Population

MAE-WEST SCORE 项目 1 人口

• 批准号: 10198760
• 负责人: Susan Cheng
• 金额: $ 19.45万
• 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/10198760
• 关键词: Acute; Age; Aging; Alzheimer' s disease related dementia; Anti-Inflammatory Agents; Atherosclerosis Risk in Communities; Biological; Biological Aging; Blood Vessels; Brain; Cardiology; Cardiovascular system; Centers of Research Excellence; Chronic; Chronic Disease; Chronic Kidney Failure; Chronology; Clinical; Communities; Data; Development; Disease; Disease Outcome; EFRAC; Eicosanoids; Elderly; Endothelium; Epidemiologist; Etiology; Evaluation; Exhibits; Exposure to; Failure; Female; Foundations; Framingham Heart Study; Functional disorder; Geriatrics; Goals; Gonadal Steroid Hormones; Heart; Heart failure; Hormonal; Human; Impaired cognition; Incidence; Individual; Inflammation; Inflammatory; Inflammatory Response; Infrastructure; Investigation; Kidney; Life Cycle Stages; Lipids; Longevity; Mass Spectrum Analysis; Measures; Mediating; Mediation; Mediator of activation protein; Methods; Microvascular Dysfunction; Morbidity - disease rate; Nature; Nephrology; Neurocognitive; Organ; Outcome; Participant; Patients; Pattern; Persons; Physical Function; Physical activity; Plasma; Population; Population Sciences; Predisposition; Process; Prognosis; Public Health; Renal function; Reporting; Request for Applications; Resources; Risk; Risk Factors; Role; Sampling; Sampling Studies; Scientific Advances and Accomplishments; Scientist; Sex Differences; Specialized Center; Stress; Structure; System; Techniques; Thromboplastin; Time; Variant; Vascular Diseases; Woman; Work; age effect; age related; base; clinical development; cohort; effective intervention; experience; follow-up; frailty; functional decline; healthy aging; heart function; improved; indexing; male; men; microvascular aging; mortality; offspring; older men; older women; population based; preservation; response; sex; sexual dimorphism; small molecule; stressor; trait; translational scientist; vascular risk factor

Project Abstract – MAE-WEST SCORE Project 1 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. 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 1 will determine the sex-specific relations of eicosanoids with microvascular dysfunction and incidence of major end-organ disease outcomes in the community. This population science project will examine longitudinal variation in hundreds of circulating eicosanoids in relation to: (i) discrete measures of microvascular function; (ii) trajectories of multi-system (neurocognitive, cardiovascular, renal) as well as global functional decline; and, (iii) incidence of overt end-organ disease (ADRD, HFpEF, CKD) across aging women and men patient, in two independent community-based cohorts.

项目摘要- MAE-WEST SCORE项目