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分数项目1 在生活过程中，长期压力源导致多器官衰老和功能障碍，最终导致 临床疾病的发展。性仍然是对衰老的性质和节奏的关键决定者 长寿。在哺乳动物的物种中，更清楚的是，女性的年龄与 男性。随着人类年龄的增长，男女之间的生物衰老差异 变得更加明显，最终在女性占主导地位的许多重要病态 疾病状况，包括尤其是阿尔茨海默氏病和相关痴呆症（ADRD），心力衰竭 保留的射血分数（HFPEF），进行性慢性肾脏疾病（CKD）和全身脆弱。 女性占主导地位的机制尚不清楚，不是 用性激素或生存偏见的变化解释。我们的初步工作支持一个中心假设，即 炎症性类花生酸介质中的性二态性有助于微血管的性别差异 功能障碍，反过来，与年龄相关的多器官疾病的性别差异，包括ADRD，HFPEF和 CKD。阐明ADRD，HFPEF和CKD女性占主导地位的常见病理生理基础 是减少女性与年龄相关疾病过多的有效干预措施的关键。 激发了我们的发现以及了解性别差异的决定者和驱动力的批判性需求 与年龄相关的主要疾病结局，我们建议建立微血管衰老和类花生素 - 妇女对系统性老化的耐性评估（Mae-West）（“您永远不会太老，无法年轻！”） 针对NIH RFA-OD-19-013的专业研究中心卓越研究中心（得分）。 我们的目标是形成以系统为中心的学术活动的强大而可持续的结构 询问类花生酸，微血管功能障碍和与年龄有关的性别差异 最初的器官疾病，最初侧重于微血管衰老对大脑，心脏和肾功能的影响。 这个目标将由临床科学家的杰出合作团队实现（具有老年医学专业知识， 心脏病学和肾脏病），流行病学家，基础和翻译科学家，分析化学家， 生物统计学家和生物信息学家。利用我们的集体经验，资源和基础设施，我们 将通过3个结盟和补充的基础项目推进科学企业 独立的。项目1将确定类花生酸与微血管的性别特异性关系 社区中主要的最终器官疾病结局的功能障碍和事件。这个人口 科学项目将检查数百种循环类花生酸的纵向变化：（i）离散 微血管功能的度量； （ii）多系统（神经认知，心血管，肾脏）的轨迹 以及全球功能下降； （iii）跨越明显的管道疾病（ADRD，HFPEF，CKD）的事件 在两个独立的社区人群中，老年男性和男性患者。