MAE-WEST SCORE Career Enhance Core

MAE-WEST SCORE 职业提升核心

基本信息

批准号：
10450757
负责人：
Cathleen Noel Bairey Merz
金额：
$ 14.25万
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/10450757
关键词：
Address Advocate Age Aging Alzheimer&apos s disease related dementia Analytical Chemistry Area Basic Science Bioinformatics Biological Biological Aging Biometry Blood Vessels Brain California Cardiology Centers of Research Excellence Chemistry Chronic Chronic Disease Chronic Kidney Failure Chronology Clinical Clinical Research Clinical Trials Collaborations Communities Data Analytics Dementia Development Disease Disease Outcome EFRAC Education Eicosanoids Elderly Environment Epidemiologist Epidemiology Evaluation Faculty Failure Female Foundations Functional disorder Funding Geriatrics Gerontology Goals Gonadal Steroid Hormones Grant Heart Heart failure Human Inflammation Inflammatory Infrastructure Lead Life Cycle Stages Longevity Measurement Mediator of activation protein Medical Medical center Mentors Methodology Microvascular Dysfunction Mission Molecular Profiling Morbidity - disease rate Nature Nephrology Neurology Ophthalmology Organ Physiology Pilot Projects Productivity Public Health Renal function Request for Applications Research Research Activity Research Methodology Research Personnel Research Training Resources Scientific Advances and Accomplishments Scientist Seeds Sex Differences Specialized Center Structure Techniques Testing Training Training Activity Translating Translational Research Translations United States National Institutes of Health Universities Variant Woman Women&apos s Health Work age effect age related career career development clinical development effective intervention experience frailty hands on research health difference heart function implementation intervention improved infrastructure development innovation interdisciplinary approach men microvascular aging multidisciplinary neurocognitive test next generation population health preservation programs response sex sex disparity sexual dimorphism stressor translational scientist

项目摘要

Project Abstract – MAE-WEST SCORE CEC 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. 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. To promote and enhance the development of the next generation of early career investigators who are committed to studying sex differences in biomedicine, our MAE-WEST SCORE program will provide a robust, multi-disciplinary Career Enhancement Core. Methodological expertise areas include: epidemiology, clinical trials, basic science, analytical chemistry, biostatistics and bioinformatics, neurocognitive testing, integrated physiology, and global functional assessments. Content and clinical areas of expertise that will maximize the potential for translation of research findings to practice include: geriatrics and gerontology, neurology and neuro- ophthalmology, cardiology, nephrology, and women’s health.

项目摘要 – MAE-WEST SCORE CEC 在生命过程中，慢性压力源会导致多器官衰老和功能障碍，并最终导致性别仍然是衰老的性质和速度的关键决定因素。随着人类实际年龄的增长，女性和男性之间的生物衰老存在差异。变得更加明显，最终导致许多重要病态的女性占主导地位疾病状况，特别是阿尔茨海默氏病和相关痴呆症 (ADRD)、心力衰竭射血分数保留（HFpEF）、进行性慢性肾病（CKD）以及全身虚弱。这些主要疾病的女性占主导地位的机制仍然未知，也不明确我们的初步工作支持一个中心假设：炎症类二十烷酸介质的性别二态性导致微血管的性别差异功能障碍，进而导致与年龄相关的多器官疾病的性别差异，包括 ADRD、HFpEF 和阐明 ADRD、HFpEF 和 CKD 女性占主导地位的共同病理生理学基础是采取有效干预措施减少妇女因年龄相关疾病而过度负担的关键。激发了我们的发现以及了解性别差异的决定因素和驱动因素的迫切需要主要的年龄相关疾病结果，我们建议建立微血管衰老和类二十烷酸 – 女性系统衰老韧性评估（MAE-WEST）（“你永远不会太老，不会变得更年轻！”）性别差异专业卓越研究中心 (SCORE)，响应 NIH RFA-OD-19-013。我们的目标是形成一个稳健且可持续的学术活动结构，以系统地为中心探讨类二十烷酸、微血管功能障碍和年龄相关性之间关系的性别差异终末器官疾病，最初关注微血管老化对大脑、心脏和肾脏功能的影响。这一目标将由杰出的临床医生科学家合作团队（具有老年病学、心脏病学和肾病学）、流行病学家、基础和转化科学家、分析化学家、我们利用生物统计学家和生物信息学家的集体经验、资源和基础设施。将通过 3 个相互协调且互补的基础项目推进科学事业促进和加强下一代早期职业调查员的发展。致力于研究生物医学中的性别差异，我们的 MAE-WEST SCORE 计划将提供强大的、多学科职业提升核心方法论专业领域包括：流行病学、临床。试验、基础科学、分析化学、生物统计学和生物信息学、神经认知测试、综合生理学、整体功能评估的内容和临床领域的专业知识，将最大限度地发挥作用。将研究成果转化为实践的潜力包括：老年病学和老年学、神经病学和神经病学眼科、心脏病学、肾病学和妇女健康。