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分数CEC 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。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庄严性评估（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。促进和增强下一代职业调查人员的发展致力于研究生物医学的性别差异，我们的MAE-West分数计划将提供强大的，多学科职业增强核心。方法论专业知识领域包括：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，综合生理学和全球功能评估。内容和专业知识的临床领域将最大化进行研究结果翻译的潜力包括：老年医学和老年学，神经病学和神经学眼科，心脏病学，肾脏病和妇女健康。