MAE-WEST SCORE Leadership Administrative Core

MAE-WEST SCORE 领导力行政核心

基本信息

批准号：
10198756
负责人：
Cathleen Noel Bairey Merz
金额：
$ 23.07万
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/10198756
关键词：
Address Administrative Coordination Advisory Committees Advocate Age Aging Alzheimer&apos s disease related dementia Annual Reports Area Basic Science Bioinformatics Biological Biological Aging Biostatistics Core Blood Vessels Brain Budgets Cardiology Centers of Research Excellence Chronic Chronic Kidney Failure Chronology Clinical Research Clinical Sciences Collaborations Communication Communities Data Set Databases Disease Disease Outcome EFRAC Educational Curriculum Educational workshop Eicosanoids Elderly Ensure Epidemiologist Evaluation Failure Feedback Female Financial Support Foundations Functional disorder Funding Generations Geriatrics Goals Gonadal Steroid Hormones Grant Heart failure Human Inflammation Inflammatory Infrastructure Institution Interdisciplinary Study Investigation Lead Leadership Letters Life Cycle Stages Longevity Mediator of activation protein Mentors Microvascular Dysfunction Mission Monitor Morbidity - disease rate Nature Nephrology Organ Participant Pilot Projects Population Sciences Preparation Productivity Progress Reports Public Health Publications Renal function Reporting Request for Applications Research Research Personnel Research Project Grants Resource Allocation Resource Sharing Resources Scientific Advances and Accomplishments Scientist Seeds Services Sex Differences Specialized Center Structure Training Training Activity Translating Translations Variant Woman Women&apos s Health Work age effect age related base career career development clinical development data dissemination data sharing effective intervention experience frailty heart function improved inter-institutional male meetings men microvascular aging next generation operation organizational structure preservation programs public repository response scientific organization sex sexual dimorphism stressor translational scientist

项目摘要

Project Abstract – MAE-WEST SCORE LAC 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. To realize the full potential of this ambitious scientific and educational agenda, we have established a Leadership Administrative Core, for overseeing operations, fiduciary responsibility, and enabling efficiency. In establishing the MAE-WEST SCORE, we will extend from existing collaborations and formalize an organization of scientific and mentoring leadership that is intended to prioritize inter-institutional as well as inter-disciplinary integration of all activities, including routine sharing of research findings across the major areas of population, clinical, and basic science.

项目摘要 - Mae-West分数LAC 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。为了实现这一雄心勃勃的科学和教育议程的全部潜力，我们已经建立了领导行政核心，用于监督运营，信托责任和提高效率。在建立MAE-West分数，我们将从现有的合作中扩展并正式化组织旨在优先考虑机构间和跨学科的科学和心理领导所有活动的整合，包括在主要人口主要领域的研究结果的常规共享，临床和基础科学。