MAE-WEST SCORE Research Support Core - Bioinformatics Core

MAE-WEST SCORE 研究支持核心 - 生物信息学核心

• 批准号: 10450758
• 负责人: Susan Cheng
• 金额: $ 13.48万
• 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/10450758
• 关键词: Age; Aging; Alzheimer' s disease related dementia; Animals; Bioinformatics; Biological Aging; Biological Markers; Biometry; Biostatistical Methods; Blood Vessels; Brain; Cardiology; Cell membrane; Cells; Centers of Research Excellence; Chronic; Chronic Kidney Failure; Chronology; Clinical; Complex; Consult; Data; Data Analyses; Data Scientist; Data Sources; Disease; Disease Outcome; EFRAC; Eicosanoids; Elderly; Endothelial Cells; Ensure; Epidemiologist; Evaluation; Failure; Female; Foundations; Functional disorder; Funding; Generations; Genomics; Geriatrics; Goals; Gonadal Steroid Hormones; Grant; Heart failure; Human; Inflammation; Inflammatory; Infrastructure; Knowledge; Leadership; Life Cycle Stages; Lipids; Longevity; Mass Spectrum Analysis; Mediating; Mediator of activation protein; Methodology; Methods; Microvascular Dysfunction; Morbidity - disease rate; Nature; Nephrology; Organ; Organization and Administration; Outcome; Pilot Projects; Plasma; Proteomics; Public Health; Quality Control; Renal function; Request for Applications; Research Methodology; Research Personnel; Research Support; Resource Sharing; Resources; Science; Scientific Advances and Accomplishments; Scientist; Services; Sex Differences; Specialized Center; Standardization; Statistical Data Interpretation; Statistical Methods; Stress; Structure; Techniques; Time; Training; Variant; Woman; Work; age effect; age related; career; clinical development; data management; effective intervention; epigenomics; experience; frailty; heart function; high dimensionality; high throughput analysis; improved; male; meetings; men; metabolomics; microvascular aging; preservation; programs; prospective; response; sex; sexual dimorphism; small molecule; stressor; tool; trait; transcriptomics; translational potential; translational scientist

Project Abstract – MAE-WEST SCORE Biostatistics and Bioinformatics Core 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. We will establish a dedicated Resource Support Core – a Biostatistical and Bioinformatics Core (BBC) that will be intentionally created as standalone organization within the larger MAE-WEST SCORE. This organizational feature will not only maximize resource sharing across the project aims but will also ensure the ability to separately and independently augment the methodological training of early career investigators and, importantly, timely provision of in-kind services for trainee pilot projects. The dedicated effort of the BBC will allow efficient generation of preliminary data for acquiring additional and ancillary grant funding for both early career and core activities.

项目摘要 – MAE-WEST SCORE 生物统计学和生物信息学核心 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 临床疾病的发展。性别仍然是衰老性质和速度的关键决定因素，并最终 长寿。在哺乳动物物种中，更明显的是，雌性的年龄与雄性不同。 男性。随着人类实际年龄的增长，女性和男性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，也不清楚 可以用性激素的变化或生存偏差来解释。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 慢性肾病。阐明 ADRD、HFpEF 和 CKD 女性占多数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、 生物统计学家和生物信息学家。凭借我们的集体经验、资源和基础设施，我们 将通过 3 个相互协调且互补的基础项目推进科学事业 独立的。我们将建立专门的资源支持核心——生物统计和生物信息学核心 (BBC) 将在更大的 MAE-WEST SCORE 中有意创建为独立组织。这 组织特征不仅可以最大限度地实现项目目标的资源共享，而且还可以确保 能够单独和独立地增强早期职业调查人员的方法培训，并且， 重要的是，及时为实习生试点项目提供实物服务。 BBC 的不懈努力将 允许有效生成初步数据，以获取早期的额外和辅助赠款资金 职业和核心活动。