Circulating organ-enriched microRNAs as biomarkers of aging

富含循环器官的 microRNA 作为衰老生物标志物

• 批准号: 9139280
• 负责人: SAMUIL R UMANSKY
• 金额: $ 22.46万
• 依托单位: DIAMIR, LLC
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-01 至 2016-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9139280
• 关键词: Age; Aged, 80 and over; Aging; Alzheimer' s Disease; Anus; Area; Behavior Therapy; Biological Assay; Biological Markers; Biological Sciences; Blood; Brain; Brain region; Cells; Centenarian; Cerebellum; Characteristics; Cognition; Cognitive; Data; Data Analyses; Detection; Development; Diagnostic; Diet; Disease; Early Diagnosis; Ethnic Origin; Evaluation; FRAP1 gene; Food Supplements; Functional disorder; Gender; Goals; Hippocampus (Brain); In Vitro; Inflammation; Inflammatory; Life; Life Style; Longevity; Lung; Malignant Neoplasms; Marketing; MicroRNAs; Midbrain structure; Molecular; Monitor; Natural Products; Neurites; Neurodegenerative Disorders; New York; Organ; Parabiosis; Parkinson Disease; Pathway interactions; Phase; Pituitary Gland; Plasma; Process; Race; Regimen; Risk Factors; Sampling; Sensitivity and Specificity; Small Business Innovation Research Grant; Smoking; Synapses; Technology; Testing; Therapeutic; Therapeutic Intervention; Validation; Women' s Group; Work; age difference; age group; age related; aging brain; anti aging; base; body system; brain health; candidate marker; circulating microRNA; clinical Diagnosis; commercial application; cost effective; gastrointestinal system; human disease; human old age (65+); innovation; knowledge base; men' s group; microRNA biomarkers; mild cognitive impairment; minimally invasive; molecular diagnostics; nervous system disorder; neuron loss; normal aging; phase 1 study; public health relevance; residence; software development; success

 DESCRIPTION (provided by applicant): A number of academic groups and life sciences companies are developing and testing approaches to delay aging -- the most significant risk factor for the vast majority of serious human diseases. Critical for these efforts is the development and validation of minimally invasive, cost-effective biomarkers of aging. DiamiR, a molecular diagnostics company, has developed proprietary platform technology for early detection and moni- toring of pathophysiological processes in different organs based on analysis of organ-enriched microRNA (miRNA) pairs in plasma. In this SBIR Phase I we propose to use the technology to select effective biomarkers of brain aging. Brain aging is characterized by neurite and synapse dysfunction and loss and neuronal death. A hypothesis being tested in the current proposal is that these processes can be detected in vitro by quantitative (RT-qPCR) analysis of brain-enriched and inflammation-associated miRNAs circulating in the blood. miRNAs enriched in different brain regions (hippocampus, midbrain, cerebellum, cortex, pituitary gland) and present in neurites and synapses, and several inflammation-associated miRNAs will be tested as biomarker candidates. Our previous studies on brain health produced highly promising results: biomarker miRNA pairs selected among brain-enriched miRNAs circulating in plasma were found to detect Mild Cognitive Impairment (MCI) with up to 96% accuracy, predict progression from normal cognition to MCI with 84% accuracy 1-5 years prior to clinical diagnosis, and differentiate Alzheimer's and Parkinson's diseases from age-matched control and from each other with accuracy >85%. In the preliminary study on aging several brain-enriched miRNAs were found to differentiate cognitively normal subjects of two age groups with p < 0.05 to p < 0.001. The current study will be performed using plasma samples prospectively collected at the New York Blood Center. Specific aims include (1) assessing feasibility of the approach and selecting miRNA biomarker pairs effectively differentiating younger (26-35 year-old) from older (56-65 year-old) healthy subjects (20 samples per group); and (2) using sets of miRNA biomarker pairs selected in Aim 1 to evaluate age-related dynamics and gender-dependent differences in plasma samples collected from 26 to 75 year-old healthy subjects (100 samples in total). In Phase II, DiamiR will assemble a knowledgebase by conducting studies with 1,000+ plasma samples collected from 20 to 90 year-old subjects. Further, miRNAs enriched in other than brain organs will be tested as biomarkers of aging of these organs. The generated data will be used to determine age-dependent ranges of concentrations of miRNA biomarker pairs defining normal aging. The long-term goal of the project is to develop sensitive, minimally invasive molecular assays for evaluation and monitoring of aging in the brain and other organs. The assays will be developed as in vitro diagnostics (IVD) and used for monitoring of aging, for assessment of therapeutic regimens and life style changes aimed at delaying (or reversing) normal aging, and for early detection of anomalies characteristic of aging associated diseases.

 描述（由应用程序提供）：许多学术团体和生命科学公司正在开发和测试延迟衰老的方法 - 绝大多数严重人类疾病的最重要危险因素。这些努力至关重要的是衰老的最低侵入性，具有成本效益的生物标志物的发展和验证。 Diamir是一家分子诊断公司Diamir，基于对等离子体中器官增强的microRNA（miRNA）对的分析，开发了用于早期检测和游览不同器官病理生理过程的专有平台技术。在此SBIR阶段，我们建议使用该技术选择大脑衰老的有效生物标志物。脑衰老的特征是神经和突触功能障碍以及丧失和神经元死亡。在当前建议中检验的一个假设是，可以通过定量（RT-QPCR）分析脑增强和炎症相关的miRNA，在体外检测到这些过程。富含大脑区域的miRNA（海马，中脑，小脑，皮层，垂体腺体）并存在于神经运动和突触中，几种与炎症相关的miRNA将被视为生物标志物候选者。我们先前关于大脑健康的研究产生了很高的希望结果：在血浆中循环的脑增强的miRNA中选择的生物标志物miRNA对可检测到轻度认知障碍（MCI），准确性高达96％，可预测从正常认知到MCI的进展，并从临床诊断和临床诊断前的临床诊断和施加量从正常认知到MCI，并通过84％的准确性，并从临床诊断中进行了分化。彼此的精度> 85％。在衰老的初步研究中，发现几种富含脑部的miRNA可以区分两个年龄组的认知正常受试者，p <0.05至p <0.001。当前的研究将使用在纽约血液中心前瞻性收集的血浆样品进行。具体目的包括（1）评估该方法的可行性并选择miRNA生物标志物对有效地区分了年龄较小（26-35岁）与老年人（56-65岁）健康受试者（每组20个样本）； （2）使用在AIM 1中选择的miRNA生物标志物对来评估与年龄相关的动力学和性别依赖性差异，这些血浆样本从26至75岁的健康受试者（总共100个样本）收集的血浆样本中。在第二阶段，Diamir将通过对20至90岁受试者收集的1,000多个血浆样本进行研究来组装知识库。此外，富含大脑器官以外的miRNA将被测试为这些器官衰老的生物标志物。生成的数据将用于确定MiRNA生物标志物浓度的年龄依赖性范围定义正常衰老。该项目的长期目标是开发敏感的，微创的分子测定法，以评估和监测大脑和其他器官的衰老。该测定法将作为体外诊断（IVD）开发，用于监测衰老，评估旨在延迟（或逆转）正常衰老的治疗方案和生活方式变化，以及早期发现相关疾病的异常特征。