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（由申请人提供）：许多学术团体和生命科学的研究方法是延迟的测试方法 - 对绝大多数严重的人类疾病的重要风险是对敌对的至关重要的。 ，基于器官增强的microRNA（miRNA）Lasma的分析，我们在此SBIR I期中对不同器官的衰老生物标志物进行了较早的检测。脑老化的特征是神经突和突触损失和神经元死亡（海马，中脑，小脑，皮层，垂体）并存在于神经突和突触中，并将与炎症相关的miRNA测试，将被视为在脑含有脑含量的Mirna Pairs rker Mirna Pairs cognment（Plassma）中（发现了脑含量）。 MCI）ACY，从年龄匹配的对照中，从正常认知到MCI的进展，在衰老的严重大脑 - 富含大脑的预先研究中，彼此之间的疾病彼此之间的疾病相同。 P <0.001的年龄段。 1在II阶段的某些ES中，与年龄相关的动力学依赖性差异将通过与1,000多名血浆样品进行研究，从而汇集了20至90岁的受试者在其他测试中，将击败衰老器官的生物标志物，以确定依赖年龄的miRNA生物标志物浓度范围，定义正常老化的长期目标。并用于监测衰老，用于评估治疗剂和生活方式的变化，这些变化延迟了相关疾病的衰老。