BLR&D Research Career Scientist Award Application

BLR

• 批准号: 9764096
• 负责人: TONY WYSS-CORAY
• 金额: --
• 依托单位: VETERANS ADMIN PALO ALTO HEALTH CARE SYS
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9764096
• 关键词: Affect; Age; Aging; Alzheimer' s Disease; Award; Biology of Aging; Blood; Brain; Cells; Chemicals; Community Health; Dementia; Diet Modification; Disease; Environment; Exercise; Factor V; Funding Agency; Genetic study; Goals; Health Professional; Healthcare; Healthcare Systems; Human; Immune system; Impaired cognition; Incidence; Individual; Industry; Inflammation; Intervention; Killifishes; Label; Lead; Link; Longevity; Molecular; Mus; Muscle; Nerve Degeneration; Neurodegenerative Disorders; Organ; Organism; Parabiosis; Parkinson Disease; Patients; Phenotype; Physiological; Plasma; Prevalence; Process; Program Development; Proteins; Proteomics; Recombinant Inbred Strain; Research; Risk Factors; Rodent; Scientist; Stem cells; Testing; Time; Tissues; Veterans; Woman; age group; age related; aging brain; aging population; base; career; cell type; interest; men; microbiome; next generation sequencing; novel; programs; senescence; statistics; targeted treatment; therapeutic target; transcriptome

Currently, there are no treatments with significant disease modifying impact for major neurodegenerative diseases including Alzheimer’s disease and Parkinson’s disease. These diseases, even in their rare, autosomal dominant forms, are age-dependent, with age presenting the key risk factor for all sporadic forms of disease. Because the aging brain becomes increasingly vulnerable to neurodegeneration, slowing or reversing aspects of aging could therefore have a tremendous impact on the incidence and prevalence of these diseases. With a rapidly aging population, including aging Veterans pushing the boundaries of what our health care systems can absorb, there has been an unprecedented interest in aging and longevity from the public, funding agencies, and industry. Interestingly, studies of rodents and humans suggest that interventions targeted to individual organs or tissues, including muscle (e.g. through exercise), gut (e.g. through modifications of diet and the microbiome), and immune system (e.g. by reducing inflammation), can affect organismal aging. But how these organs may regulate aging processes is unknown. Dr. Wyss-Coray’s discoveries along with those of others indicate that the phenotypic age of individual organs is malleable and can be altered by exposing the organism to the systemic environment of an organism of a different age through heterochronic parabiosis or plasma transfer. Unexpectedly, Wyss-Coray recently found that heat-labile factors in blood plasma from young mice or young humans are sufficient to slow or reverse brain aging in mice. Conversely, factors in plasma from old mice or old humans can accelerate aspects of brain aging and cognitive impairment in mice. These surprising observations point in a new direction and prompted Dr. Wyss-Coray to study brain aging from a physiological, top-down perspective. Dr. Wyss-Coray is using chemical, bio-orthogonal manipulation of organisms, cutting edge proteomics, and next generation sequencing to answer how young blood revitalizes the old brain at the molecular level and to harness these processes towards reversing age-related changes and Alzheimer’s disease in the human brain. The goal of these studies is to develop new treatments for Veterans and patients with neurodegenerative diseases.

目前，没有对主要疾病的重大修改的治疗方法 神经退行性疾病，包括阿尔茨海默氏病和帕金森氏病。这些 疾病，即使以罕见的常染色体显性形式，随着年龄的 提出所有零星疾病的关键危险因素。因为衰老的大脑 变得越来越容易受到神经退行性的影响，放缓或逆转衰老的方面 因此，可能会对这些疾病的事件和患病率产生巨大影响。 人口迅速衰老，包括老化的退伍军人，朝着界限 我们的医疗保健系统可以吸收什么，对衰老有前所未有的兴趣 以及公众，资助机构和行业的寿命。有趣的是，对啮齿动物的研究 人类建议针对单个器官或组织的干预措施，包括肌肉 （例如，通过运动），肠道（例如，通过饮食和微生物组的修改）和免疫 系统（例如减少炎症）会影响有机老化。但是这些器官如何 调节老化过程是未知的。 Wyss-Coray博士的发现以及其他发现表明表型时代的发现 单个器官的可延展性，可以通过将生物暴露于系统性来改变 通过异核抛物线或等离子体的不同年龄的生物的环境 转移。出乎意料的是，Wyss-Coray最近发现血浆中血浆中的热量因子 年轻的小鼠或年轻人足以缓慢或反向小鼠的大脑衰老。反过来， 老鼠或老人血浆中的因素可以加速大脑衰老的各个方面 小鼠的认知障碍。这些令人惊讶的观察指向了一个新的方向， 促使Wyss-Coray博士从身体上自上而下的角度研究大脑衰老。博士 Wyss-Coray使用化学，生物正交操作，尖端 蛋白质组学和下一代测序，以回答年轻血液如何振兴旧 分子水平的大脑，并利用这些过程朝着与年龄相关的反向 人类大脑中的变化和阿尔茨海默氏病。这些研究的目的是发展 对退伍军人和神经退行性疾病患者的新治疗方法。