BLR&D Research Career Scientist Award Application

BLR

• 批准号: 9911974
• 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 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9911974
• 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; 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; stem cells; 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，没有治疗方法对主要疾病具有显著的疾病改善作用。 神经退行性疾病，包括阿尔茨海默病和帕金森病。这些 疾病，即使是罕见的常染色体显性形式，也是年龄依赖性的，随着年龄的增长， 这是所有散发性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化的影响，减缓或逆转衰老的各个方面。 因此可能对这些疾病的发病率和流行率产生巨大影响。 随着人口的迅速老龄化，包括老年退伍军人， 我们的医疗系统所能吸收的，人们对老龄化的兴趣前所未有 和长寿的问题。有趣的是， 而人类则认为，针对单个器官或组织（包括肌肉）的干预措施， (e.g.通过运动），肠道（例如通过饮食和微生物组的改变），和免疫 系统（例如通过减少炎症），可以影响生物体衰老。但这些器官如何 调节衰老过程是未知的。 Wyss-Coray博士与其他人的发现沿着表明， 个体器官的可塑性，可以通过将生物体暴露于系统性环境中而改变。 通过异时共生或血浆， 转移令人意想不到的是，Wyss-Coray最近发现， 年轻的小鼠或年轻的人类足以减缓或逆转小鼠的脑老化。相反地， 来自老年小鼠或老年人的血浆中的因子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结果指出了一个新的方向， 这促使Wyss-Coray博士从生理学的自上而下的角度研究大脑衰老。博士 Wyss-Coray是使用化学，生物正交操纵生物，尖端 蛋白质组学和下一代测序，以回答年轻血液如何振兴老年人 在分子水平上改变大脑，并利用这些过程来逆转与年龄相关的 变化和阿尔茨海默病的关系。这些研究的目的是发展 为退伍军人和神经退行性疾病患者提供新的治疗方法。