BLR&D Research Career Scientist Award Application

目前，还没有对重大疾病有显著改善作用的治疗方法。 神经退行性疾病，包括阿尔茨海默病和帕金森氏病。这些 疾病，即使是罕见的常染色体显性疾病，也是与年龄相关的。 是所有散发性疾病的关键风险因素。因为老化的大脑 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，包括老龄化的退伍军人正在突破 我们的医疗保健系统能够吸收的东西，人们对老龄化产生了前所未有的兴趣 以及来自公众、资助机构和行业的长寿。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进行干预，包括肌肉 (例如通过锻炼)、肠道(例如通过改变饮食和微生物群)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 对衰老过程的调控尚不清楚。 Wyss-Coray博士的发现以及其他人的发现表明，表型年龄 是可塑性的，并且可以通过将有机体暴露在系统中而改变 不同年龄生物体通过异慢性异种共生或血浆的环境 调职。出乎意料的是，Wyss-Coray最近发现血浆中的热不稳定因子来自 年轻的小鼠或年轻的人类足以减缓或逆转小鼠的大脑衰老。相反， 老年小鼠或老年人类血浆中的因子可以加速大脑老化和 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 这促使怀斯-科雷博士从生理学的、自上而下的角度研究大脑老化。Dr。 Wyss-Coray正在使用化学、生物正交操作生物，尖端 蛋白质组学和下一代测序，以回答年轻血液如何重振老年人 分子水平上的大脑，并利用这些过程逆转与年龄相关的 人类大脑中的变化和阿尔茨海默氏症。这些研究的目标是开发 退伍军人和神经退行性疾病患者的新疗法。

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.