Lifespan extension, Somatotropic signaling and Tauopathy

Tauopathies是一类神经退行性疾病，其特征在于Tau蛋白的积累。 脑中异常和过度磷酸化的tau蛋白，包括阿尔茨海默病（AD）， 帕金森病（PD）、额颞叶痴呆（FTD）和运动神经元病（MND）。 Tau病主要发生在老年人群中，发病率随着年龄的增长而上升。 不幸的是，tau蛋白病的年龄依赖性发作的机制是未知的， 没有有效的治疗策略。衰老是tau蛋白病的最大风险因素 相关疾病，这表明分子改变有助于衰老过程， 代表了tau病理学的共同机制。利用这些途径可以减缓或 延缓衰老过程可能为新的治疗策略提供新的靶点。 具有缓慢老化速率的鼠突变小鼠和具有不同老化速率的鼠tau蛋白病模型 表型效应为开发新的遗传模型提供了机会， 研究衰老和tau蛋白病的相互作用。我们的建议是阐明 在年龄依赖性的tau蛋白病易感性的生长激素轴。我们的研究将产生 新的模型，以研究衰老与神经退行性疾病的相互作用， 减缓衰老过程的突变

Tauopathies are a class of neurodegenerative diseases characterized by accumulation of abnormal and hyperphosphorylated tau protein in the brain including Alzheimer's disease (AD), Parkinson's disease (PD), Frontotemporal dementia (FTD), and Motor Neuron Disease (MND). Tauopathies occur primarily in elderly population and incidence rises with increasing age. Unfortunately, the mechanisms for the age-dependent onset of tauopathies are unknown and there are no effective therapeutic strategy. Aging is the biggest risk factor for tauopathies related disorders, suggesting that molecular alterations contributing to the aging process may represent common mechanisms for tau pathology. Employing the pathways that could slow or delay the aging process may offer novel targets for new therapeutic strategies. Murine mutant mice with slow rates of aging and murine tauopathy models with varying phenotypic effects provide the opportunity to develop novel genetic models that will allow studying the interaction of aging and tauopathy. Our proposal is to elucidate the role of the somatotropic axis in the age-dependent susceptibility to tauopathies. Our study will generate new models to study the interaction of aging with neurodegenerative diseases in the context of mutations that slow the aging process.