Longevity assurance interventions, metabolic health and Alzheimer's Disease

导致神经退行性变发病的年龄依赖性的机制是 未知，这是神经科学和生物老年学中的一个基本问题。 阿尔茨海默病(AD)是一种进行性神经退行性疾病，其特征是 痴呆症、β-淀粉样蛋白(A-β)斑块沉积和神经原纤维tau缠结。尽管 阿尔茨海默病对症缓解治疗的研究进展 边际收益，目前还不存在治愈方法。流行病学和临床前研究提供了 强有力的证据表明，包括肥胖、代谢综合征和2型在内的代谢紊乱 糖尿病是老年性疾病的主要危险因素，包括痴呆症和AD，但 其中涉及的机制仍有待阐明。 生长激素信号是新陈代谢和能量使用的中心调节器，它 通过荷尔蒙信号协调整个生物体的生理反应。 生长激素信号减弱的突变动物不仅寿命长，而且受到保护 与年龄相关的记忆力和学习能力下降。蛋氨酸限制已被证明 以前对大鼠和小鼠都有延长寿命和延缓衰老的作用，大大减少了身体 体重和肥胖，改善胰岛素敏感性和改善与衰老相关的改变 在血糖和血脂动态平衡方面。因此，延缓衰老模型与阿尔茨海默病相结合 表现出各种表型效应的模型为开发新的 模型将使研究重点放在衰老、新陈代谢和 神经退行性变。 我们建议的研究将确定是否抑制生长激素信号和蛋氨酸 限制将阻止行为、电生理和组织病理学的发展 AD表型异常可作为研究衰老与AD相互作用的模型。 为人类大脑在健康和疾病方面的分析提供了一个新的水平。

The mechanisms responsible for the age dependence of the onset of neurodegeneration are unknown, which represents a fundamental problem both in neuroscience and biogerontology. Alzheimer's disease (AD) is a progressive neurodegenerative condition characterized by dementia, deposition of beta amyloid (Aβ) plaques, and neurofibrillary tau tangles. Despite progress in developing treatments for the symptomatic relief of AD, most drugs only exhibit marginal benefits and no cure currently exists. Epidemiological and preclinical studies provide strong evidence that metabolic derangements including obesity, metabolic syndrome and type 2 diabetes constitute major risk factors for age-related diseases including dementia and AD but the mechanisms involved remain to be elucidated. The GH signaling functions as a central regulator of metabolism and energy use, and it coordinates the physiological responses of the entire organism through hormonal signaling. Mutant animals with reduced GH signaling are not only long-lived, but are protected against age-associated decline in memory and learning. Methionine restriction has been shown previously to extend lifespan and delay aging in both rats and mice, dramatically decrease body weight and adiposity, and improve insulin sensitivity and ameliorate aging-associated alterations in glucose and lipid homeostasis. Thus, combing delaying aging models with AD disease models exhibiting various phenotypic effects provides a novel opportunity to develop new models that will allow studies focused on the interaction between aging, metabolism, and neurodegeneration. Our proposed study will determine if suppression of the GH signaling and methionine restriction will prevent development of behavioral, electrophysiological and histopathologic abnormalities of AD phenotype can serve as a model to study the interaction of aging with AD, providing a new level of analysis of the human brain in health and disease.