While aging is the greatest risk factor for the development of neurodegenerative disease, the role of aging in these diseases is poorly understood. In the inherited forms of these diseases, the disease-causing mutation is present from birth but symptoms appear decades later. This indicates that these mutations are well tolerated in younger individuals but not in older adults. Based on this observation, we hypothesized that changes taking place during normal aging make the cells in the brain (and elsewhere) susceptible to the disease-causing mutations. If so, then delaying some of these age-related changes may be beneficial in the treatment of neurodegenerative disease. In this review, we examine the effects of five compounds that have been shown to extend longevity (metformin, rapamycin, resveratrol, N-acetyl-l-cysteine, curcumin) in four of the most common neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis). While not all investigations observe a beneficial effect of these compounds, there are multiple studies that show a protective effect of each of these lifespan-extending compounds in animal models of neurodegenerative disease. Combined with genetic studies, this suggests the possibility that targeting the aging process may be an effective strategy to treat neurodegenerative disease.

虽然衰老是神经退行性疾病发展的最大风险因素，但人们对衰老在这些疾病中的作用知之甚少。在这些疾病的遗传形式中，致病突变从出生时就存在，但症状在几十年后出现。这表明这些突变在年轻人中具有良好的耐受性，但在老年人中则不然。基于这一观察，我们假设正常衰老过程中发生的变化使大脑（和其他地方）的细胞容易受到致病突变的影响。如果是这样，那么延迟一些与年龄相关的变化可能有利于神经退行性疾病的治疗。在这篇综述中，我们研究了五种已被证明可以延长寿命的化合物（二甲双胍、雷帕霉素、白藜芦醇、N-乙酰-L-半胱氨酸、姜黄素）对四种最常见的神经退行性疾病（阿尔茨海默病、帕金森病、亨廷顿舞蹈病、肌萎缩侧索硬化症）。虽然并非所有研究都观察到这些化合物的有益作用，但多项研究表明，这些延长寿命的化合物在神经退行性疾病动物模型中具有保护作用。结合遗传学研究，这表明针对衰老过程可能是治疗神经退行性疾病的有效策略。