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Aging in a Dish: iPSC-Derived and Directly Induced Neurons for Studying Brain Aging and Age-Related Neurodegenerative Diseases
Annual Review of Genetics ( IF 8.7 ) Pub Date : 2018-11-26 00:00:00 , DOI: 10.1146/annurev-genet-120417-031534
Jerome Mertens 1, 2 , Dylan Reid 1 , Shong Lau 1 , Yongsung Kim 1 , Fred H. Gage 1
Affiliation  

Age-associated neurological diseases represent a profound challenge in biomedical research as we are still struggling to understand the interface between the aging process and the manifestation of disease. Various pathologies in the elderly do not directly result from genetic mutations, toxins, or infectious agents but are primarily driven by the many manifestations of biological aging. Therefore, the generation of appropriate model systems to study human aging in the nervous system demands new concepts that lie beyond transgenic and drug-induced models. Although access to viable human brain specimens is limited and induced pluripotent stem cell models face limitations due to reprogramming-associated cellular rejuvenation, the direct conversion of somatic cells into induced neurons allows for the generation of human neurons that capture many aspects of aging. Here, we review advances in exploring age-associated neurodegenerative diseases using human cell reprogramming models, and we discuss general concepts, promises, and limitations of the field.

中文翻译:


衰老:iPSC衍生和直接诱导的神经元,用于研究脑衰老和与年龄有关的神经退行性疾病

与年龄相关的神经系统疾病在生物医学研究中代表着巨大的挑战,因为我们仍在努力理解衰老过程与疾病表现之间的关系。老年人的各种病理并非直接由遗传突变,毒素或传染原引起,而是主要由生物衰老的许多表现所驱动。因此,产生合适的模型系统来研究人类在神经系统中的衰老需要新的概念,而这些概念不只是转基因和药物诱导的模型。尽管获得可行的人类脑标本的途径受到限制,并且由于与编程相关的细胞复兴,诱导型多能干细胞模型仍面临局限性,体细胞直接转化为诱导的神经元可以产生捕获衰老许多方面的人类神经元。在这里,我们回顾了使用人类细胞重编程模型探索与年龄相关的神经退行性疾病的进展,并讨论了该领域的一般概念,前景和局限性。

更新日期:2018-11-26
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