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Age reprogramming and epigenetic rejuvenation

机译:年龄重编程和表观遗传复兴

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摘要

Age reprogramming represents a novel method for generating patient-specific tissues for transplantation. It bypasses the de-differentiation/redifferentiation cycle that is characteristic of the induced pluripotent stem (iPS) and nuclear transfer-embryonic stem (NT-ES) cell technologies that drive current interest in regenerative medicine. Despite the obvious potential of iPS and NT-ES cell-based therapies, there are several problems that must be overcome before these therapies are safe and routine. As an alternative, age reprogramming aims to rejuvenate the specialized functions of an old cell without de-differentiation; age reprogramming does not require developmental reprogramming through an embryonic stage, unlike the iPS and NT-ES cell-based therapies. Tests of age reprogramming have largely focused on one aspect, the epigenome. Epigenetic rejuvenation has been achieved in vitro in the absence of de-differentiation using iPS cell reprogramming factors. Studies on the dynamics of epigenetic age (eAge) reprogramming have demonstrated that the separation of eAge from developmental reprogramming can be explained largely by their different kinetics. Age reprogramming has also been achieved in vivo and shown to increase lifespan in a premature ageing mouse model. We conclude that age and developmental reprogramming can be disentangled and regulated independently in vitro and in vivo.
机译:年龄重新编程代表了一种用于生成患者特定组织进行移植的新颖方法。它绕过了诱导分化的多能干细胞(iPS)和核移植胚胎干细胞(NT-ES)细胞技术所特有的去分化/再分化周期,这些技术推动了人们对再生医学的兴趣。尽管基于iPS和NT-ES细胞的治疗方法具有明显的潜力,但在安全和常规治疗之前必须克服一些问题。另一种选择是,年龄重编程旨在恢复旧细胞的特殊功能而不会去分化。与基于iPS和NT-ES细胞的疗法不同,年龄重新编程不需要整个胚胎阶段的发育重新编程。年龄重编程的测试主要集中在一方面,表观基因组。使用iPS细胞重编程因子,在不存在去分化的情况下,已经在体外实现了表观遗传的复兴。对表观遗传年龄(eAge)重编程动力学的研究表明,eAge与发育重编程的分离可以很大程度上由其不同的动力学来解释。体内年龄重编程也已经实现,并显示出可在早衰小鼠模型中延长寿命。我们得出的结论是,年龄和发育的重编程可以在体外和体内独立进行纠缠和调节。

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