Department of Obstetrics & Gynecology, Stanford School of Medicine, Stanford University, Stanford, CA, USA.
Institute for Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, USA.
Nat Aging. 2024 Jan;4(1):14-26. doi: 10.1038/s43587-023-00539-2. Epub 2023 Dec 15.
Over the past decade, there has been a dramatic increase in efforts to ameliorate aging and the diseases it causes, with transient expression of nuclear reprogramming factors recently emerging as an intriguing approach. Expression of these factors, either systemically or in a tissue-specific manner, has been shown to combat age-related deterioration in mouse and human model systems at the cellular, tissue and organismal level. Here we discuss the current state of epigenetic rejuvenation strategies via partial reprogramming in both mouse and human models. For each classical reprogramming factor, we provide a brief description of its contribution to reprogramming and discuss additional factors or chemical strategies. We discuss what is known regarding chromatin remodeling and the molecular dynamics underlying rejuvenation, and, finally, we consider strategies to improve the practical uses of epigenetic reprogramming to treat aging and age-related diseases, focusing on the open questions and remaining challenges in this emerging field.
在过去的十年中，人们在改善衰老及其引发的疾病方面做出了巨大的努力，其中瞬时表达核重编程因子最近成为一种引人关注的方法。这些因子的表达，无论是全身性的还是组织特异性的，都已被证明可以在细胞、组织和机体水平上对抗与年龄相关的小鼠和人类模型系统的恶化。在这里，我们讨论了通过在小鼠和人类模型中部分重编程实现表观遗传再年轻化的当前策略。对于每个经典的重编程因子，我们简要描述了其对重编程的贡献，并讨论了其他因子或化学策略。我们讨论了关于染色质重塑和再年轻化的分子动力学的已知内容，最后，我们考虑了改善表观遗传重编程在治疗衰老和与年龄相关疾病中的实际应用的策略，重点关注这一新兴领域中的悬而未决的问题和剩余挑战。
