Department of Biology, Texas A&M University, College Station, Texas, USA.
Department of Medical Genetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Cell Reprogram. 2024 Feb;26(1):10-23. doi: 10.1089/cell.2023.0123.
Aging causes numerous age-related diseases, leading the human species to death. Nevertheless, rejuvenating strategies based on cell epigenetic modifications are a possible approach to counteract disease progression while getting old. Cell reprogramming of adult somatic cells toward pluripotency ought to be a promising tool for age-related diseases. However, researchers do not have control over this process as cells lose their fate, and cause potential cancerous cells or unexpected cell phenotypes. Direct and partial reprogramming were introduced in recent years with distinctive applications. Although direct reprogramming makes cells lose their identity, it has various applications in regeneration medicine. Temporary and regulated overexpression of Yamanaka factors has been shown in several experimental contexts to be achievable and is used to rejuvenate mice models. This regeneration can be accomplished by altering the epigenetic adult cell signature to the signature of a younger cell. The greatest advantage of partial reprogramming is that this method does not allow cells to lose their identity when they are resetting their epigenetic clock. It is a regimen of short-term Oct3/4, Sox2, Klf4, and c-Myc expression that prevents full reprogramming to the pluripotent state and avoids both tumorigenesis and the presence of unwanted undifferentiated cells. We know that many neurological age-related diseases, such as Alzheimer's disease, stroke, dementia, and Parkinson's disease, are the main cause of death in the last decades of life. Therefore, scientists have a special tendency regarding neuroregeneration methods to increase human life expectancy.
衰老是许多与年龄相关疾病的主要原因，导致人类死亡。然而，基于细胞表观遗传修饰的抗衰老策略可能是一种对抗疾病进展的方法。将成年体细胞重编程为多能性细胞应该是治疗与年龄相关疾病的有前途的方法。然而，由于细胞失去了其命运，并且可能导致潜在的癌细胞或意外的细胞表型，因此研究人员无法控制这个过程。近年来，直接和部分重编程被引入，具有独特的应用。虽然直接重编程使细胞失去了其身份，但它在再生医学中有多种应用。在几个实验背景下，已经证明可以临时和调节过表达 Yamanaka 因子，并用于使小鼠模型年轻化。这种再生可以通过改变成年细胞的表观遗传特征来实现，使其类似于年轻细胞的特征。部分重编程的最大优点是，当细胞重置其表观遗传时钟时，这种方法不会允许细胞失去其身份。这是一种短期表达 Oct3/4、Sox2、Klf4 和 c-Myc 的方案，可以防止完全重编程为多能状态，并避免肿瘤形成和出现不需要的未分化细胞。我们知道，许多神经退行性疾病，如阿尔茨海默病、中风、痴呆和帕金森病，是生命最后几十年死亡的主要原因。因此，科学家们对神经再生方法有一种特殊的倾向，以延长人类的预期寿命。
