Department of General and Experimental Pathology, CEPT Laboratory, Medical University of Warsaw, ul. Pawińskiego 3C, 02-106 Warsaw, Poland.
Department of General and Experimental Pathology, CEPT Laboratory, Medical University of Warsaw, ul. Pawińskiego 3C, 02-106 Warsaw, Poland.
Ageing Res Rev. 2017 Nov;40:11-19. doi: 10.1016/j.arr.2017.08.001. Epub 2017 Aug 5.
Aging of organisms begins from a single cell at the molecular level. It includes changes related to telomere shortening, cell senescence and epigenetic modifications. These processes accumulate over the lifespan. Research studies show that epigenetic signaling contributes to human disease, tumorigenesis and aging. Epigenetic DNA modifications involve changes in the gene activity but not in the DNA sequence. An epigenome consists of chemical modifications to the DNA and histone proteins without the changes in the DNA sequence. These modifications strongly depend on the environment, could be reversible and are potentially transmittable to daughter cells. Epigenetics includes DNA methylation, noncoding RNA interference, and modifications of histone proteins. Sirtuins, a family of nicotine adenine dinucleotide (NAD+)-dependent enzymes, are involved in the cell metabolism and can regulate many cellular functions including DNA repair, inflammatory response, cell cycle or apoptosis. Literature shows the strong interconnection between sirtuin expression and aging processes. However, the direct relationship is still unknown. Here, we would like to summarize the existing knowledge about epigenetic processes in aging, especially those related to sirtuin expression. Another objective is to explain why some negative correlations between sirtuin activity and the rate of aging can be assumed.
生物体的衰老始于分子水平上的单个细胞。它包括与端粒缩短、细胞衰老和表观遗传修饰相关的变化。这些过程在整个生命周期中积累。研究表明,表观遗传信号参与了人类疾病、肿瘤发生和衰老。表观遗传 DNA 修饰涉及基因活性的变化,但不涉及 DNA 序列的变化。表观基因组由 DNA 和组蛋白的化学修饰组成,而不涉及 DNA 序列的变化。这些修饰强烈依赖于环境,可以是可逆的,并可能传递给子细胞。表观遗传学包括 DNA 甲基化、非编码 RNA 干扰和组蛋白的修饰。沉默调节蛋白(Sirtuins)是烟酰胺腺嘌呤二核苷酸(NAD+)依赖性酶家族,参与细胞代谢,可以调节许多细胞功能,包括 DNA 修复、炎症反应、细胞周期或细胞凋亡。文献表明,沉默调节蛋白表达与衰老过程之间存在强烈的相互关系。然而,直接的关系仍然未知。在这里,我们将总结衰老过程中表观遗传过程的现有知识,特别是与沉默调节蛋白表达相关的知识。另一个目的是解释为什么可以假设沉默调节蛋白活性与衰老速度之间存在一些负相关关系。