McGuinness D, McGuinness D H, McCaul J A, Shiels P G
College of Medical, Veterinary and Life Sciences, Institute of Cancer Sciences, University of Glasgow, Glasgow G11 6NT, Scotland, UK.
J Aging Res. 2011;2011:235754. doi: 10.4061/2011/235754. Epub 2011 Jun 30.
The Sirtuins are a family of orthologues of yeast Sir2 found in a wide range of organisms from bacteria to man. They display a high degree of conservation between species, in both sequence and function, indicative of their key biochemical roles. Sirtuins are heavily implicated in cell cycle, cell division, transcription regulation, and metabolism, which places the various family members at critical junctures in cellular metabolism. Typically, Sirtuins have been implicated in the preservation of genomic stability and in the prolongation of lifespan though many of their target interactions remain unknown. Sirtuins play key roles in tumourigenesis, as some have tumour-suppressor functions and others influence tumours through their control of the metabolic state of the cell. Their links to ageing have also highlighted involvement in various age-related and degenerative diseases. Here, we discuss the current understanding of the role of Sirtuins in age-related diseases while taking a closer look at their roles and functions in maintaining genomic stability and their influence on telomerase and telomere function.
沉默调节蛋白是在从细菌到人类等广泛生物体中发现的酵母Sir2的直系同源物家族。它们在物种间的序列和功能上都表现出高度的保守性,这表明了它们关键的生化作用。沉默调节蛋白与细胞周期、细胞分裂、转录调控和代谢密切相关,这使得各个家族成员处于细胞代谢的关键节点。通常,沉默调节蛋白与基因组稳定性的维持和寿命的延长有关,尽管它们的许多靶点相互作用仍不为人知。沉默调节蛋白在肿瘤发生中起关键作用,因为一些具有肿瘤抑制功能,而另一些则通过控制细胞的代谢状态影响肿瘤。它们与衰老的联系也凸显了它们参与各种与年龄相关的退行性疾病。在这里,我们讨论目前对沉默调节蛋白在与年龄相关疾病中的作用的理解,同时更深入地探讨它们在维持基因组稳定性中的作用和功能,以及它们对端粒酶和端粒功能的影响。