Wątroba Mateusz, Szukiewicz Dariusz
Department of General & Experimental Pathology with Centre for Preclinical Research and Technology (CEPT), Medical University of Warsaw, Warsaw, Poland.
Department of General & Experimental Pathology with Centre for Preclinical Research and Technology (CEPT), Medical University of Warsaw, Warsaw, Poland.
Adv Med Sci. 2016 Mar;61(1):52-62. doi: 10.1016/j.advms.2015.09.003. Epub 2015 Sep 26.
Sirtuins, initially described as histone deacetylases and gene silencers in yeast, are now known to have much more functions and to be much more abundant in living organisms. Sirtuins gained much attention when they were first acknowledged to be responsible for some beneficial and longevity-promoting effects of calorie restriction in many species of animals - from fruit flies to mammals. In this paper, we discuss some detailed molecular mechanisms of inducing these effects, and wonder if they could be possibly mimicked without actually applying calorie restriction, through induction of sirtuin activity. It is known now that sirtuins, when adjusting the pattern of cellular metabolism to nutrient availability, can regulate many metabolic functions significant from the standpoint of aging research - including DNA repair, genome stability, inflammatory response, apoptosis, cell cycle, and mitochondrial functions. While carrying out these regulations, sirtuins cooperate with many transcription factors, including PGC-1a, NFKB, p53 and FoxO. This paper contains some considerations about possible use of facilitating activity of the sirtuins in prevention of aging, metabolic syndrome, chronic inflammation, and other diseases.
沉默调节蛋白最初被描述为酵母中的组蛋白脱乙酰酶和基因沉默子,现在已知它们具有更多功能,并且在生物体中更为丰富。当沉默调节蛋白首次被认为是许多动物物种(从果蝇到哺乳动物)中热量限制的一些有益和促进长寿作用的原因时,它们受到了广泛关注。在本文中,我们讨论了诱导这些作用的一些详细分子机制,并思考是否可以通过诱导沉默调节蛋白活性,在不实际应用热量限制的情况下模拟这些作用。现在已知,沉默调节蛋白在根据营养物质可用性调整细胞代谢模式时,可以调节许多从衰老研究角度来看很重要的代谢功能——包括DNA修复、基因组稳定性、炎症反应、细胞凋亡、细胞周期和线粒体功能。在执行这些调节时,沉默调节蛋白与许多转录因子合作,包括PGC-1α、NF-κB、p53和FoxO。本文包含了一些关于利用沉默调节蛋白活性预防衰老、代谢综合征、慢性炎症和其他疾病的可能性的思考。