دانلود رایگان مقاله نقش sirtuins در پیری و بیماریهای مربوط به سن

Abstract

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.

3. Conclusion

The broad spectrum of processes in which sirtuins are involved suggests their possible role in the pathogenesis of many diseases, including the metabolic syndrome, neurodegenerative diseases, the inflammatory response, circulatory system diseases, neo- plasms, and other age-related diseases. Hence, the sirtuin activation can be a useful method of healthspan extension, or even of lifespan extension. There are two basic approaches to sirtuin activation. One of them is the use of exogenous activators (sirtuin-activating compounds; STACs), the other one is replenish- ment of the cellular NAD+ [20,173]. The first discovered exogenous SIRT1 activator was resveratrol [85,173]. A treatment with resveratrol and its derivatives allowed to achieve some beneficial effects of the SIRT1 induction without applying CR [174–176]. Following the discovery of resveratrol, a few researchers tried to find some selective activators – not only of SIRT1, but also of other sirtuins [176]. However, a more recent, and generally more useful approach involves using direct NAD+ precursors, such as the nicotinamide mononucleotide (NMN) or the nicotinamide ribose (NR) to replenish the cellular NAD+ [20].