Department of Dermatology, University of Wisconsin, Madison, WI 53706, USA.
J Pineal Res. 2010 Jan;48(1):9-19. doi: 10.1111/j.1600-079X.2009.00729.x.
Histone deacetylases (HDAC) have been under intense scientific investigation for a number of years. However, only recently the unique class III HDAC, sirtuins, have gained increasing investigational momentum. Originally linked to longevity in yeast, sirtuins and more specifically, SIRT1 have been implicated in numerous biological processes having both protective and/or detrimental effects. SIRT1 appears to play a critical role in the process of carcinogenesis, especially in age-related neoplasms. Similarly, alterations in circadian rhythms as well as production of the pineal hormone melatonin have been linked to aging and cancer risk. Melatonin has been found act as a differentiating agent in some cancer cells and to lower their invasive and metastatic status. In addition, melatonin synthesis and release occurs in a circadian rhythm fashion and it has been linked to the core circadian machinery genes (Clock, Bmal1, Periods, and Cryptochromes). Melatonin has also been associated with chronotherapy, the timely administration of chemotherapy agents to optimize trends in biological cycles. Interestingly, a recent set of studies have linked SIRT1 to the circadian rhythm machinery through direct deacetylation activity as well as through the nicotinamide adenine dinucleotide (NAD(+)) salvage pathway. In this review, we provide evidence for a possible connection between sirtuins, melatonin, and the circadian rhythm circuitry and their implications in aging, chronomodulation, and cancer.
组蛋白去乙酰化酶（HDAC）多年来一直是科学研究的热点。然而，直到最近，独特的 III 类 HDAC，即沉默调节蛋白（sirtuins），才引起了越来越多的研究兴趣。最初与酵母的长寿有关，sirtuins 特别是 SIRT1 已被牵连到许多具有保护和/或有害作用的生物学过程中。SIRT1 似乎在致癌过程中起着关键作用，尤其是在与年龄相关的肿瘤中。同样，昼夜节律的改变以及松果腺激素褪黑素的产生与衰老和癌症风险有关。褪黑素已被发现可在某些癌细胞中起分化作用，并降低其侵袭性和转移性。此外，褪黑素的合成和释放呈昼夜节律模式，与核心昼夜节律机制基因（Clock、Bmal1、Periods 和 Cryptochromes）有关。褪黑素还与时间治疗学有关，即定时给予化疗药物以优化生物周期的趋势。有趣的是，最近的一系列研究通过直接去乙酰化活性以及烟酰胺腺嘌呤二核苷酸（NAD(+)）回收途径将 SIRT1 与昼夜节律机制联系起来。在这篇综述中，我们提供了证据表明沉默调节蛋白、褪黑素和昼夜节律电路之间可能存在联系，以及它们在衰老、时间调控和癌症中的影响。
