Sirtuins, melatonin and circadian rhythms: building a bridge between aging and cancer.
Sirtuins, melatonin and circadian rhythms: building a bridge between aging and cancer.
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DOI：
10.1111/j.1600-079x.2009.00729.x
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发表时间：
2010-01
影响因子：
10.3
通讯作者：
Ahmad N
中科院分区：
文献类型：
--
作者：
Jung-Hynes B;Reiter RJ;Ahmad N
组蛋白去乙酰化酶（HDAC）多年来一直处于密集的科学研究之下。然而，直到最近，独特的III类HDAC，sirtuins，已经获得了越来越多的研究势头。最初与酵母中的长寿有关，sirtuins，更具体地说，SIRT 1涉及许多具有保护和/或有害作用的生物过程。SIRT 1似乎在癌症发生过程中起关键作用，特别是在年龄相关的肿瘤中。同样，昼夜节律的改变以及松果体激素褪黑激素的产生与衰老和癌症风险有关。褪黑激素在某些癌细胞中起分化剂的作用，并降低其侵袭和转移状态。此外，褪黑激素的合成和释放以昼夜节律的方式发生，并且它与核心昼夜节律机制基因（Clock，Bmal 1，Periods和Cryptochromes）有关。褪黑激素也与时间疗法有关，时间疗法是指及时给予化疗药物以优化生物周期的趋势。有趣的是，最近的一组研究将SIRT 1通过直接脱乙酰活性以及通过NAD+补救途径与昼夜节律机制联系起来。在这篇综述中，我们提供的证据sirtuins，褪黑激素和昼夜节律电路之间可能存在联系，并在衰老，时间调节和癌症的影响。
Histone deacetylases (HDACs) have been under intense scientific investigation for a number of years. However, only recently the unique class III HDACs, 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 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.