SIRT1 controls circadian clock circuitry and promotes cell survival: a connection with age-related neoplasms
SIRT1 controls circadian clock circuitry and promotes cell survival: a connection with age-related neoplasms
复制标题
DOI：
10.1096/fj.09-129148
复制
发表时间：
2009-09-01
期刊：
影响因子：
4.8
通讯作者：
Ahmad, Nihal
中科院分区：
文献类型：
--
作者：
Jung-Hynes, Brittney;Ahmad, Nihal
衰老被认为是癌症的主要危险因素。有趣的是，III类组蛋白去乙酰化酶（hdac）的sirtuin家族与长寿的调节有关，并且可能是衰老和癌症之间缺失的联系。SIRT1是一种烟酰胺腺嘌呤二核苷酸（NAD(+)）依赖的sirtuin，已被证明通过抑制哺乳动物细胞凋亡或细胞衰老来促进细胞存活。最近的研究提供了SIRT1的细胞代谢功能和昼夜节律（由时钟机械控制）之间的联系，如果不加以控制，可能会导致某些癌症的风险增加。有趣的是，松果体褪黑激素（一种已知的昼夜节律调节器）的丧失已被证明会导致昼夜节律机制的失调和对癌症的易感性增加。在科学证据的基础上，我们提出了一个假设，即SIRT1抑制将通过在细胞水平上解除调控的核心时钟电路的再同步，在与年龄相关的癌症中赋予抗增殖反应。如果这一假设被证明是有效的，它可能最终导致开发新的方法来管理与年龄相关的恶性肿瘤和可能的其他疾病。-Jung-Hynes， B., Ahmad， N. SIRT1控制生物钟电路并促进细胞存活：与年龄相关肿瘤的联系。中国生物医学工程学报，23(2),391 - 391（2009）。www.fasebj.org
Aging is believed to be a primary risk factor for cancer. Interestingly, the sirtuin family of class III histone deacetylases (HDACs) has been implicated in the regulation of longevity and may be a lost link between aging and cancer. SIRT1, a nicotinamide adenine dinucleotide (NAD(+))-dependent sirtuin, has been shown to promote cell survival by inhibiting apoptosis or cellular senescence in mammalian cells. Recent studies have provided a link between the cellular metabolic function of SIRT1 and the circadian rhythm (controlled by a clock machinery), which, if deregulated, may lead to an increased risk for some cancers. Interestingly, the loss of the pineal hormone melatonin, a known regulator of circadian rhythm, has been shown to cause deregulation in the circadian rhythm machinery and an increase in susceptibility to cancer. On the basis of scientific evidence, we propose a hypothesis that SIRT1 inhibition will impart an anti-proliferative response in age-related cancers via resynchronization of deregulated core clock circuitry at the cellular level. If this hypothesis is found valid, it may ultimately lead to the development of novel approaches toward management of age-related malignancies and possibly other diseases.-Jung-Hynes, B., Ahmad, N. SIRT1 controls circadian clock circuitry and promotes cell survival: a connection with age-related neoplasms. FASEB J. 23, 2803-2809 (2009). www.fasebj.org