Transcriptional repression of mitochondrial function in aging: a novel role for the silencing mediator of retinoid and thyroid hormone receptors co-repressor.
Transcriptional repression of mitochondrial function in aging: a novel role for the silencing mediator of retinoid and thyroid hormone receptors co-repressor.
复制标题
衰老过程中线粒体功能的转录抑制：类维生素A和甲状腺激素受体共阻遏物的沉默介质的新作用。
DOI：
10.1089/ars.2011.4413
复制
发表时间：
2013
影响因子：
6.6
通讯作者：
Lee,Chih-Hao
中科院分区：
文献类型：
--
作者：
Liu,Sihao;Reilly,ShannonM;Lee,Chih-Hao
意义：线粒体功能在代谢稳态中起重要作用，并与衰老有关。尽管关于线粒体来源的氧化应激是否导致衰老过程仍存在争议，但在动物模型中增加氧化代谢和抗氧化途径的干预措施可以防止与年龄相关的退化，如代谢性疾病和神经退行性疾病。最近的进展：已知的改善线粒体活性的转录网络之一是由转录共激活因子过氧化物酶体增殖体激活受体γ共激活因子1α (PGC-1α)介导的，它由amp激活的蛋白激酶（AMPK）和sirtuin 1 （SIRT1）激活，这两种主要的能量传感分子在某些模型系统中负责热量限制的长寿效应。PGC-1α共同激活几种核受体，特别是过氧化物酶体增殖物激活受体（PPAR）家族的成员，它们是线粒体氧化代谢的关键调节因子。关键问题：尽管AMPK/SIRT1-PGC-1α-PPAR轴在激活线粒体功能中发挥着重要作用，但其活性在老年动物中下调，提示在衰老过程中存在显性负调控机制。未来方向：在这篇综述中，我们将讨论转录共抑制因子的作用，类视黄醇和甲状腺激素受体（SMRT）的沉默介质，其活性和表达随着年龄的增长而增加，作为线粒体功能的负调节因子，促进衰老和年龄相关的代谢疾病。氧化还原信号学报，1999,19(2):444 - 444。
Significance:Mitochondrial function plays an important role in metabolic homeostasis and has been implicated in aging. Although there is still ongoing debate regarding whether mitochondrion-derived oxidative stress is causative to the aging process, interventions that increase oxidative metabolism and antioxidant pathways in animal models protect against age-related deterioration, such as metabolic diseases and neurodegenerative disorders.Recent Advances:One of the well-characterized transcriptional networks known to improve mitochondrial activity is mediated by transcriptional co-activator peroxisome proliferator-activated receptor gamma co-activator 1α (PGC-1α), which is activated by AMP-activated protein kinase (AMPK) and sirtuin 1 (SIRT1), two of the major energy sensing molecules that are responsible for the longevity effect of caloric restriction in certain model systems. PGC-1α co-activates several nuclear receptors, notably members of the peroxisome proliferator-activated receptor (PPAR) family, which are key regulators of mitochondrial oxidative metabolism.Critical Issues:Although the AMPK/SIRT1-PGC-1α-PPAR axis plays a prominent role in activating mitochondrial functions, their activities are down-regulated in older animals, suggesting the involvement of dominant negative regulatory mechanisms in the process of aging.Future Directions:In this review, we will discuss the role of a transcriptional co-repressor, silencing mediator of retinoid and thyroid hormone receptors (SMRT), whose activity and expression are increased with age, as a negative regulator of mitochondrial function that promotes aging and age-related metabolic diseases.Antioxid. Redox Signal.19, 299–309.