Zeng Li, Chen Rui, Liang Fengxia, Tsuchiya Hiroshi, Murai Hiroshi, Nakahashi Takeshi, Iwai Kunimitsu, Takahashi Takashi, Kanda Tsugiyasu, Morimoto Shigeto
Geriatric Medicine, Kanazawa Medical University, Kahoku-gun, Ishikawa, Japan.
Geriatr Gerontol Int. 2009 Mar;9(1):7-15. doi: 10.1111/j.1447-0594.2008.00504.x.
Sirtuin 1 (SIRT1), a member of the silent information regulator 2 in mammals, has recently been found to be involved in age-related diseases, such as cancer, metabolic diseases, cardiovascular disease, neurodegenerative diseases, osteoporosis and chronic obstructive pulmonary disease (COPD), mainly through deacetylation of substrates such as p53, forkhead box class O, peroxisome proliferator activated receptor gamma co-activator 1alpha, and nuclear factor-kappaB. It is widely reported that SIRT1 can promote not only carcinogenesis but also metastasis and insulin resistance, andhave beneficial effects in metabolic diseases, mediate high-density lipoprotein synthesis and regulate endothelial nitric oxide to protect against cardiovascular disease, have a cardioprotective role in heart failure, protect against neurodegenerative pathological changes, promote osteoblast differentiation, and also play a pivotal role as an anti-inflammatory mediator in COPD. However, there are controversial results suggesting that SIRT1 has an effect in protecting against DNA damage and accumulation of mutations, and preventing tumorigenesis. In addition, a high level of SIRT1 can induce cardiomyopathy and even heart failure. This article reviews recent developments relating to these issues.
沉默信息调节因子2（SIRT1）是哺乳动物沉默信息调节因子2家族的成员，最近发现它主要通过对p53、叉头框O类蛋白、过氧化物酶体增殖物激活受体γ共激活因子1α和核因子-κB等底物进行去乙酰化，参与癌症、代谢性疾病、心血管疾病、神经退行性疾病、骨质疏松症和慢性阻塞性肺疾病（COPD）等与年龄相关的疾病。广泛报道称，SIRT1不仅能促进肿瘤发生，还能促进转移和胰岛素抵抗，在代谢性疾病中具有有益作用，介导高密度脂蛋白合成并调节内皮型一氧化氮以预防心血管疾病，在心力衰竭中具有心脏保护作用，预防神经退行性病理变化，促进成骨细胞分化，并且在COPD中作为抗炎介质也起着关键作用。然而，也有一些有争议的结果表明，SIRT1在保护免受DNA损伤和突变积累以及预防肿瘤发生方面具有作用。此外，高水平的SIRT1可诱发心肌病甚至心力衰竭。本文综述了与这些问题相关的最新进展。
