SIRTUIN家族包括7种NAD+依赖性酶（SIRT1-7），被公认为III类组蛋白脱乙酰基酶（HDACS）。自从SIR2的同源物被证明在酵母中具有抗衰老功能以来，他们逐渐达到了名人身份。但是，哺乳动物的sirtuins在抗衰老蛋白中占有重要地位，还是仅仅是另一个随行人员？
衰老定义为细胞的功能和生理下降，部分与DNA完整性和基因组稳定性降低有关。SIRT1是SIRT家族的原始成员，首先据报道保持端粒长度并调节DNA损伤修复。之后，人们揭露了SIRT1和其他成员主要通过脱乙酰化来修饰染色质和调节DNA修复因子的活性，与DNA损伤反应有关。除了它们在DNA修复中的作用，它们最近在人类衰老相关病理（例如代谢综合征和肿瘤发生）的细胞过程中发现。
Sirtuins are involved in many aspects of glucose and lipid homeostasis.
Metabolic syndrome is characterized as a combination of obesity, inflammation, high blood pressure and dyslipidemia. The major culprit for this disorder is the excessive calorie intake. Calorie restriction (CR), therefore, lies at the opposite ends of the same spectrum. CR was first described as a reduction in food intake in laboratory rodents that would partly extend their lifespan. It now seems that the salutary effects of CR may improve the physiological parameters in metabolic syndrome and protect against many diseases in rodents including cardiovascular disease and diabetes.
Further, it is proposed that metabolic syndrome and CR are mediated through the same set of regulators and sirtuins may be essentially required in their induced effects. Indeed, sirtuins are involved in many aspects of glucose and lipid homeostasis. Most sirtuins are reported to promote gluconeogenesis in liver, fatty acid oxidation in muscle, fatty acid mobilization in adipose tissues and enhance insulin secretion in pancreas. It is reasonable to believe that the metabolic activities of sirtuins may mimic the CR state and ameliorate several metabolic diseases.
Besides metabolic disorders, tumorigenesis is also a time-dependent process associated with ageing. Genomic instability and metabolic reprogramming are two characteristic hallmarks in cancer. Considering their pivotal roles in DNA repair and cellular metabolism, sirtuins are characterized as context-dependent tumor suppressor and/or oncogene. Nuclear sirtuins (SIRT1, SIRT6) may protect host cells from tumorigenesis by positively triggering DNA repair. But when they enhance genome integrity in tumor cells such as SIRT7, their roles are considered to be oncogenic.
核SIRTUIN（SIRT1，SIRT6）可以通过积极触发DNA修复来保护宿主细胞免受肿瘤发生。
Elevated aerobic glycolysis and extensive glutaminolysis are commonly found in most cancer cells. After their inhibitory roles in aerobic glycolysis were reported, sirtuins’ implication in glutamine metabolism attracted considerable attention. Glutamine metabolism is proposed to drive tumor growth by providing a ready source of carbon and nitrogen to support biomass synthesis and cellular homeostasis. It is uncovered that SIRT4 (one of mitochondrial sirtuins) elicits the inhibition of glutamine metabolism and an attendant halt of cell proliferation that provides opportunity for DNA damage repair, which spurred the hypothesis that sirtuins may coordinate genomic instability and aberrant cellular metabolism in cancer cells.
充当肿瘤抑制剂和/或癌基因，这些Sirtuins的特定活化剂或抑制剂的发展可能为各种类型的癌症提供治疗机会。在当前的临床前试验中，SIRT1和SIRT2的抑制剂似乎很有希望。例如，抑制剂西替诺诱导生长停滞，并增强对人乳腺癌细胞，肺癌细胞和白血病细胞化疗药物的敏感性。剑桥醇已被证明可以防止伯基特淋巴瘤的生长。
Clearly, there is much more to be learned about sirtuins and ageing-related pathologies (metabolic syndrome and tumorigenesis), but it is likely that sirtuins will have important roles in future therapy of these diseases.
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