Glenn Laboratories for the Molecular Biology of Aging, Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Annu Rev Pathol. 2010;5:253-95. doi: 10.1146/annurev.pathol.4.110807.092250.
Aging is accompanied by a decline in the healthy function of multiple organ systems, leading to increased incidence and mortality from diseases such as type II diabetes mellitus, neurodegenerative diseases, cancer, and cardiovascular disease. Historically, researchers have focused on investigating individual pathways in isolated organs as a strategy to identify the root cause of a disease, with hopes of designing better drugs. Studies of aging in yeast led to the discovery of a family of conserved enzymes known as the sirtuins, which affect multiple pathways that increase the life span and the overall health of organisms. Since the discovery of the first known mammalian sirtuin, SIRT1, 10 years ago, there have been major advances in our understanding of the enzymology of sirtuins, their regulation, and their ability to broadly improve mammalian physiology and health span. This review summarizes and discusses the advances of the past decade and the challenges that will confront the field in the coming years.
衰老是伴随着多个器官系统的健康功能下降而发生的，导致 2 型糖尿病、神经退行性疾病、癌症和心血管疾病等疾病的发病率和死亡率增加。从历史上看，研究人员一直专注于研究孤立器官中的单个途径，作为一种确定疾病根源的策略，以期设计出更好的药物。对酵母衰老的研究导致了一类被称为 sirtuins 的保守酶的发现，这些酶影响着多种途径，从而延长了生物体的寿命和整体健康。自 10 年前发现第一个已知的哺乳动物 sirtuin（SIRT1）以来，我们对 sirtuins 的酶学、调节及其广泛改善哺乳动物生理学和健康跨度的能力有了重大的理解进展。本综述总结和讨论了过去十年的进展，以及未来几年该领域将面临的挑战。
