From heterochromatin islands to the NAD World: a hierarchical view of aging through the functions of mammalian Sirt1 and systemic NAD biosynthesis.
From heterochromatin islands to the NAD World: a hierarchical view of aging through the functions of mammalian Sirt1 and systemic NAD biosynthesis.
复制标题
DOI：
10.1016/j.bbagen.2009.03.005
复制
发表时间：
2009-10
影响因子：
3
通讯作者：
Imai, Shin-ichiro
中科院分区：
文献类型：
--
作者：
Imai, Shin-ichiro
关键词：
在过去的几十年里，衰老科学一直在迅速发展，强大的遗传工具已经确定了各种进化保守的调节因子和信号通路，以控制模式生物的衰老和寿命。然而，一个巨大的挑战仍然是构建一个全面的概念，将许多不同层次的生物事件整合到一个系统的、分层的衰老观点中。“异染色质岛”假说最初是在10年前提出的，用于解释细胞和生物体衰老的确定性和随机性，这促使作者对进化上保守的Sir2蛋白进行研究。自从令人惊讶地发现它们的nad依赖性去乙酰化酶活性以来，Sir2蛋白，现在被称为“sirtuins”，已经成为衰老的关键表观遗传调节剂。在这篇综述中，我将遵循概念发展的过程，从异染色质岛假说到一个新的、全面的哺乳动物衰老系统调节网络的概念，称为“NAD世界”，总结了哺乳动物NAD依赖的去乙酰化酶Sirt1和烟酰胺磷酸核糖基转移酶（Nampt）介导的系统性NAD生物合成的最新研究。NAD世界的新概念为从根本上连接新陈代谢和衰老的系统调节机制提供了重要的见解，并传达了哺乳动物衰老调节的功能等级和脆弱性的思想。
For the past couple of decades, aging science has been rapidly evolving, and powerful genetic tools have identified a variety of evolutionarily conserved regulators and signaling pathways for the control of aging and longevity in model organisms. Nonetheless, a big challenge still remains to construct a comprehensive concept that could integrate many distinct layers of biological events into a systemic, hierarchical view of aging. The “heterochromatin island” hypothesis was originally proposed 10 years ago to explain deterministic and stochastic aspects of cellular and organismal aging, which drove the author to the study of evolutionarily conserved Sir2 proteins. Since a surprising discovery of their NAD-dependent deacetylase activity, Sir2 proteins, now called “sirtuins,” have been emerging as a critical epigenetic regulator for aging. In this review, I will follow the process of conceptual development from the heterochromatin island hypothesis to a novel, comprehensive concept of a systemic regulatory network for mammalian aging, named “NAD World,” summarizing recent studies on the mammalian NAD-dependent deacetylase Sirt1 and nicotinamide phosphoribosyltransferase (Nampt)-mediated systemic NAD biosynthesis. This new concept of the NAD World provides critical insights into a systemic regulatory mechanism that fundamentally connects metabolism and aging and also conveys the ideas of functional hierarchy and frailty for the regulation of aging in mammals.
登录
查看更多内容
影响因子：
9.8
作者：
Bordone L;Motta MC;Picard F;Robinson A;Jhala US;Apfeld J;McDonagh T;Lemieux M;McBurney M;Szilvasi A;Easlon EJ;Lin SJ;Guarente L
通讯作者：
Guarente L
影响因子：
10.5
作者：
BRACHMANN, CB;SHERMAN, JM;BOEKE, JD
通讯作者：
BOEKE, JD
影响因子：
11.8
作者：
Fulco, Marcella;Cen, Yana;Sartorelli, Vittorio
通讯作者：
Sartorelli, Vittorio
影响因子：
29
作者：
Banks AS;Kon N;Knight C;Matsumoto M;Gutiérrez-Juárez R;Rossetti L;Gu W;Accili D
通讯作者：
Accili D
影响因子：
64.8
作者：
Anderson, RM;Bitterman, KJ;Sinclair, DA
通讯作者：
Sinclair, DA