“Sirtuins”（保守的“依赖于NAD+-的去乙酰化酶”或ADP-核糖转移酶）有助于很多生物延长寿命，尽管其中所涉及的机制还很不清楚。例如，酵母sirtuin Sir2已知能够使组蛋白H4的赖氨酸 -16残迹脱去乙酰基，但不清楚这是否与Sir2的抗衰老功能有关。
现在，Dang等人报告了Sir2蛋白丰度与年龄相关的下降，这种下降与H4的赖氨酸 -16乙酰化和组蛋白的失去有关，使得从复制角度来讲比较老的酵母细胞中特定亚端粒区域转录沉默作用减弱。这一组蛋白乙酰化通道与关于酵母的现有衰老模型截然不同，可能代表着Sirtuins从演化角度来讲一个保守的功能，即通过使端粒染色质保持不变，来调控复制性衰老。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature 459, 802-807 (11 June 2009) | doi:10.1038/nature08085
Histone H4 lysine 16 acetylation regulates cellular lifespan
Weiwei Dang1, Kristan K. Steffen2, Rocco Perry1, Jean A. Dorsey1, F. Brad Johnson4, Ali Shilatifard5, Matt Kaeberlein3, Brian K. Kennedy2 & Shelley L. Berger1,6
1 Gene Expression and Regulation Program, The Wistar Institute Philadelphia, Pennsylvania 19104, USA
2 Department of Biochemistry,
3 Department of Pathology, University of Washington Seattle, Washington 98195, USA
4 Department of Pathology and Laboratory Medicine, Cell and Molecular Biology Group, Biomedical Graduate Studies and Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia 19104, Pennsylvania, USA
5 Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA
6 Department of Cell & Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Correspondence to: Shelley L. Berger1,6 Correspondence and requests for materials should be addressed to S.L.B.
Cells undergoing developmental processes are characterized by persistent non-genetic alterations in chromatin, termed epigenetic changes, represented by distinct patterns of DNA methylation and histone post-translational modifications. Sirtuins, a group of conserved NAD+-dependent deacetylases or ADP-ribosyltransferases, promote longevity in diverse organisms; however, their molecular mechanisms in ageing regulation remain poorly understood. Yeast Sir2, the first member of the family to be found, establishes and maintains chromatin silencing by removing histone H4 lysine 16 acetylation and bringing in other silencing proteins. Here we report an age-associated decrease in Sir2 protein abundance accompanied by an increase in H4 lysine 16 acetylation and loss of histones at specific subtelomeric regions in replicatively old yeast cells, which results in compromised transcriptional silencing at these loci. Antagonizing activities of Sir2 and Sas2, a histone acetyltransferase, regulate the replicative lifespan through histone H4 lysine 16 at subtelomeric regions. This pathway, distinct from existing ageing models for yeast, may represent an evolutionarily conserved function of sirtuins in regulation of replicative ageing by maintenance of intact telomeric chromatin.
