“Sirtuins”（保守的“依賴于NAD+-的去乙?；?rdquo;或ADP-核糖轉(zhuǎn)移酶）有助于很多生物延長壽命，盡管其中所涉及的機制還很不清楚,。例如,，酵母sirtuin Sir2已知能夠使組蛋白H4的賴氨酸 -16殘跡脫去乙酰基,，但不清楚這是否與Sir2的抗衰老功能有關(guān),。
現(xiàn)在，Dang等人報告了Sir2蛋白豐度與年齡相關(guān)的下降,，這種下降與H4的賴氨酸 -16乙?；徒M蛋白的失去有關(guān)，使得從復(fù)制角度來講比較老的酵母細(xì)胞中特定亞端粒區(qū)域轉(zhuǎn)錄沉默作用減弱,。這一組蛋白乙?；ǖ琅c關(guān)于酵母的現(xiàn)有衰老模型截然不同，可能代表著Sirtuins從演化角度來講一個保守的功能,，即通過使端粒染色質(zhì)保持不變,，來調(diào)控復(fù)制性衰老。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
