Biomedical Center, Department of Physiological Chemistry, Ludwig-Maximilians-Universität München, Großhaderner Strasse 9, 82152 Planegg-Martinsried, Germany; Biomedical Center, Department of Molecular Biology, Ludwig-Maximilians-Universität München, Großhaderner Strasse 9, 82152 Planegg-Martinsried, Germany.
Institute of Molecular Systems Biology, ETH Zürich, Auguste-Piccard-Hof 1, 8093 Zürich, Switzerland.
Trends Biochem Sci. 2016 Aug;41(8):700-711. doi: 10.1016/j.tibs.2016.05.008. Epub 2016 Jun 7.
Loss of cellular homeostasis during aging results in altered tissue functions and leads to a general decline in fitness and, ultimately, death. As animals age, the control of gene expression, which is orchestrated by multiple epigenetic factors, degenerates. In parallel, metabolic activity and mitochondrial protein acetylation levels also change. These two hallmarks of aging are effectively linked through the accumulating evidence that histone acetylation patterns are susceptible to alterations in key metabolites such as acetyl-CoA and NAD(+), allowing chromatin to function as a sensor of cellular metabolism. In this review we discuss experimental data supporting these connections and provide a context for the possible medical and physiological relevance.
衰老过程中细胞内稳态的丧失导致组织功能改变,并导致适应能力的普遍下降,最终导致死亡。随着动物年龄的增长,由多种表观遗传因素协调的基因表达控制逐渐衰退。与此同时,代谢活性和线粒体蛋白乙酰化水平也发生变化。这两个衰老的特征通过越来越多的证据有效地联系在一起,这些证据表明组蛋白乙酰化模式易受关键代谢物(如乙酰辅酶 A 和 NAD(+))的改变的影响,从而使染色质能够作为细胞代谢的传感器发挥作用。在这篇综述中,我们讨论了支持这些联系的实验数据,并为其可能的医学和生理学相关性提供了背景。