The Metabolic Impact on Histone Acetylation and Transcription in Ageing.
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.
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. Electronic address: Shahafpeleg3@googlemail.com.
Shahaf
S
Peleg
Institute of Molecular Systems Biology, ETH Zürich, Auguste-Piccard-Hof 1, 8093 Zürich, Switzerland.
Christian
C
Feller
Biomedical Center, Department of Physiological Chemistry, Ludwig-Maximilians-Universität München, Großhaderner Strasse 9, 82152 Planegg-Martinsried, Germany; Center for Integrated Protein Science Munich (CIPSM), Ludwig-Maximilians-Universität München, Butenandt-Strasse 5, 81377 Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 17, 81377 Munich, Germany.
Andreas G
AG
Ladurner
Biomedical Center, Department of Molecular Biology, Ludwig-Maximilians-Universität München, Großhaderner Strasse 9, 82152 Planegg-Martinsried, Germany; Center for Integrated Protein Science Munich (CIPSM), Ludwig-Maximilians-Universität München, Butenandt-Strasse 5, 81377 Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 17, 81377 Munich, Germany; Biomedical Center, Protein Analysis Unit, Ludwig-Maximilians-Universität München, Großhaderner Strasse 9, 82152 Planegg-Martinsried, Germany. Electronic address: imhof@lmu.de.
Axel
A
Imhof
D000107:Acetylation; D000375:Aging / Q000235:genetics*; D000818:Animals; D006657:Histones / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D014158:Transcription, Genetic / Q000235:genetics*
D006657:Histones
aging; epigenetics; histone acetylation; metabolism; protein acetylation