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 mitochondria! 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.