Sirtuins, epigenetics and longevity

Abstract

Aging of organisms begins from a single cell at the molecular level. It includes changes related to telomere shortening, cell senescence and epigenetic modifications. These processes accumulate over the lifespan. Research studies show that epigenetic signaling contributes to human disease, tumorigenesis and aging. Epigenetic DNA modifications involve changes in the gene activity but not in the DNA sequence. An epigenome consists of chemical modifications to the DNA and histone proteins without the changes in the DNA sequence. These modifications strongly depend on the environment, could be reversible and are potentially transmittable to daughter cells. Epigenetics includes DNA methylation, noncoding RNA interference, and modifications of histone proteins. Sirtuins, a family of nicotine adenine dinucleotide (NAD+)-dependent enzymes, are involved in the cell metabolism and can regulate many cellular functions including DNA repair, inflammatory response, cell cycle or apoptosis. Literature shows the strong interconnection between sirtuin expression and aging processes. However, the direct relationship is still unknown. Here, we would like to summarize the existing knowledge about epigenetic processes in aging, especially those related to sirtuin expression. Another objective is to explain why some negative correlations between sirtuin activity and the rate of aging can be assumed.

Keywords: Aging; DNA; Epigenetics; Longevity; Sirtuins.