Role of Sirtuins in Maintenance of Genomic Stability: Relevance to Cancer and Healthy Aging.

Abstract

Genomic instability and epigenetic alterations are distinct hallmarks shared by cancer and aging. Sirtuins (SIRTs) are class III histone deacetylases that regulate gene expression in response to cellular metabolic status. SIRTs can modulate chromatin function through direct deacetylation of histones and by promoting altered methylation of histones and DNA, leading to repression of transcription. They can also interact and deacetylate a broad range of transcription factors and coregulators, thereby regulating target gene expression both positively and negatively. SIRT inhibition may be beneficial in decreasing the risk of some cancers, while SIRT activation can exert positive antiaging effects and help prevent age-related disease and cancers. Thus, SIRT modulation may positively affect the treatment of cancer and age-related disorders. In this study, we review emerging data on the effects of SIRTs as important regulators of genomic stability and explain the biological roles of SIRTs in cancer and aging.