The sirtuin family's role in aging and age-associated pathologies

Abstract

The 7 mammalian sirtuin proteins compose a protective cavalry of enzymes that can be invoked by cells to aid in the defense against a vast array of stressors. The pathologies associated with aging, such as metabolic syndrome, neurodegeneration, and cancer, are either caused by or exacerbated by a lifetime of chronic stress. As such, the activation of sirtuin proteins could provide a therapeutic approach to buffer against chronic stress and ameliorate age-related decline. Here we review experimental evidence both for and against this proposal, as well as the implications that isoform-specific sirtuin activation may have for healthy aging in humans.

Figure 1. Anticipated effect of isoform-specific sirtuin activation on various age-related diseases.

Based on the current literature, this figure depicts the potential outcomes associated with individual sirtuin activation (SIRT1–7). The sirtuin isoforms with substantial data indicating either a protective or aggravative role for specific age-related diseases are indicated. There are specific disease states in which there is significant uncertainty in the literature as to whether activation or inhibition of the sirtuin is more beneficial, and these instances are thus classified as “disputed.” In the case of cancer, the tumor-suppressor role of certain sirtuin proteins is dependent on cell and tissue type.