SIRT6

Sirtuin-6 (SIRT6) is a stress responsive protein deacetylase and mono-ADP ribosyltransferase is_associated_with::enzyme encoded by the SIRT6 gene. SIRT6 functions in multiple molecular pathways related to aging, including is_associated_with::DNA repair, is_associated_with::telomere maintenance, is_associated_with::glycolysis and is_associated_with::inflammation.

Function
Studies in mice have revealed that Sirt6 is essential for post-natal development and survival. Sirt6 is_associated_with::knock-out mice, in which the gene encoding Sirt6 has been disrupted, exhibit a severe is_associated_with::progeria, or premature aging syndrome, characterized by spinal curvature, greying of the fur, is_associated_with::lymphopenia and low levels of blood glucose. The lifespan of Sirt6 knock-out mice is typically one to three months, dependent upon the strain in which the Sirt6 gene has been deleted. By contrast, wild type mice, which retain expression of Sirt6, exhibit a maximum lifespan of two to four years.

Mice which have been is_associated_with::genetically engineered to overexpress, or produce more, Sirt6 protein exhibit an extended maximum lifespan. This lifespan extension, of about 15-16 percent, is observed only in male mice.

Clinical relevance
The medical and therapeutic relevance of SIRT6 in humans remains unclear. SIRT6 may be an attractive drug target for pharmocological activation in several diseases. Because SIRT6 attenuates is_associated_with::glycolysis and inflammation, the gene is of medical interest in the context of several diseases, including is_associated_with::diabetes and is_associated_with::arthritis. Additionally, SIRT6 may be relevant in the context of is_associated_with::cancer. Several studies have indicated that SIRT6 is selectively inactivated during is_associated_with::oncogenesis in a variety of tumor types; a separate study demonstrated that SIRT6 overexpression was selectively cytotoxic to cancer cells.