The Histone Deacetylase SIRT6 Modulates Genomic Stability, Neurodegeneration and aging

Even though multiple studies have linked aging to chronic accumulation of DNA damage, the molecular mechanisms behind this phenomenon have not been determined. A class of proteins called sirtuin (SIR) is known to influence a wide range of cellular processes. One sirtuin, SIRT6, is an enzyme involved in DNA repair and metabolism. SIRT6-deficient mice die of an inadequate supply of glucose to their brains at 4 weeks of age. These mice show signs of premature aging and instability in the processing of genetic information. Conversely, mice with high SIRT6 activity live longer than normal lives. SIRT6 is the first mammalian sirtuin to be linked to increased life expectancy. Dr. Toiber will investigate whether low levels of SIRT6 in the brain can lead to premature neurodegeneration. She will document the effects of SIRT6 impairment at behavioral and molecular levels. Her goal is to learn what modulates how brain cells respond to DNA damage and what causes the damage response to become less efficient in old age.