Sirt6 links genome stability and tumor suppression pathways to longevity maintenance

Thesis (Ph. D.)--University of Rochester. Department of Biology, 2016.Aging is a nearly universal feature of life. Yet despite the ubiquity of aging, the molecular mechanisms which drive aging and age-related disease remain far from wellunderstood. This project investigates the molecular etiology of aging using a reverse genetics approach. Namely, my research has focused on the longevity gene, SIRT6, with a particular emphasis on elucidating how the gene contributes to longevity assurance and tumor suppression pathways. Using a series of molecular, animal and bioinformatic experiments, I identify several novel pathways by which SIRT6 contributes to longevity maintenance, including suppression of retroelements, stimulation of DNA DSB repair and suppression of oncogenesis. Cumulatively, my research adds to the growing body of evidence which suggests that SIRT6 is an important regulator of lifespan in mammals. Further, I provide evidence that it is possible to modulate SIRT6 activity, and that doing so may be a viable strategy for ameliorating or delaying the onset of age-related pathologies