Speaker: Jackson Taylor, Cleveland State University assistant professor in the Center for Gene Regulation in Health and Disease

Title: "Role of Sirt6 in lifespan regulation and tauopathy"

Abstract: Sirt6 is a multifunctional enzyme that regulates diverse cellular processes such as metabolism, DNA repair, and aging. Sirt6 overexpression (OE) extends lifespan and healthspan in mice, but the underlying cellular mechanisms are unclear. This talk will focus on our research to determine mechanisms by which Sirt6 regulates aging and disease, using Drosophila melanogaster (fruit flies) as a model system. We recently reported that Sirt6 overexpression (OE) in flies produces robust lifespan extension in both sexes. Sirt6 OE flies have reduced protein translation rates, a phenotype associated with longevity. Mechanistically, Sirt6 OE appears to reduce translation by transcriptionally repressing ribosome biogenesis genes, many of which are also Myc target genes. Sirt6 OE blocks multiple effects of Myc overexpression, including increased translation rates and increased expression of ribosome biogenesis genes. Myc haploinsufficiency, which normally extends lifespan, does not convey additional lifespan extension to Sirt6 OE flies. Together, these data suggest Sirt6 OE extends lifespan in part by inhibiting Myc activity, leading to decreased ribosome biogenesis gene expression and translation rates. Our preliminary data also indicate that Sirt6 acts as a positive regulator of proteostasis, which declines with age and is thought to be a key driver of the aging process and age-related neurodegenerative disease. Lastly, I will discuss our recent findings that Sirt6 OE is protective against neurodegenerative phenotypes in fly models of human tauopathy – a class of diseases which includes Alzheimer's Disease and is characterized by inclusions of tau protein.

Host: Ping Kang, adjunct assistant professor in genetics, development and cell biology