Partial Inhibition of RNA Polymerase I Promotes Animal Health and Longevity

Martinez Corrales, Guillermo and Filer, Danny and Wenz, Katharina C. and Rogan, Abbie and Phillips, George and Li, Mengjia and Feseha, Yodit and Broughton, Susan and Alic, Nazif (2020) Partial Inhibition of RNA Polymerase I Promotes Animal Health and Longevity. Cell Reports, 30 (6). pp. 1661-1669. ISSN 2211-1247

Abstract

Health and survival in old age can be improved by changes in gene expression. RNA polymerase (Pol) I is the essential, conserved enzyme whose task is to generate the pre-ribosomal RNA (rRNA). We find that reducing the levels of Pol I activity is sufficient to extend lifespan in the fruit fly. This effect can be recapitulated by partial, adult-restricted inhibition, with both enterocytes and stem cells of the adult midgut emerging as important cell types. In stem cells, Pol I appears to act in the same longevity pathway as Pol III, implicating rRNA synthesis in these cells as the key lifespan determinant. Importantly, reduction in Pol I activity delays broad, agerelated impairment and pathology, improving the function of diverse organ systems. Hence, our study shows that Pol I activity in the adult drives systemic, age-related decline in animal health and anticipates mortality.