Partial Inhibition of RNA Polymerase I Promotes Animal Health and Longevity

• Published in: Cell reports (Cambridge) Vol. 30; no. 6; pp. 1661 - 1669.e4
• Main Authors: Martínez Corrales, Guillermo, Filer, Danny, Wenz, Katharina C., Rogan, Abbie, Phillips, George, Li, Mengjia, Feseha, Yodit, Broughton, Susan J., Alic, Nazif
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 11.02.2020; Cell Press; Elsevier
• Subjects: aging; Animals; Drosophila; Drosophila melanogaster - genetics; Drosophila Proteins - genetics; lifespan; Longevity; old-age health; ribosomal RNA/DNA; RNA polymerase I; RNA Polymerase I - antagonists & inhibitors; ribosomal RNA/DNA; Drosophila; lifespan; longevity; aging; old-age health; RNA polymerase I
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2020.01.017

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, age-related 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. [Display omitted] •Partial inhibition of RNA polymerase I (Pol I) can extend lifespan in the fruit fly•Reducing Pol I activity after development and only in the gut is sufficient•Pol I activity affects aging from both post-mitotic and mitotically active cells•Pol I activity affects the age-related decline in performance of multiple organs RNA polymerase I is a conserved eukaryotic enzyme that transcribes a single gene to generate precursor ribosomal RNA. Martínez Corrales et al. show that reducing the activity of this polymerase, even only in subsets of adult cells, can promote broad health benefits and longevity in the animal model Drosophila melanogaster.