Partial Inhibition of RNA Polymerase I Promotes Animal Health and Longevity
Guillermo Martínez Corrales,
Danny Filer,
Katharina C. Wenz,
Abbie Rogan,
George Phillips,
Mengjia Li,
Yodit Feseha,
Susan J. Broughton,
Nazif Alic
Affiliations
Guillermo Martínez Corrales
Institute of Healthy Ageing and the Research Department of Genetics, Evolution, and Environment, University College London, WC1E 6BT London, UK
Danny Filer
Institute of Healthy Ageing and the Research Department of Genetics, Evolution, and Environment, University College London, WC1E 6BT London, UK
Katharina C. Wenz
Institute of Healthy Ageing and the Research Department of Genetics, Evolution, and Environment, University College London, WC1E 6BT London, UK
Abbie Rogan
Institute of Healthy Ageing and the Research Department of Genetics, Evolution, and Environment, University College London, WC1E 6BT London, UK
George Phillips
Institute of Healthy Ageing and the Research Department of Genetics, Evolution, and Environment, University College London, WC1E 6BT London, UK
Mengjia Li
Institute of Healthy Ageing and the Research Department of Genetics, Evolution, and Environment, University College London, WC1E 6BT London, UK
Yodit Feseha
Institute of Healthy Ageing and the Research Department of Genetics, Evolution, and Environment, University College London, WC1E 6BT London, UK
Susan J. Broughton
Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, LA1 4YQ Lancaster, UK
Nazif Alic
Institute of Healthy Ageing and the Research Department of Genetics, Evolution, and Environment, University College London, WC1E 6BT London, UK; Corresponding author
Summary: 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. : 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. Keywords: RNA polymerase I, aging, ribosomal RNA/DNA, Drosophila, old-age health, lifespan, longevity
