Martínez Corrales, G;
Filer, D;
Wenz, K;
Abbie, R;
George, P;
Li, M;
Feseha, Y;
... Alic, N; + view all
(2020)
Partial inhibition of RNA polymerase I promotes animal health and longevity.
Cell Reports
, 30
(6)
1661-16669.e4.
10.1016/j.celrep.2020.01.017.
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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, 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.
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