Final published version
Licence: CC BY: Creative Commons Attribution 4.0 International License
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - Partial Inhibition of RNA Polymerase I Promotes Animal Health and Longevity
AU - Martinez Corrales, Guillermo
AU - Filer, Danny
AU - Wenz, Katharina C.
AU - Rogan, Abbie
AU - Phillips, George
AU - Li, Mengjia
AU - Feseha, Yodit
AU - Broughton, Susan
AU - Alic, Nazif
PY - 2020/2/11
Y1 - 2020/2/11
N2 - 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.
AB - 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.
KW - RNA polymerase I
KW - aging
KW - ribosomal RNA/DNA
KW - Drosophila
KW - old-age health
KW - lifespan
KW - longevity
U2 - 10.1016/j.celrep.2020.01.017
DO - 10.1016/j.celrep.2020.01.017
M3 - Journal article
VL - 30
SP - 1661
EP - 1669
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 6
ER -