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Polr3b heterozygosity in mice induces both beneficial and deleterious effects on health during ageing with no effect on lifespan

Borland, Gillian, Wilkie, Stephen, E., Thomson, Jackie, Wang, Zhe, Tullet, Jennifer M.A., Alic, Nazif, Selman, Colin (2024) Polr3b heterozygosity in mice induces both beneficial and deleterious effects on health during ageing with no effect on lifespan. Aging Cell, . Article Number e14141. ISSN 1474-9718. E-ISSN 1474-9726. (doi:10.1111/acel.14141) (KAR id:105281)


The genetic pathways that modulate ageing in multicellular organisms are typically highly conserved across wide evolutionary distances. Recently RNA polymerase III (Pol III) was shown to promote ageing in yeast, C. elegans and D. melanogaster. In this study we investigated the role of Pol III in mammalian ageing using C57BL/6N mice heterozygous for Pol III (Polr3b+/−). We identified sexually dimorphic, organ-specific beneficial as well as detrimental effects of the Polr3b+/− mutation on health. Female Polr3b+/− mice displayed improved bone health during ageing, but their ability to maintain an effective gut barrier function was compromised and they were susceptible to idiopathic dermatitis (ID). In contrast, male Polr3b+/− mice were lighter than wild-type (WT) males and had a significantly improved gut barrier function in old age. Several metabolic parameters were affected by both age and sex, but no genotype differences were detected. Neither male nor female Polr3b+/− mice were long-lived compared to WT controls. Overall, we find no evidence that a reduced Pol III activity extends mouse lifespan but we do find some potential organ- and sex-specific benefits for old-age health.

Item Type: Article
DOI/Identification number: 10.1111/acel.14141
Additional information: For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.
Uncontrolled keywords: Aging; C57BL/6N; healthspan; longevity; RNA polymerase III
Subjects: Q Science > QP Physiology (Living systems)
Divisions: Divisions > Division of Natural Sciences > Biosciences
Funders: Biotechnology and Biological Sciences Research Council (
Medical Research Council (
Depositing User: Jennifer Tullet
Date Deposited: 11 Mar 2024 13:49 UTC
Last Modified: 22 Mar 2024 14:21 UTC
Resource URI: (The current URI for this page, for reference purposes)

University of Kent Author Information

Tullet, Jennifer M.A..

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