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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 MA; 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 e14141. 10.1111/acel.14141. (In press). Green open access

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Abstract

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.

Type: Article
Title: Polr3b heterozygosity in mice induces both beneficial and deleterious effects on health during ageing with no effect on lifespan
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/acel.14141
Publisher version: http://dx.doi.org/10.1111/acel.14141
Language: English
Additional information: © 2024 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: Science & Technology, Life Sciences & Biomedicine, Cell Biology, Geriatrics & Gerontology, Aging, C57BL/6N, healthspan, longevity, RNA polymerase III, MODEL ORGANISMS, LONGEVITY
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
URI: https://discovery.ucl.ac.uk/id/eprint/10191274
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