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Sex difference in pathology of the ageing gut mediates the greater response of female lifespan to dietary restriction.

Regan, JC; Khericha, M; Dobson, AJ; Bolukbasi, E; Rattanavirotkul, N; Partridge, L; (2016) Sex difference in pathology of the ageing gut mediates the greater response of female lifespan to dietary restriction. eLife , 5 , Article e10956. 10.7554/eLife.10956. Green open access

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Abstract

Women live on average longer than men, but have greater levels of late-life morbidity. We have uncovered a substantial sex difference in the pathology of the ageing gut in Drosophila. The intestinal epithelium of the ageing female undergoes major deterioration, driven by intestinal stem cell (ISC) division, while lower ISC activity in males associates with delay or absence of pathology, and better barrier function, even at old ages. Males succumb to intestinal challenges to which females are resistant, associated with fewer proliferating ISCs, suggesting a trade-off between highly active repair mechanisms and late-life pathology in females. Dietary restriction reduces gut pathology in ageing females, and extends female lifespan more than male. By genetic sex reversal of a specific gut region, we induced female-like ageing pathologies in males, associated with decreased lifespan, but also with a greater increase in longevity in response to dietary restriction.

Type: Article
Title: Sex difference in pathology of the ageing gut mediates the greater response of female lifespan to dietary restriction.
Open access status: An open access version is available from UCL Discovery
DOI: 10.7554/eLife.10956
Publisher version: http://dx.doi.org/10.7554/eLife.10956
Language: English
Additional information: Copyright © Regan et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Keywords: D. melanogaster, developmental biology, immunology, stem cells
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/1476821
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