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

Regan, J. C., Khericha, M., Dobson, A. J. , Bolukbasi, E., Rattanavirotkul, N. and Partridge, L. (2016) Sex difference in pathology of the ageing gut mediates the greater response of female lifespan to dietary restriction. eLife, 5, e10956. (doi:10.7554/eLife.10956) (PMID:26878754) (PMCID:PMC4805549)

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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 aging gut in Drosophila. The intestinal epithelium of the aging 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 aging females, and extends female lifespan more than male. By genetic sex reversal of a specific gut region, we induced female-like aging pathologies in males, associated with decreased lifespan, but also with a greater increase in longevity in response to dietary restriction.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Dobson, Dr Adam
Authors: Regan, J. C., Khericha, M., Dobson, A. J., Bolukbasi, E., Rattanavirotkul, N., and Partridge, L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:eLife
Publisher:eLife Sciences Publications
ISSN:2050-084X
ISSN (Online):2050-084X
Copyright Holders:Copyright © 2016 Regan et al.
First Published:First published in eLife 5: e10956
Publisher Policy:Reproduced under a Creative Commons License

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