1. Developmental Biology
  2. Immunology and Inflammation
Download icon

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

Short Report
  • Cited 99
  • Views 6,850
  • Annotations
Cite this article as: eLife 2016;5:e10956 doi: 10.7554/eLife.10956

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.

Article and author information

Author details

  1. Jennifer C Regan

    Institute of Healthy Ageing, Department of Genetics, Evolution, and Environment, University College London, London, United Kingdom
    For correspondence
    j.regan@ucl.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
  2. Mobina Khericha

    Institute of Healthy Ageing, Department of Genetics, Evolution, and Environment, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Adam J Dobson

    Institute of Healthy Ageing, Department of Genetics, Evolution, and Environment, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Ekin Bolukbasi

    Institute of Healthy Ageing, Department of Genetics, Evolution, and Environment, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Nattaphong Rattanavirotkul

    Institute of Healthy Ageing, Department of Genetics, Evolution, and Environment, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Linda Partridge

    Institute of Healthy Ageing, Department of Genetics, Evolution, and Environment, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Andrew Dillin, Howard Hughes Medical Institute, University of California, Berkeley, United States

Publication history

  1. Received: August 18, 2015
  2. Accepted: February 2, 2016
  3. Accepted Manuscript published: February 16, 2016 (version 1)
  4. Version of Record published: March 14, 2016 (version 2)

Copyright

© 2016, Regan et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 6,850
    Page views
  • 1,514
    Downloads
  • 99
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Developmental Biology
    2. Neuroscience
    Baruch Haimson et al.
    Research Article Updated

    Peripheral and intraspinal feedback is required to shape and update the output of spinal networks that execute motor behavior. We report that lumbar dI2 spinal interneurons in chicks receive synaptic input from afferents and premotor neurons. These interneurons innervate contralateral premotor networks in the lumbar and brachial spinal cord, and their ascending projections innervate the cerebellum. These findings suggest that dI2 neurons function as interneurons in local lumbar circuits, are involved in lumbo-brachial coupling, and that part of them deliver peripheral and intraspinal feedback to the cerebellum. Silencing of dI2 neurons leads to destabilized stepping in posthatching day 8 hatchlings, with occasional collapses, variable step profiles, and a wide-base walking gait, suggesting that dI2 neurons may contribute to the stabilization of the bipedal gait.

    1. Developmental Biology
    2. Evolutionary Biology
    Tom Dierschke et al.
    Research Article

    Eukaryotic life cycles alternate between haploid and diploid phases and in phylogenetically diverse unicellular eukaryotes, expression of paralogous homeodomain genes in gametes primes the haploid-to-diploid transition. In the unicellular Chlorophyte alga Chlamydomonas KNOX and BELL TALE-homeodomain genes mediate this transition. We demonstrate that in the liverwort Marchantia polymorpha paternal (sperm) expression of three of five phylogenetically diverse BELL genes, MpBELL234, and maternal (egg) expression of both MpKNOX1 and MpBELL34 mediate the haploid-to-diploid transition. Loss-of-function alleles of MpKNOX1 result in zygotic arrest, whereas loss of either maternal or paternal MpBELL234 results in variable zygotic and early embryonic arrest. Expression of MpKNOX1 and MpBELL34 during diploid sporophyte development is consistent with a later role for these genes in patterning the sporophyte. These results indicate that the ancestral mechanism to activate diploid gene expression was retained in early diverging land plants and subsequently co-opted during evolution of the diploid sporophyte body.