de la Guardia, Y;
Gilliat, AF;
Hellberg, J;
Rennert, P;
Cabreiro, F;
Gems, D;
(2016)
Run-on of germline apoptosis promotes gonad senescence in C. elegans.
ONCOTARGET
, 7
(26)
pp. 39082-39096.
10.18632/oncotarget.9681.
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Abstract
Aging (senescence) includes causal mechanisms (etiologies) of late-life disease, which remain poorly understood. According to the recently proposed hyperfunction theory, based on the older theory of antagonistic pleiotropy, senescent pathologies can arise from futile, post-reproductive run-on of processes that in early life promote fitness. Here we apply this idea to investigate the etiology of senescent pathologies in the reproductive system of Caenorhabditis elegans hermaphrodites, particularly distal gonad degeneration and disintegration. Hermaphrodite germ cells frequently undergo “physiological” (non-damage-induced) apoptosis (PA) to provision growing oocytes. Run-on of such PA is a potential cause of age-related gonad degeneration. We document the continuation of germline apoptosis in later life, and report that genetically blocking or increasing PA retards or accelerates degeneration, respectively. In wild-type males, which lack germ line apoptosis, gonad disintegration does not occur. However, mutational induction of PA in males does not lead to gonad disintegration. These results suggest that as germ-cell proliferation rate declines markedly in aging hermaphrodites (but not males), run-on of PA becomes a pathogenic mechanism that promotes gonad degeneration. This illustrates how hyperfunction, or non-adaptive run-on in later life of a process that promotes fitness in early life, can promote atrophic senescent pathology in C. elegans.
Type: | Article |
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Title: | Run-on of germline apoptosis promotes gonad senescence in C. elegans |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.18632/oncotarget.9681 |
Publisher version: | http://dx.doi.org/10.18632/oncotarget.9681 |
Language: | English |
Additional information: | Creative Commons License. All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License. Copyright @ 2016 Impact Journals, LLC |
Keywords: | Science & Technology, Life Sciences & Biomedicine, Oncology, Cell Biology, apoptosis, C. elegans, hyperfunction, pathology, senescence, Gerotarget, NEMATODE CAENORHABDITIS-ELEGANS, OXIDATIVE DAMAGE THEORY, PROGRAMMED CELL-DEATH, LIFE-SPAN, OOCYTE DEVELOPMENT, TUMOR-SUPPRESSOR, LONGEVITY, STRESS, GROWTH, PROLIFERATION |
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/1516207 |
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