Research Papers: Gerotarget (Focus on Aging):

Run-on of germline apoptosis promotes gonad senescence in C. elegans

Yila de la Guardia, Ann F. Gilliat, Josephine Hellberg, Peter Rennert, Filipe Cabreiro and David Gems _

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Oncotarget. 2016; 7:39082-39096. https://doi.org/10.18632/oncotarget.9681

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Yila de la Guardia1, Ann F. Gilliat1, Josephine Hellberg1, Peter Rennert1, Filipe Cabreiro2 and David Gems1

1 Institute of Healthy Ageing, and Department of Genetics, Evolution and Environment, University College London, London, UK

2 Department of Structural and Molecular Biology, University College London, London, UK

Correspondence to:

David Gems, email:

Keywords: apoptosis, C. elegans, hyperfunction, pathology, senescence, Gerotarget

Received: April 12, 2016 Accepted: May 14, 2016 Published: May 31, 2016


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.

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