cep-1/p53-dependent dysplastic pathology of the aging C. elegans gonad.

Aging
Mathew D McGeeSimon Melov

Abstract

The C. elegans germline and somatic gonad are actively developing until the animal reaches adulthood, and then continue to undergo striking changes as the animal ages. Reported changes include a depletion of available sperm, a decrease in oocyte quality up till mid-life, a reduction in germline nuclei, a decrease in fertility, and an accumulation of DNA in the midbody of aging C. elegans. Here, we have focused on the aging gonad in old animals, and show in detail that the aging gonad undergoes a massive uterine growth composed of endoreduplicating oocytes, yolk, and expanses of chromatin. We use a novel series of imaging techniques in combination with histological methodology for reconstructing aged worms in 3-dimensions, and show in old animals growing masses swelling inside the uterus to occupy most of the diameter of the worm. We link this accelerated growth to the cep-1/p53 tumor suppressor. Because cep-1 is required for DNA damage induced apoptosis, and daf-2 limits longevity, these results suggest a role for age-related DNA damage in dysplastic uterine growths, which in some respects resemble premalignant changes that can occur in aging mammals.

References

Oct 29, 2003·BMC Biotechnology·Nathaniel J SzewczykCatharine A Conley
Feb 20, 2007·PLoS Genetics·Stacie E HughesKerry Kornfeld
Mar 24, 2007·Nature Reviews. Molecular Cell Biology·Karen H Vousden, David P Lane
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Dec 6, 2008·PLoS Genetics·Sara Andux, Ronald E Ellis

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Citations

Apr 1, 2015·Molecular & Cellular Oncology·Emmanouil KyriakakisNektarios Tavernarakis
Feb 28, 2014·Oncoimmunology·Mikhail V Blagosklonny
Nov 5, 2013·Cancer Biology & Therapy·Olga V LeontievaMikhail V Blagosklonny
Feb 9, 2019·Aging Cell·Heehwa G SonSeung-Jae V Lee
Oct 27, 2016·Oncotarget·Yila de la GuardiaDavid Gems
Nov 21, 2012·Cell Cycle·Ivano AmelioGerry Melino
May 10, 2016·F1000Research·Simon Melov
Jun 22, 2018·Npj Aging and Mechanisms of Disease·Hongyuan WangDavid Gems
Jun 2, 2021·Aging Cell·Hanna AchacheYonatan B Tzur

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Methods Mentioned

BETA
imaging techniques
PCR
light microscopy

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