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

Aging (Albany NY). 2012 Apr;4(4):256-69. doi: 10.18632/aging.100448.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics*
  • Animals
  • Apoptosis
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / metabolism*
  • DNA Damage
  • Germ Cells / metabolism*
  • Gonads / metabolism
  • Gonads / pathology*
  • Humans
  • Imaging, Three-Dimensional / methods
  • Receptor, Insulin / metabolism*
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • CEP-1 protein, C elegans
  • Caenorhabditis elegans Proteins
  • Tumor Suppressor Protein p53
  • DAF-2 protein, C elegans
  • Receptor, Insulin