Loss of intestinal nuclei and intestinal integrity in aging C. elegans

Abstract

Summary The roundworm C. elegans is widely used as an aging model, with hundreds of genes identified that modulate aging(Kaeberlein et al. 2002). The development and bodyplan of the 959 cells comprising the adult have been well described and established for more than 25 years(Sulston & Horvitz 1977; Sulston et al. 1983). However, morphological changes with age in this optically transparent animal are less well understood, with only a handful of studies investigating the pathobiology of aging. Age related changes in muscle(Herndon et al. 2002), neurons(Herndon et al. 2002), intestine and yolk granules(Garigan et al. 2002; Herndon et al. 2002), nuclear architecture(Haithcock et al. 2005), tail nuclei(Golden et al. 2007), and the germline(Golden et al. 2007) have been observed via a variety of traditional relatively low-throughput methods. We report here a number of novel approaches to study the pathobiology of aging C. elegans. We combined histological staining of serial-sectioned tissues, transmission electron microscopy, and confocal microscopy with 3-D volumetric reconstructions, and characterized age-related morphological changes of multiple wild-type individuals at different ages. This enabled us to identify several novel pathologies with age in the C. elegans intestine, including loss of critical nuclei, degradation of intestinal microvilli, changes in the size, shape, and cytoplasmic contents of the intestine, and altered morphologies due to ingested bacteria. The three-dimensional models we have created of tissues and cellular components from multiple individuals of different ages, represent a unique resource to demonstrate global heterogeneity of a multi-cellular organism.

Alternative Perspectives on Aging inCaenorhabditis elegans: Reactive Oxygen Species or Hyperfunction?

“…In elderly worms, the lumen of the entire alimentary canal (pharynx and intestine) can become clogged up (constipated) with packed E. coli (15). Aging intestinal cells also show marked deterioration, including atrophy, abnormalities in nuclear morphology (e.g., affecting the nuclear lamina), and loss of nuclei and microvilli (15,18,21,24,37). Although constipation is a problem of E. coli hyperproliferation, there is no obvious evidence that hyperfunction within intestinal cells causes their degeneration.…”

“…In each part, young adult worm is shown above and an older worm below. Redrawn after published observations (12,15,18,24,27,37,48).…”

“…In worms with sperm, VIT-2::GFP is seen only in the intestine and oocytes. When sperm depletes, yolk rapidly appears throughout the worm, particularly in the body cavity, where it accumulates to high levels (12,15,24,37) (Fig. 3).…”

Autophagy and genomic integrity

“…62 Similarly, removal of nuclei from intestinal epithelial cells of Caernohabiditis elegans also occurs through autophagy. 63 Autophagy of nuclear components in eukaryotes, or piecemeal microautophagy of the nucleus (PMN), was initially described in Saccharomyces cerevisae. It is triggered by nutrient deprivation and occurs through the release of nuclear portions into the vacuole, 64 followed by digestion by hydrolases.…”

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“…subtilis fed worms live substantially longer than worms grown on E. coli [6] and these diets appear to induce different causes of death to the worms [8,49]. It has been recently proposed that the C. elegans life span difference observed when the worm diet is changed from the standard E. coli to B. subtilis is mainly due to the persistent antioxidant effect of CoQ present in the E. coli diet, which leads to an imbalance in cellular REDOX homeostasis [11].…”