Loss of intestinal nuclei and intestinal integrity in aging C. elegans.
Aging Cell. 2011 Aug; 10(4):699-710
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While there are many studies of genes and other factors affecting Caenorhabditis elegans lifespan, very little is known about the pathology of ageing in this species. This microscopic study provides useful baseline information about age changes in C. elegans anatomy.
The short-lived, free-living nematode worm C. elegans has long been used as a model organism to study mechanisms of ageing, but the nature of such mechanisms still remain elusive. Many interventions (particularly involving gene manipulation) can slow C. elegans ageing, but the mechanisms involved remain unclear. Here, it would be very helpful to know what exactly it is that kills ageing C. elegans, since extension of lifespan must, to some extent, work through prevention of age-related pathology. Yet, there is a paucity of information on this topic. This is the second excellent study from the Melov lab aiming to provide baseline information on age changes in C. elegans cytology and anatomy (the first is {1}). This study includes 3D reconstructions of stained, serial sectioned tissues, which can be viewed as animated tours through the anatomy of young versus old worms. Particularly striking are the effects of ageing on the morphology of intestinal cells, including loss of microvilli, and strikingly high levels of yolk accumulation in the body cavity (confirming earlier observations).
Gems D: F1000Prime Recommendation of [McGee MD et al., Aging Cell 2011, 10(4):699-710]. In F1000Prime, 12 Sep 2011; DOI: 10.3410/f.13200085.14542277. F1000Prime.com/13200085#eval14542277
F1000Prime Recommendations, Dissents and Comments for [McGee MD et al., Aging Cell 2011, 10(4):699-710]. In F1000Prime, 20 Jun 2013; F1000Prime.com/13200085
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The roundworm C. elegans is widely used as an aging model, with hundreds of genes identified that modulate aging (Kaeberlein et al., 2002. Mech. Ageing Dev.123, 1115-1119). 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. Dev. Biol.56, 110-156; Sulston et al., 1983. Dev. Biol.100, 64-119.). 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. Nature419, 808-814), neurons (Herndon et al., 2002), intestine and yolk granules (Garigan et al., 2002. Genetics161, 1101-1112; Herndon et al., 2002), nuclear architecture (Haithcock et al., 2005. Proc. Natl Acad. Sci. USA102, 16690-16695), tail nuclei (Golden et al., 2007. Aging Cell6, 179-188), 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 3D volumetric reconstructions and characterized age-related morphological changes in multiple wild-type individuals at different ages. This enabled us to identify several novel pathologies with age in the C. elegans intestine, including the loss of critical nuclei, the degradation of intestinal microvilli, changes in the size, shape, and cytoplasmic contents of the intestine, and altered morphologies caused by 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 multicellular organism.
© 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.
DOI: 10.1111/j.1474-9726.2011.00713.x
PMID: 21501374
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