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Goudeau J  Aguilaniu H 《Aging cell》2010,9(6):991-1003
Oxidatively damaged proteins accumulate with age in many species (Stadtman (1992) Science 257 , 1220–1224). This means that damage must be reset at the time of reproduction. To visualize this resetting in the roundworm Caenorhabditis elegans, a novel immunofluorescence technique that allows the detection of carbonylated proteins in situ was developed. The application of this technique revealed that carbonylated proteins are eliminated during C. elegans reproduction. This purging occurs abruptly within the germline at the time of oocyte maturation. Surprisingly, the germline was markedly more oxidized than the surrounding somatic tissues. Because distinct mechanisms have been proposed to explain damage elimination in yeast and mice (Aguilaniu et al. (2003) Science 299 , 1751–1753; Hernebring et al. (2006) Proc Natl Acad Sci USA 103 , 7700–7705), possible common mechanisms between worms and one of these systems were tested. The results show that, unlike in yeast (Aguilaniu et al. (2003) Science 299 , 1751–1753; Erjavec et al. (2008) Proc Natl Acad Sci USA 105 , 18764–18769), the elimination of carbonylated proteins in worms does not require the presence of the longevity‐ensuring gene, SIR‐2.1. However, similar to findings in mice (Hernebring et al. (2006) Proc Natl Acad Sci USA 103 , 7700–7705), proteasome activity in the germline is required for the resetting of carbonylated proteins during reproduction in C. elegans. Thus, oxidatively damaged proteins are eliminated during reproduction in worms through the proteasome. This finding suggests that the resetting of damaged proteins during reproduction is conserved, therefore validating the use of C. elegans as a model to study the molecular basis of damage elimination.  相似文献   

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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 . Nature 419 , 808–814), neurons ( Herndon et al., 2002 ), intestine and yolk granules ( Garigan et al., 2002 . Genetics 161 , 1101–1112; Herndon et al., 2002 ), nuclear architecture ( Haithcock et al., 2005 . Proc. Natl Acad. Sci. USA 102 , 16690–16695), tail nuclei ( Golden et al., 2007 . Aging Cell 6 , 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.  相似文献   

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Pheromone responses are highly context dependent. For example, the C.?elegans pheromone ascaroside C9 (ascr#3) is repulsive to wild-type hermaphrodites, attractive to wild-type males, and usually neutral to "social" hermaphrodites with reduced activity of the npr-1 neuropeptide receptor gene. We show here that these distinct behavioral responses arise from overlapping push-pull circuits driven by two classes of pheromone-sensing neurons. The ADL sensory neurons detect C9 and, in?wild-type hermaphrodites, drive C9 repulsion through their chemical synapses. In npr-1 mutant hermaphrodites, C9 repulsion is reduced by the recruitment of a gap junction circuit that antagonizes ADL chemical synapses. In males, ADL sensory responses are diminished; in addition, a second pheromone-sensing neuron, ASK, antagonizes C9 repulsion. The additive effects of these antagonistic circuit elements generate attractive, repulsive, or neutral pheromone responses. Neuronal modulation by circuit state and sex, and flexibility in synaptic output pathways, may permit small circuits to maximize their adaptive behavioral outputs.  相似文献   

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