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Author(s): Coleen T. Murphy [1]; Steven A. McCarroll [2]; Cornelia I. Bargmann [2]; Andrew Fraser [3]; Ravi S. Kamath [3]; Julie Ahringer [3]; Hao Li [1]; Cynthia Kenyon (corresponding author) [...]

Author(s): Kaveh Ashrafi [1, 2]; Francesca Y. Chang [1]; Jennifer L. Watts [3]; Andrew G. Fraser [4]; Ravi S. Kamath [4]; Julie Ahringer [4]; Gary Ruvkun (corresponding author) [1, 2] [...]

Author(s): Ravi S. Kamath [1, 2]; Andrew G. Fraser [1, 2, 4]; Yan Dong [1]; Gino Poulin [1]; Richard Durbin [3]; Monica Gotta [1, 4]; Alexander Kanapin [5]; Nathalie Le [...]

The genetic analysis of life span has revealed many interesting genes and pathways; however, our understanding of aging has been limited by the lack of a way to assay the aging process itself. Here we show that the tissues of aging worms have a characteristic appearance that is easy to recognize and quantify using Nomarski optics. We have used this assay to determine whether life-span mutations affect the rate of aging, to identify animals that age more rapidly than normal, and to infer the cause of death in C. elegans. Mutations that reduce insulin/IGF-1 signaling double the life span of C. elegans, and we find that tissue decline is slowed in these mutants. Thus this endocrine system appears to influence the rate at which tissues age. This effect extends even to the germline, which is the only mitotically active tissue in the adult. We find that Nomarski microscopy also allows a ready distinction between short-lived mutants that age more rapidly than normal and those that are simply sick, and we have identified an RNAi clone that confers a dramatic rapid-aging phenotype. This clone encodes the C. elegans heat-shock factor (HSF), a transcription factor that regulates the response to heat and oxidative stress. This suggests that heat-shock proteins, many of which act as chaperones, may function in normal animals to slow the rate. of aging. Finally, we have identified a cause of death of C. elegans: namely, proliferating bacteria. This suggests that increased susceptibility to bacterial infections contributes to mortality in these animals, just as it does in humans.

Author(s): Andrew G. Fraser [1, 2]; Ravi S. Kamath [1, 2]; Peder Zipperlen [1, 2]; Maruxa Martinez-Campos [1]; Marc Sohrmann [3]; Julie Ahringer (corresponding author) [1] Complete genomic sequence is [...]

Research has been conducted on genome stability in Caenorhabditis elegans somatic cells. The authors report the use of RNA interference-based ganome-wide screen in order to detect genes contributing to genome stability in C. elegans.

Caenorhabditis elegans homologues of the retinoblastoma (Rb) tumour suppressor complex specify cell lineage during development. Here we show that mutations in Rb pathway components enhance RNA interference (RNAi) and cause somatic cells to express genes and elaborate perinuclear structures normally limited to germline-specific P granules. Furthermore, particular gene inactivations that disrupt RNAi reverse the cell lineage transformations of Rb pathway mutants. These findings suggest that mutations in Rb pathway components cause cells to revert to patterns of gene expression normally restricted to germ cells. Rb may act by a similar mechanism to transform mammalian cells. [ABSTRACT FROM AUTHOR]

We report a systematic RNA interference (RNAi) screen of 5,690 Caenorhabditis elegans genes for gene inactivations that increase lifespan. We found that genes important for mitochondrial function stand out as a principal group of genes affecting C. elegans lifespan. A classical genetic screen identified a mutation in the mitochondrial leucyl-tRNA synthetase gene (lrs-2) that impaired mitochondrial function and was associated with longer-lifespan. The long-lived worms with impaired mitochondria had lower ATP content and oxygen consumption, but differential responses to free-radical and other stresses. These data suggest that the longer lifespan of C. elegans with compromised mitochrondria cannot simply be assigned to lower free radical production and suggest a more complex coupling of metabolism and longevity. [ABSTRACT FROM AUTHOR]