STKE: Live Larger, Live Longer

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Science  28 Feb 2003:
Vol. 299, Issue 5611, pp. 1285c
DOI: 10.1126/science.299.5611.1285c

Control of metabolism and body size are key molecular mechanisms involved in controlling life-span. Hirose et al. screened for mutants in Caenorhabditis elegans that were larger than normal. Several mutations occurred in the gene egl-4, which encodes a guanosine 3',5'-monophosphate (cGMP)-dependent protein kinase. Phenotypically the worms were 50 to 100% larger, lived 50% longer, and had delayed egg laying and decreased brood size compared to wild-type worms. The larger size was due to increased cell volume, not cell number. Mutations in the genes of the insulin signaling pathway also increase life-span, and when the gene daf-16, which encodes a putative transcription factor, was also knocked out, life-span extension was eliminated. Double knockout of egl-4 and sma-6 or dbl-1, which encode components of the transforming growth factor pathway, suppressed the size phenotype of egl-4. Thus, a cGMP-dependent protein kinase appears to be part of the network of signaling processes regulating cell size and organism longevity. — NG

Development 130, 1089 (2003).

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