Editors' ChoiceSize Control

Live Larger, Live Longer

Science's STKE  11 Feb 2003:
Vol. 2003, Issue 169, pp. tw58-TW58
DOI: 10.1126/stke.2003.169.tw58

Control of metabolism and body size has been often named as molecular mechanisms contributing to longevity. Hirose et al. developed an automated screen for mutants in Caenorhabditis elegans that were larger than normal. Several of 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 with wild-type worms. The larger size was due to increased cell volume, not cell number. Interactions with other genes implicated in life-span and body size control were investigated, for example, genes of the insulin signaling pathway or transforming growth factor β pathway. Mutations in the genes of the insulin signaling pathway also extend the life-span, unless the gene daf-16, which encodes a putative transcription factor, is also knocked out. Double-knockout of egl-4 and daf-16 resulted in worms with the same life-span as wild-type worms, which shows that Egl-4 is also in the pathways that converge on Daf-16. Double-knockout of egl-4 and sma-6 or dbl-1, which encode components of the transforming growth factor β pathway, suppressed the size phenotype of egl-4 mutants. Thus, a cGMP-dependent protein kinase appears to be part of the network of signaling processes regulating cell size and organismal longevity.

T. Hirose, Y. Nakano, Y. Nagamatsu, T. Misumi, H. Ohta, Y. Ohshima, Cyclic GMP-dependent protein kinase EGL-4 controls body size and lifespan in C. elegans. Development 130, 1089-1099 (2003). [Abstract] [Full Text]