Editors' ChoiceLONGEVITY

Diet of Worms

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Science's STKE  05 Jun 2007:
Vol. 2007, Issue 389, pp. tw196
DOI: 10.1126/stke.3892007tw196

In many organisms, dietary restriction leads to an increased life span and a delay in various conditions associated with aging. Panowski et al. found that, unlike wild-type worms, Caenorhabditis elegans in which the pha-4 gene was inactivated failed to live longer under conditions in which the concentration of bacteria they were fed was limited. The effect on life span of pha-4, which encodes a transcription factor implicated in foregut development that has a sequence similar to that of the mammalian Foxa transcription factors, was specifically related to dietary restriction. Loss of pha-4 had no effect on longevity associated with decreased insulin and insulin-like growth factor signaling, nor did it affect longevity associated with decreased activity of the mitochondrial electron transport chain. Moreover, the effect of pha-4 on longevity was independent of its role in foregut development. Real-time polymerase chain reaction studies determined that the abundance of PHA-4 mRNA was increased in response to dietary restriction. The authors created 11 individual C. elegans lines with increased abundance of PHA-4 and found a statistically significant increase in the longevity of nine of these lines. A restrictive diet resulted in the increased abundance of several mitochondrial superoxide dismutases, enzymes important in protecting cells from the oxidative damage that can cause aging. Expression of the genes for these enzymes was decreased in the absence of pha-4. In another study, Bishop and Guarente found that mutant C. elegans lacking another transcription factor, SKN-1, had a decreased life span. SKN-1 is important in development, particularly in the intestine. The authors found that, similar to PHA-4, lack of SKN-1 prevented dietary-restriction-induced longevity. Lack of SKN-1 also had no effect on longevity associated with decreased insulin and insulin-like growth factor signaling. As well as being present in the intestine, SKN-1 is found in two sensory neurons (known as ASI neurons) in the head of C. elegans, and the authors found that it was this neuronal-associated SKN-1 that was responsible for mediating longevity. The abundance of SKN-1 in the ASI neurons was increased in C. elegans that had a restricted diet, compared with that in nonrestricted worms. The authors proposed that the increased abundance of SKN-1 causes the ASI neurons to release a hormonal signal that increases the rate of respiration of cells in the peripheral tissues, leading to longevity. The implications of these two studies are discussed by Antebi.

S. H. Panowski, S. Wolff, H. Aguilaniu, J. Durieux, A. Dillin, PHA-4/Foxa mediates diet-restriction-induced longevity of C. elegans. Nature 447, 550-555 (2007). [PubMed]

N. A. Bishop, L. Guarente, Two neurons mediate diet-restriction-induced longevity in C. elegans. Nature 447, 545-549 (2007). [PubMed]

A. Antebi, When less is more. Nature 447, 536-537 (2007). [PubMed]

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