Authors: Park SK; Link CD; Johnson TE
Abstract: Recent studies have shown that the rate of aging can be modulated by diverse interventions. Dietary restriction is the most widely used intervention to promote longevity; however, the mechanisms underlying the effect of dietary restriction remain elusive. In a previous study, we identified two novel genes, nlp-7 and cup-4, required for normal longevity in Caenorhabditis elegans. nlp-7 is one of a set of neuropeptide-like protein genes; cup-4 encodes an ion-channel involved in endocytosis by coelomocytes. Here, we assess whether nlp-7 and cup-4 mediate longevity increases by dietary restriction. RNAi of nlp-7 or cup-4 significantly reduces the life span of the eat-2 mutant, a genetic model of dietary restriction, but has no effect on the life span of long-lived mutants resulting from reduced insulin/IGF-1 signaling or dysfunction of the mitochondrial electron transport chain. The life-span extension observed in wild-type N2 worms by dietary restriction using bacterial dilution is prevented significantly in nlp-7 and cup-4 mutants. RNAi knockdown of genes encoding candidate receptors of NLP-7 and genes involved in endocytosis by coelomocytes also specifically shorten the life span of the eat-2 mutant. We conclude that two novel pathways, NLP-7 signaling and endocytosis by coelomocytes, are required for life extension under dietary restriction in C. elegans.Keywords: Aging/drug effects/physiology; Animals; Caenorhabditis elegans/cytology; Caenorhabditis elegans Proteins/*physiology; Caloric Restriction; Endocytosis/*physiology; Longevity/*genetics; Neuropeptides/*physiology; Oxidative Stress; RNA Interference; Signal Transduction/*physiology
Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Date: Sept. 29, 2009
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Park SK, Link CD, Johnson TE (2010) Life-span extension by dietary restriction is mediated by NLP-7 signaling and coelomocyte endocytosis in C. elegans. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 24: 383-92.