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Life‐span extension by dietary restriction is mediated by NLP‐7 signaling and coelomocyte endocytosis in C. elegans
Author(s) -
Park SangKyu,
Link Christopher D.,
Johnson Thomas E.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.09-142984
Subject(s) - endocytosis , longevity , mutant , gene , biology , gene knockdown , caenorhabditis elegans , genetics , rna interference , microbiology and biotechnology , receptor , rna
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 .—Park, S.‐K., Link, C. D., Johnson, T. E. Life‐span extension by dietary restriction is mediated by NLP‐7 signaling and coelomocyte endocytosis in C. elegans . FASEB J . 24, 383–392 (2010). www.fasebj.org