Abstract
Although the gonad primarily functions in procreation, it also affects animal life span. Here, we show that removal of the Caenorhabditis elegans germ line triggers a switch in the regulatory state of the organism to promote longevity, co-opting components involved in larval developmental timing circuits. These components include the DAF-12 steroid receptor, which is involved in the larval stage two-to-stage three (L2-L3) transition and up-regulates members of the let-7 microRNA (miRNA) family. The miRNAs target an early larval nuclear factor lin-14 and akt-1/kinase, thereby stimulating DAF-16/FOXO signaling to extend life. Our studies suggest that metazoan life span is coupled to the gonad through elements of a developmental timer.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Caenorhabditis elegans / genetics
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Caenorhabditis elegans / growth & development
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Caenorhabditis elegans / physiology*
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / physiology*
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Forkhead Transcription Factors
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Gene Expression Regulation, Developmental
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Germ Cells / metabolism
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Gonads / metabolism*
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Larva / genetics
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Larva / growth & development
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Larva / physiology
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Longevity / genetics
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Longevity / physiology*
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MicroRNAs / genetics
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MicroRNAs / metabolism*
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Nuclear Proteins / genetics
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Nuclear Proteins / physiology
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Proto-Oncogene Proteins c-akt / genetics
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Proto-Oncogene Proteins c-akt / physiology
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Receptors, Cytoplasmic and Nuclear / genetics
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Receptors, Cytoplasmic and Nuclear / physiology*
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Receptors, Steroid / genetics
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Receptors, Steroid / physiology*
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Signal Transduction
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Transcription Factors / genetics
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Transcription Factors / physiology
Substances
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Caenorhabditis elegans Proteins
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DAF-12 protein, C elegans
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Forkhead Transcription Factors
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LIN-14 protein, C elegans
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MicroRNAs
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Nuclear Proteins
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Receptors, Cytoplasmic and Nuclear
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Receptors, Steroid
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Transcription Factors
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daf-16 protein, C elegans
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Proto-Oncogene Proteins c-akt
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akt-1 protein, C elegans