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Free keywords:
Animals
Caenorhabditis elegans/genetics/growth & development/*physiology
Caenorhabditis elegans Proteins/genetics/*physiology
Forkhead Transcription Factors
Gene Expression Regulation, Developmental
Germ Cells/metabolism
Gonads/*metabolism
Larva/genetics/growth & development/physiology
Longevity/genetics/*physiology
MicroRNAs/genetics/*metabolism
Nuclear Proteins/genetics/physiology
Proto-Oncogene Proteins c-akt/genetics/physiology
Receptors, Cytoplasmic and Nuclear/genetics/*physiology
Receptors, Steroid/genetics/*physiology
Signal Transduction
Transcription Factors/genetics/physiology
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.