Dataset Information

The C. elegans microRNA mir-71 acts in neurons to promote germline-mediated longevity through regulation of DAF-16/FOXO.

ABSTRACT: The life span of Caenorhabditis elegans is controlled by signaling between the germline and the soma. Germ cell removal extends life span by triggering the activation of the DAF-16/FOXO transcription factor in the intestine. Here we analyze microRNA function in C. elegans aging and show that the microRNA mir-71 functions to mediate the effects of germ cell loss on life span. mir-71 is required for the life span extension caused by germline removal, and overexpression of mir-71 further extends the life span of animals lacking germ cells. mir-71 functions in the nervous system to facilitate the localization and transcriptional activity of DAF-16 in the intestine. Our findings reveal a microRNA-dependent mechanism of life span regulation by the germline and indicate that signaling among the gonad, the nervous system, and the intestine coordinates the life span of the entire organism.

SUBMITTER: Boulias K

PROVIDER: S-EPMC3344382 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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The C. elegans microRNA mir-71 acts in neurons to promote germline-mediated longevity through regulation of DAF-16/FOXO.

Boulias Konstantinos K Horvitz H Robert HR

Cell metabolism 20120401 4

The life span of Caenorhabditis elegans is controlled by signaling between the germline and the soma. Germ cell removal extends life span by triggering the activation of the DAF-16/FOXO transcription factor in the intestine. Here we analyze microRNA function in C. elegans aging and show that the microRNA mir-71 functions to mediate the effects of germ cell loss on life span. mir-71 is required for the life span extension caused by germline removal, and overexpression of mir-71 further extends th ...[more]

PMID: 22482727

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Project description:FoxO transcription factors promote longevity across taxa. How they do so is poorly understood. In the nematode Caenorhabditis elegans, the A- and F-isoforms of the FoxO transcription factor DAF-16 extend life span in the context of reduced DAF-2 insulin-like growth factor receptor (IGFR) signaling. To elucidate the mechanistic basis for DAF-16/FoxO-dependent life span extension, we performed an integrative analysis of isoform-specific daf-16/FoxO mutants. In contrast to previous studies suggesting that DAF-16F plays a more prominent role in life span control than DAF-16A, isoform-specific daf-16/FoxO mutant phenotypes and whole transcriptome profiling revealed a predominant role for DAF-16A over DAF-16F in life span control, stress resistance, and target gene regulation. Integration of these datasets enabled the prioritization of a subset of 92 DAF-16/FoxO target genes for functional interrogation. Among 29 genes tested, two DAF-16A-specific target genes significantly influenced longevity. A loss-of-function mutation in the conserved gene gst-20, which is induced by DAF-16A, reduced life span extension in the context of daf-2/IGFR RNAi without influencing longevity in animals subjected to control RNAi. Therefore, gst-20 promotes DAF-16/FoxO-dependent longevity. Conversely, a loss-of-function mutation in srr-4, a gene encoding a seven-transmembrane-domain receptor family member that is repressed by DAF-16A, extended life span in control animals, indicating that DAF-16/FoxO may extend life span at least in part by reducing srr-4 expression. Our discovery of new longevity genes underscores the efficacy of our integrative strategy while providing a general framework for identifying specific downstream gene regulatory events that contribute substantially to transcription factor functions. As FoxO transcription factors have conserved functions in promoting longevity and may be dysregulated in aging-related diseases, these findings promise to illuminate fundamental principles underlying aging in animals.

Dataset Information

The C. elegans microRNA mir-71 acts in neurons to promote germline-mediated longevity through regulation of DAF-16/FOXO.

Publications

The C. elegans microRNA mir-71 acts in neurons to promote germline-mediated longevity through regulation of DAF-16/FOXO.

Similar Datasets

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