A new DAF-16 isoform regulates longevity

Eun-Soo Kwon, Sri Devi Narasimhan, Kelvin Yen and Heidi A. Tissenbaum ()
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Eun-Soo Kwon: Program in Gene Function and Expression, University of Massachusetts Medical School
Sri Devi Narasimhan: Program in Gene Function and Expression, University of Massachusetts Medical School
Kelvin Yen: Program in Gene Function and Expression, University of Massachusetts Medical School
Heidi A. Tissenbaum: Program in Gene Function and Expression, University of Massachusetts Medical School

Nature, 2010, vol. 466, issue 7305, 498-502

Abstract: DAF-16d/f longevity factor FOXO (single forkhead box O) transcription factors have emerged as a major convergence point for the regulators of cell function, including the insulin/IGF1 signalling (IIS) pathway. The IIS is involved in various biological processes, including regulation of longevity. In the worm Caenorhabditis elegans, the FOXO transcription factor DAF-16a has a major role in the IIS pathway. DAF-16a is one of two isoforms and regulates the worm's longevity, stress response and dauer diapause, but it is not clear how DAF-16 achieves its specificity in regulating these various biological processes. Now a new DAF-16 isoform has been identified, DAF-16d/f, which is also important in the regulation of lifespan. A series of experiments involving gene-expression manipulation suggests that combinatorial interactions between the various DAF-16 isoforms act to fine-tune IIS-mediated processes in the context of the whole organism. C. elegans seems to use multiple isoforms from a single gene to fine-tune IIS-mediated processes, in contrast to the situation in mammals, where four different FOXO genes perform overlapping and distinct functions.

Date: 2010
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DOI: 10.1038/nature09184

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