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A new DAF-16 isoform regulates longevity

Author

Listed:
  • 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
    Program in Molecular Medicine, University of Massachusetts Medical School)

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.

Suggested Citation

  • Eun-Soo Kwon & Sri Devi Narasimhan & Kelvin Yen & Heidi A. Tissenbaum, 2010. "A new DAF-16 isoform regulates longevity," Nature, Nature, vol. 466(7305), pages 498-502, July.
    • Handle: RePEc:nat:nature:v:466:y:2010:i:7305:d:10.1038_nature09184
    DOI: 10.1038/nature09184
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    Cited by:

    1. Yan-Ping Zhang & Wen-Hong Zhang & Pan Zhang & Qi Li & Yue Sun & Jia-Wen Wang & Shaobing O. Zhang & Tao Cai & Cheng Zhan & Meng-Qiu Dong, 2022. "Intestine-specific removal of DAF-2 nearly doubles lifespan in Caenorhabditis elegans with little fitness cost," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    2. Jin-Hyuck Jeong & Jun-Seok Han & Youngae Jung & Seung-Min Lee & So-Hyun Park & Mooncheol Park & Min-Gi Shin & Nami Kim & Mi Sun Kang & Seokho Kim & Kwang-Pyo Lee & Ki-Sun Kwon & Chun-A. Kim & Yong Ryo, 2023. "A new AMPK isoform mediates glucose-restriction induced longevity non-cell autonomously by promoting membrane fluidity," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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