Article

Nature 447, 550-555 (31 May 2007) | doi:10.1038/nature05837; Received 6 September 2006; Accepted 12 April 2007; Published online 2 May 2007

PHA-4/Foxa mediates diet-restriction-induced longevity of C. elegans

Siler H. Panowski1, Suzanne Wolff1, Hugo Aguilaniu1,2, Jenni Durieux1 & Andrew Dillin1

  1. The Salk Institute for Biological Studies, Molecular and Cell Biology Laboratory, 10010 North Torrey Pines Road, La Jolla, California 92037, USA
  2. Present Address: Cellular and Organismal Aging Laboratory, Laboratoire de Biologie Moleculaire de la Cellule Ecole Normale Superieure de Lyon, 46 Allée d'Italie, 69364 Lyon, France.

Correspondence to: Andrew Dillin1 Correspondence and requests for materials should be addressed to A.D. (Email: dillin@salk.edu).

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Reduced food intake as a result of dietary restriction increases the lifespan of a wide variety of metazoans and delays the onset of multiple age-related pathologies. Dietary restriction elicits a genetically programmed response to nutrient availability that cannot be explained by a simple reduction in metabolism or slower growth of the organism. In the nematode worm Caenorhabditis elegans, the transcription factor PHA-4 has an essential role in the embryonic development of the foregut and is orthologous to genes encoding the mammalian family of Foxa transcription factors, Foxa1, Foxa2 and Foxa3. Foxa family members have important roles during development, but also act later in life to regulate glucagon production and glucose homeostasis, particularly in response to fasting. Here we describe a newly discovered, adult-specific function for PHA-4 in the regulation of diet-restriction-mediated longevity in C. elegans. The role of PHA-4 in lifespan determination is specific for dietary restriction, because it is not required for the increased longevity caused by other genetic pathways that regulate ageing.

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