PHA-4/Foxa mediates diet-restriction-induced longevity of C. elegans.
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.
Panowski
Siler H
SH
The Salk Institute for Biological Studies, Molecular and Cell Biology Laboratory, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
Wolff
Suzanne
S
Aguilaniu
Hugo
H
Durieux
Jenni
J
Dillin
Andrew
A
D000375:Aging / Q000502:physiology; D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D031204:Caloric Restriction; D004032:Diet; D051858:Forkhead Transcription Factors; D018628:Gene Dosage; D008136:Longevity / Q000235:genetics / Q000502:physiology*; D005810:Multigene Family / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D015996:Survival Rate; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; C113277:Pha-4 protein, C elegans; D015534:Trans-Activators; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; D013482:Superoxide Dismutase