BACKGROUND: FoxA factors are critical regulators of embryonic development and postembryonic life, but little is know about the upstream pathways that modulate their activity [1]. C. elegans
pha-4 encodes a FoxA transcription factor that is required to establish the foregut in embryos and to control growth and longevity after birth [2-5]. We previously identified the AAA+ ATPase homolog
ruvb-1 as a potent suppressor of
pha-4 mutations [6]. RESULTS: Here we show that
ruvb-1 is a component of the Target of Rapamycin (TOR) pathway in C. elegans (CeTOR). Both
ruvb-1 and
let-363/TOR control nucleolar size and promote localization of box C/D snoRNPs to nucleoli, suggesting a role in rRNA maturation. Inactivation of
let-363/TOR or
ruvb-1 suppresses the lethality associated with reduced
pha-4 activity. The CeTOR pathway controls protein homeostasis and also contributes to adult longevity [7, 8]. We find that
pha-4 is required to extend adult lifespan in response to reduced CeTOR signaling. Mutations in the predicted CeTOR target
rsks-1/S6 kinase or in
ife-2/eIF4E also reduce protein biosynthesis and extend lifespan [9-11], but only
rsks-1 mutations require
pha-4 for adult longevity. In addition,
rsks-1, but not
ife-2, can suppress the larval lethality associated with
pha-4 loss-of-function mutations. CONCLUSIONS: The data suggest that
pha-4 and the CeTOR pathway antagonize one another to regulate postembryonic development and adult longevity. We suggest a model in which nutrients promote TOR and S6 kinase signaling, which represses
pha-4/FoxA, leading to a shorter lifespan. A similar regulatory hierarchy may function in other animals to modulate metabolism, longevity, or disease.