Aging is one of the most fundamental biological processes, whose rate is shown to be regulated, at least in part, by an evolutionarily conserved insulin/insulin-like growth factor-1 (IGF-1) signaling pathway. In C. elegans, this pathway comprising DAF-2 (insulin / IGF-1 receptor), AGE-1 (PI3-kinase), and AKT1/2 is shown to regulate lifespan through controlling the activity of DAF-16. Thus, DAF-16 transcriptional targets regulate the C. elegans lifespan. We surveyed the C. elegans genome to identify downstream targets of DAF-16 by searching for those genes that have one of the identified DAF-16 binding elements (DBE). Subsequent RT-PCR analyses of the identified genes showed that two genes reproducibly show a much higher expression level in long-lived
daf-2 and
age-1 mutants than in the wild type or the short-lived
daf-16 mutant. One is
scl-1, and the other is
bml-1. Here we report that a C. elegans homolog of mammalian beta-carotene 15, 15-monooxygenase, termed
bml-1, is a DAF-16 target gene and functions to extend longevity. Bml-1 is highly expressed in long-lived mutants
daf-2 and
age-1. The elevated expression of
bml-1 in long-lived
daf-2 mutants is required for their optimum long lifespan. Overexpression of
bml-1 in the wild-type animal increases its lifespan by 30 %. We then find that expression of
bml-1 is upregulated by feeding the wild-type worm with beta-carotene and that beta-carotene feeding extends the lifespan by more than 20 %. This extension is reduced by half by
bml-1 RNAi treatment. Moreover, beta-carotene feeding-induced upregulation of
bml-1 is minimal in a
daf-16 mutant, whose lifespan is increased only slightly by beta-carotene feeding. In addition, expression of
daf-16 is downregulated in
bml-1 RNAi treated worms, and beta-carotene feeding induces upregulation of
daf-16 expression, which is inhibited by
bml-1 RNAi treatment. Thus, expression of
bml-1 and that of
daf-16 are dependent on each other. These results define a novel mechanism of the action of beta-carotene that leads to lifespan extension through expression of the lifespan-regulating genes.