Fig. 1. Conserved longevity-regulatory components of insulin/IGF-1 signaling pathway in C. elegans and D. melanogaster. Insulin-like peptides (ILPs in Caenorhabditis elegans and DILPs in Drosophila melanogaster) bind to insulin/IGF-1 receptor (DAF-2 in C. elegans and dInR in D. melanogaster) and lead to its phosphorylation. Inhibition of insulin/IGF-1 receptor results in decreased binding to the insulin receptor substrate (IST-1 in C. elegans and CHICO in D. melanogaster), which in turn decreases the activity of phosphoinositide-3 kinase (AGE-1 in C. elegans and PI3K in D. melanogaster) that converts PIP2 to PIP3; conversely, the PTEN phosphatase (DAF-18 in C. elegans and dPTEN in D. melanogaster) functions to antagonize the activity of the phosphoinositide-3 kinase by converting PIP3 to PIP2. Decreased PIP3 levels lead to decreased activities of phosphoinositide-dependent kinase 1 (PDK-1 in C. elegans and dPDK1 in D. melanogaster) and the serine/threonine-specific protein kinase B (AKT-1/-2 in C. elegans and dAkt1 in D. melanogaster), and the activation of downstream transcription factor FOXO (DAF-16 in C. elegans and dFOXO in D. melanogaster). Reduced insulin/IGF-1 signaling in C. elegans also increases the activities of heat shock transcription factor-1 (HSF-1) and SKN-1 (NRF2). These transcription factors regulate the expression of target genes, which contribute to longevity.
