Insulin receptor signalling pathways that influence life span. Binding of insulin leads to autophosphorylation and activation of the insulin receptor kinase (IR) and recruitment of insulin-receptor substrates (IRS-1, IRS-2). Phosphatidylinositol 3-kinase (PI3K) converts phosphatidylinositol(4,5)diphosphate (PI(4,5)P2) into phosphatidylinositol(3,4,5)triphosphate (PI(3,4,5)P3). This binds and activates phosphoinositide-dependent protein kinase 1 (PDK1), which phosphorylates the serine/threonine kinase Akt1. Akt1 is activated by binding to PI(3,4,5)P3 at the cell membrane and by phosphorylation. Akt1 stimulates the target of rapamycin (TOR or the mammalian mTOR) and protein synthesis but is an inhibitor of several other functions, including autophagy, SIRT1 activity and FOXO transcription factor activity. Insulin receptor signalling activity is downregulated by protein tyrosine phosphatase 1B (PTB1B), which dephosphorylates the IRK domain, and by the phosphatase and tensine homologue on chromosome 10 (PTEN) and SH2-domain-containing inositol phosphatase (SHIP2) both of which dephosphorylate PI(3,4,5)P3. Hydrogen peroxide enhances the autophosphorylation of IRK and inhibits the activity of the three phosphatases.