Fig. 3

C. elegans cellular pathways and their crosstalk, relating to aging and the stress response. Shown (from left to right) are the insulin/insulin-like growth factor (IIS) signaling pathway, the mitochondrial signaling pathways, and the mechanistic target of rapamycin (TOR) pathway. Arrows indicate positive regulatory events and bars indicate inhibitory interactions. Purple block arrows represent interactions between the different pathways, whereas dashed purple block arrows indicate possible indirect interactions. The oval molecules and their corresponding mammalian homologs involved in IIS [28, 56, 62, 72] are as below: AGE-1/PI3K, phospatidylinositol-3-kinase; PDK-1, 3-phosphoinositide-dependent kinase 1 ortholog; SGK-1, a serine/threonine protein kinase that is orthologous to the mammalian serum- and glucocorticoid-inducible kinases (SGKs); Akt/PKB, the serine/threonine kinase; DAF-16/FOXO, forkhead box O (FOXO) transcription factor. Mitochondrial dysfunctions [90–96] are associated with apoptotic/programmed cell death (PCD), aberrant autophagic regulation, endoplasmic reticulum dysfunction, and intracellular calcium, including c-Jun N-terminal kinase (JNK) subgroup of mitogen-activated protein (MAP) kinases; CED-4, CED-9, and EGL-1 belong to a conserved genetic pathway to regulate apoptosis during C. elegans development [63]; PINK-1, a predicted serine/threonine kinase which is similar with human PINK1, PTEN-induced kinase-1; SKN-1/Nrf, skin in excess transcription factor 1/NF-E2-related factor; mtROS, mitochondrial reactive oxygen species; ATP, adenosine-5′-triphosphate; HIF-1, hypoxia-inducible transcription factor 1. Major molecules in TOR pathways include TSC1/2, tuberous sclerosis complexes 1 and 2; RHEB, Ras homolog enriched in brain; TOR, target of rapamycin kinase; GSK3, glycogen synthase kinase ortholog. See text in Table 1 for further details