Lessons from C. elegans: signaling pathways for longevity

Recent research using model organisms such as the nematode Caenorhabditis elegans has highlighted a crucial role for several conserved signaling pathways in longevity determination. Here, we review three major endocrine- and nutrient-sensing signaling pathways with influence on lifespan, the insulin/insulin-like growth factor (IGF), target of rapamycin (TOR), and germline signaling pathways. Although these pathways engage distinct sets of transcription factors, the three pathways appear to modulate aging in C. elegans through partially overlapping effector mechanisms, including lipid metabolism and autophagy. This review highlights the latest advances in our understanding of how the insulin/IGF-1, TOR, and germline signaling pathways utilize different transcription factors to modulate aging in C. elegans with special emphasis on the role of lipid metabolism and autophagy. Recent research using model organisms such as the nematode Caenorhabditis elegans has highlighted a crucial role for several conserved signaling pathways in longevity determination. Here, we review three major endocrine- and nutrient-sensing signaling pathways with influence on lifespan, the insulin/insulin-like growth factor (IGF), target of rapamycin (TOR), and germline signaling pathways. Although these pathways engage distinct sets of transcription factors, the three pathways appear to modulate aging in C. elegans through partially overlapping effector mechanisms, including lipid metabolism and autophagy. This review highlights the latest advances in our understanding of how the insulin/IGF-1, TOR, and germline signaling pathways utilize different transcription factors to modulate aging in C. elegans with special emphasis on the role of lipid metabolism and autophagy. C. elegans gene orthologs α subunit of AMP-activated kinase (AMPK). phosphatidylinositol 3-kinase. serine/threonine kinase Akt/PKB. cAMP response element-binding protein. CREB-regulated transcription coactivator-1. insulin/IGF-1 receptor. cytochrome P450 of the CYP27 subfamily. nuclear receptor FXR. TORC1-binding partner Raptor. transcription factor FOXO3A. phosphatidylinositol 3,4,5-triphosphate 3-phosphatase, PTEN. catalytic subunit of Rieske-like oxygenase. palmitoyl-CoA-Δ9-desaturase. stearoyl-CoA-Δ9-desaturase, SCD. 14-3-3 (FOXO-interacting) protein. Notch receptor. host cell factor 1. heat shock factor 1. one of 40 insulin-like peptides, encodes an insulin/IGF-1-like peptide. c-Jun N-terminal kinase. ankyrin-repeat protein KRIT-1. lipase with homology to human lysosomal acid lipase. mitogen-activated protein kinase. one of hundreds microRNA with a role in germline signaling. nuclear hormone receptor HNF-4. 3-phosphoinositide-dependent kinase 1. transcription factor FOXA. putative RNase-binding protein. protein arginine methyltransferase. Ras-related GTPase RagA. Ras-related GTPase RagC. Rheb GTPase. TORC2-binding partner Rictor (also referred to as lpo-6). E3 ubiquitin ligase. p70 ribosomal S6 kinase. transcription factor Nrf. suppressor of MEK. transcription elongation regulator homolog 1. target of rapamycin (also referred to as let-363). TOR complex 1. TOR complex 2. ULK-1 (Unc-51-like kinase).