Regulation of aging and innate immunity in C. elegans.
The free-living soil nematode Caenorhabditis elegans is a versatile model for the study of the genetic regulation of aging and of host-pathogen interactions. Many genes affecting multiple processes, such as neuroendocrine signalling, nutritional sensing and mitochondrial functions, have been shown to play important roles in determining the lifespan of C. elegans. The DAF-2-mediated insulin signalling pathway is the major pathway that regulates aging in this nematode and this role appears universal; neuroendrocrine signalling also affects aging in Drosophila and mice. Recent studies have shown that the innate immune function in C. elegans is modulated by signalling from the TGF-beta-like, the p38 MAPK and the DAF-2 insulin pathways. The requirement for the DAF-2 pathway in modulating aging and immunity suggests that these processes may be linked at the molecular level. It is well known that as humans age, immunosenescence occurs in which there is a general degradation of immune efficiency. However, the molecular mechanisms involved in this process remain unclear. In this review, we discuss the molecular mechanisms that modulate aging and immune response and attempt to suggest molecular links between these two processes.
Department of Genetics, and Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305-5120, USA. LeoKurz@stanford.edu
C Leopold
CL
Kurz
Man-Wah
MW
Tan
D000375:Aging / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000502:physiology; D017209:Apoptosis / Q000502:physiology; D017173:Caenorhabditis elegans / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology; D051858:Forkhead Transcription Factors; D018507:Gene Expression Regulation, Developmental; D007113:Immunity, Innate / Q000276:immunology / Q000502:physiology*; D007814:Larva / Q000235:genetics / Q000276:immunology / Q000502:physiology; D008136:Longevity / Q000235:genetics / Q000276:immunology / Q000502:physiology; D008954:Models, Biological; D009113:Muramidase / Q000235:genetics / Q000502:physiology; D009479:Neuropeptides / Q000502:physiology; D011972:Receptor, Insulin / Q000235:genetics / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology; D049231:Saposins / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000502:physiology
D023181:Antimicrobial Cationic Peptides; D029742:Caenorhabditis elegans Proteins; C117509:Dbl-1 protein, C elegans; D051858:Forkhead Transcription Factors; D009479:Neuropeptides; D011956:Receptors, Cell Surface; D049231:Saposins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C108831:daf-16 protein, C elegans; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin; D048051:p38 Mitogen-Activated Protein Kinases; D009113:Muramidase