Genetic control of longevity in C. elegans.
The nematode Caenorhabditis elegans has proven to be a very useful tool for studying the genetics of longevity. Over 70 genes have been found to influence lifespan in this worm. Those related to the Ins/IGF signaling pathway are among the best studied and will be focused on in this review. The master regulator of this pathway, the forkhead transcription factor DAF-16, can activate an enhanced life maintenance program in response to environmental and gonadal inputs. DAF-16 up- and downregulates expression of many genes leading to metabolic alterations and increased stress and microbial resistance. This is generally confirmed by biochemical and physiological data. Longevity mutants are not hypometabolic and probably produce more reactive oxygen species than wild type. However, their high antioxidant capacity may result in lower oxidative damage. Enhanced molecular turnover rates may also play a role in their longevity phenotype.
Braeckman
Bart P
BP
Biology Department, Ghent University, K.L.Ledeganckstraat 35, B-9000 Ghent, Belgium. Bart.Braeckman@UGent.be
Vanfleteren
Jacques R
JR
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth / Q000502:physiology*; D016678:Genome; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D008136:Longevity / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics
D029742:Caenorhabditis elegans Proteins; C064359:DAF-1 protein, C elegans; D007328:Insulin; D011956:Receptors, Cell Surface; D007334:Insulin-Like Growth Factor I