title: Caenorhabditis elegans DAF-16/FOXO transcription factor and its mammalian homologs associate with age-related disease.
abstract: The insulin/IGF-1 signaling pathway is evolutionarily conserved and its function is mediated largely by FOXO transcription factors. Reduced insulin/IGF-1 signaling leads to translocation of FOXO proteins from the cytoplasm to the nucleus where they activate a set of genes that mediate oxidative stress, heat shock, and xenobiotic responses, innate immunity, metabolism, and autophagy. Disruptions in the insulin/IGF-1 signaling pathway affect lifespan in many species. Over the past two decades, the function of these FOXO proteins in age-related diseases has been extensively studied, in the model organism Caenorhabditis elegans as well as in humans. In this review we investigate the mechanisms by which FOXO proteins influence the development of age-related disease pathways in both species.
authors.affiliation: Laboratory of Nematology, Wageningen University, Droevendaalsesteeg 1, 6708PB Wageningen, The Netherlands.
authors.forename: Kylie
authors.initials: K
authors.lastname: Hesp
authors.affiliation: Laboratory of Nematology, Wageningen University, Droevendaalsesteeg 1, 6708PB Wageningen, The Netherlands.
authors.forename: Geert
authors.initials: G
authors.lastname: Smant
authors.affiliation: Laboratory of Nematology, Wageningen University, Droevendaalsesteeg 1, 6708PB Wageningen, The Netherlands. Electronic address: jan.kammenga@wur.nl.
authors.forename: Jan E
authors.initials: JE
authors.lastname: Kammenga
mesh_terms: D000375:Aging / Q000502:physiology*; D000544:Alzheimer Disease / Q000235:genetics; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D018869:Heat-Shock Response; D006801:Humans; D006816:Huntington Disease / Q000235:genetics; D007328:Insulin / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D010024:Osteoporosis / Q000235:genetics; D018384:Oxidative Stress; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C583557:IGF1 protein, human; D007328:Insulin; C108831:daf-16 protein, C elegans; D007334:Insulin-Like Growth Factor I
keywords: Age-related disease; Aging; C. elegans; Daf-16/FOXO; Human; Translational