title: The thioredoxin TRX-1 regulates adult lifespan extension induced by dietary restriction in Caenorhabditis elegans.
abstract: Dietary restriction (DR) is the only environmental intervention known to extend adult lifespan in a wide variety of animal models. However, the genetic and cellular events that mediate the anti-aging programs induced by DR remain elusive. Here, we used the nematode Caenorhabditis elegans to provide the first in vivo evidence that a thioredoxin (TRX-1) regulates adult lifespan extension induced by DR. We found that deletion of the gene trx-1 completely suppressed the lifespan extension caused by mutation of eat-2, a genetic surrogate of DR in the worm. However, trx-1 deletion only partially suppressed the long lifespan caused by mutation of the insulin-like receptor gene daf-2 or by mutation of the sensory cilia gene osm-5. A trx-1::GFP translational fusion expressed from its own promoter in ASJ neurons (Ptrx-1::trx-1::GFP) rescued the trx-1 deletion-mediated suppression of the lifespan extension caused by mutation of eat-2. This rescue was not observed when trx-1::GFP was expressed from the ges-1 promoter in the intestine. In addition, overexpression of Ptrx-1::trx-1::GFP extended lifespan in wild type, but not in eat-2 mutants. trx-1 deletion almost completely suppressed the lifespan extension induced by dietary deprivation (DD), a non-genetic, nutrient-based model of DR in the worm. Moreover, DD upregulated the expression of a trx-1 promoter-driven GFP reporter gene (Ptrx-1::GFP) in ASJ neurons of aging adults, but not that of control Pgpa-9::GFP (which is also expressed in ASJ neurons). We propose that DR activates TRX-1 in ASJ neurons during aging, which in turn triggers TRX-1-dependent mechanisms to extend adult lifespan in the worm.
authors.affiliation: Karolinska Institute, Center for Biosciences at NOVUM, Department of Biosciences and Nutrition, S-141 83 Huddinge, Sweden.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Fierro-González
authors.forename: María
authors.initials: M
authors.lastname: González-Barrios
authors.forename: Antonio
authors.initials: A
authors.lastname: Miranda-Vizuete
authors.forename: Peter
authors.initials: P
authors.lastname: Swoboda
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D031204:Caloric Restriction; D004032:Diet; D017353:Gene Deletion; D008136:Longevity; D008957:Models, Genetic; D009474:Neurons / Q000378:metabolism*; D013879:Thioredoxins / Q000235:genetics / Q000502:physiology*
chemical_list: D029742:Caenorhabditis elegans Proteins; C508778:TRX-1 protein, C elegans; D013879:Thioredoxins