title: The role of the antioxidant and longevity-promoting Nrf2 pathway in metabolic regulation.
abstract: OBJECTIVE
  The vertebrate cap'n'collar family transcription factor Nrf2 and its invertebrate homologues SKN-1 (in worms) and CncC (in flies) function as master mediators of antioxidant and detoxification responses and regulators of the cellular redox state. Nrf2 controls gene expression programs that defend various tissues against diverse electrophilic stressors and oxidative insults, thus protecting the organism from disorders that are caused or exacerbated by such stresses. Moreover, studies on model organisms implicate the Nrf2 pathway in the prevention of aging-related diseases and suggest that SKN-1-regulated and CncC-regulated gene expression can promote longevity. These facets of Nrf2 signaling have been thoroughly reviewed. This article discusses another aspect of the Nrf2 pathway's function that has not yet received the same degree of attention, but emerges as a topic of increasing interest and potential clinical impact: its role in metabolic regulation and its interaction with central signaling systems that respond to nutritional inputs.
  
  
  RESULTS
  Recent evidence identifies Nrf2 signaling as a mediator of the salutary effects of caloric restriction. Nrf2 signaling also crosstalks with metabolic signaling systems such as the insulin/Akt pathway as well as with the metabolism of lipids. Moreover, Nrf2 has a protective role in models of diabetic nephropathy.
  
  
  CONCLUSIONS
  The emerging role of Nrf2 as an effector of metabolic and longevity signals offers new therapeutic perspectives. The potential impact of pharmacological manipulation of Nrf2 signaling as a strategy for the prevention and treatment of metabolic disease can be envisioned.
authors.affiliation: Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, New York, USA.
authors.forename: Gerasimos P
authors.initials: GP
authors.lastname: Sykiotis
authors.forename: Ioannis G
authors.initials: IG
authors.lastname: Habeos
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Samuelson
authors.forename: Dirk
authors.initials: D
authors.lastname: Bohmann
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D031204:Caloric Restriction; D003928:Diabetic Nephropathies; D004734:Energy Metabolism; D015870:Gene Expression; D005786:Gene Expression Regulation; D008136:Longevity; D008659:Metabolic Diseases / Q000235:genetics / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D014157:Transcription Factors