The role of the antioxidant and longevity-promoting Nrf2... : Current Opinion in Clinical Nutrition & Metabolic Care (original) (raw)
Ageing: biology and nutrition: Edited by Ronni Chernoff and Tommy Cederholm
Sykiotis, Gerasimos Pb; Habeos, Ioannis Gb; Samuelson, Andrew Va; Bohmann, Dirka
aDepartment of Biomedical Genetics, University of Rochester Medical Center, Rochester, New York, USA
bDivision of Endocrinology and Metabolism, Department of Internal Medicine, University of Patras Medical School, Patras, Greece
Correspondence to Dirk Bohmann, Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, New York, USA Tel: +1 585 273 1446; fax: +1 585 273 1450; e-mail: [email protected]
Current Opinion in Clinical Nutrition and Metabolic Care 14(1):p 41-48, January 2011. | DOI: 10.1097/MCO.0b013e32834136f2
Abstract
Purpose of review
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.
Recent findings
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.
Summary
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.
© 2011 Lippincott Williams & Wilkins, Inc.