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(Circulation Research. 2008;102:519.)
© 2008 American Heart Association, Inc.

Review

Mechanisms Underlying Caloric Restriction and Lifespan Regulation

Implications for Vascular Aging

Zoltan Ungvari, Cristina Parrado-Fernandez, Anna Csiszar, Rafael de Cabo

From the Department of Physiology (Z.U., A.C.), New York Medical College, Valhalla; Laboratory of Experimental Gerontology (C.P.-F., R.d.C.), National Institute on Aging, National Institutes of Health, Baltimore, Md; and Laboratorio de Biología Celular (C.P.-F.), Universidad de Córdoba, Spain.

Correspondence to Dr Rafael de Cabo, Laboratory of Experimental Gerontology, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Dr, Baltimore, MD 21224. E-mail decabora{at}grc.nia.nih.gov

This Review is part of a thematic series on the Biological Role of Senescence in Cardiovascular Disease, which includes the following articles:

Telomere Biology and Cardiovascular Disease

Vascular Cell Senescence: Contribution to Atherosclerosis

Stem Cells and the Regeneration of the Aging Cardiovascular System

Mechanisms of Cardiovascular Disease in Accelerated Aging Syndromes

Mechanisms Underlying Caloric Restriction and Lifespan Regulation: Implications for Vascular Aging
Issei Komuro Guest Editor

This review focuses on the emerging evidence that attenuation of the production of reactive oxygen species and inhibition of inflammatory pathways play a central role in the antiaging cardiovascular effects of caloric restriction. Particular emphasis is placed on the potential role of the plasma membrane redox system in caloric restriction–induced pathways responsible for sensing oxidative stress and increasing cellular oxidative stress resistance. We propose that caloric restriction increases bioavailability of NO, decreases vascular reactive oxygen species generation, activates the Nrf2/antioxidant response element pathway, inducing reactive oxygen species detoxification systems, exerts antiinflammatory effects, and, thereby, suppresses initiation/progression of vascular disease that accompany aging.

Key Words: aging • antioxidants • caloric restriction • nuclear receptors • redox

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