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(Circulation Research. 2004;95:953.)
© 2004 American Heart Association, Inc.

Editorial

Sirviving Cardiac Stress

Cardioprotection Mediated by a Longevity Gene

Michael T. Crow

From the Department of Medicine, Johns Hopkins University, Baltimore, Md.

Correspondence to Michael T. Crow, PhD, Department of Medicine, Division of Pulmonary and Critical Care Medicine, Johns Hopkins Asthma and Allergy Center, 5A.58, 5501 Hopkins Bayview Circle, Baltimore, MD 21224. E-mail mcrow1@jhmi.edu

Key Words: cardioprotection • cardiac stress • insulin signaling

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Over the last decade, a number of genetic modifiers of yeast and animal lifespan have been discovered and studied in some detail. Many of these genes lie on or impinge on the evolutionarily conserved insulin signaling pathway.¹ In fact, one of the first genes discovered that was linked to lifespan regulation in Caenorhabditis elegans was DAF2, the product of which is highly related to mammalian insulin/insulin-like growth factor (IGF) receptors.² Many of the intermediates activated by insulin intracellular signaling, such as phosphatidylinositol 3' kinase (PI3K) and AKT/PKB, mediate cytoprotection associated not only with the insulin receptor but other receptor-mediated signaling pathways as well.³ Preventing the cell death that occurs in response to stress would seem to be a reasonable component of an overall cellular strategy for extending lifespan because the cumulative effects of cell loss have been implicated in various age-related disorders, including cardiovascular disease. Increased activity of prosurvival molecules through increased growth factor/insulin signaling would seem to be one way to achieve extension. Yet the lifespan extending-mutation in the C elegans DAF2 gene caused decreased, rather than increased, signaling. Although it seems counterintuitive that decreased prosurvival signaling is capable of extending lifespan, the notion is supported by the remarkable success that caloric restriction has had in increasing lifespan across the phylogenic spectrum.⁴ Here too lifespan extension is associated with reduced glucose, insulin, and IGF1 plasma levels, as well as reduced insulin signaling.⁵ Clearly, either the role of cytoprotection in lifespan extension has been overstated or the complexities of insulin . . . [Full Text of this Article]

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