Regulation of Nrf2 signaling and longevity in naturally long-lived rodents
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- Kaitlyn N. Lewis
- Departments of Cellular and Structural Biology and
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- Emily Wason
- Physiology and
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- Yael H. Edrey
- Physiology and
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- Deborah M. Kristan
- Department of Biological Sciences, California State University, San Marcos, CA 92096; and
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- Eviatar Nevo
- Institute of Evolution, University of Haifa, Haifa 31905, Israel
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- Rochelle Buffenstein
- Departments of Cellular and Structural Biology and
書誌事項
- 公開日
- 2015-03-09
- 権利情報
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- http://www.pnas.org/site/misc/userlicense.xhtml
- DOI
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- 10.1073/pnas.1417566112
- 公開者
- Proceedings of the National Academy of Sciences
この論文をさがす
説明
<jats:title>Significance</jats:title> <jats:p>Both genetically altered and naturally long-lived mammals are more resistant to toxic compounds that may cause cancer and age-associated diseases than their shorter-lived counterparts. The mechanisms by which this stress resistance occurs remain elusive. We found that longer-lived rodent species had markedly higher levels of signaling activity of the multifunctional regulator nuclear factor erythroid 2-related factor (Nrf2) and that this increase in cytoprotective signaling appeared to be due to species differences in Kelch-like ECH-Associated Protein 1 (Keap1) and β-transducin repeat-containing protein (βTrCP) regulation of Nrf2 activity. Both of these negative regulators of Nrf2-signaling activity are significantly lower in longer-lived species. By targeting the proteins that regulate Nrf2 rather than Nrf2 itself, we may be able to identify new therapies that impact aging and age-associated diseases such as cancer.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 112 (12), 3722-3727, 2015-03-09
Proceedings of the National Academy of Sciences
