Nrf2 mediates cancer protection but not prolongevity induced by caloric restriction

Kevin J. Pearson, Kaitlyn N. Lewis, Nathan L. Price, Joy W. Chang, Evelyn Perez, Maria Victoria Cascajo, Kellie Tamashiro, Suresh Poosala, Anna Csiszar, Zoltan Ungvari, Thomas W Kensler, Masayuki Yamamoto, Josephine M. Egan, Dan L. Longo, Donald K. Ingram, Placido Navas, Rafael De Cabo

Research output: Contribution to journalArticle

Abstract

Caloric restriction (CR) is the most potent intervention known to both protect against carcinogenesis and extend lifespan in laboratory animals. A variety of anticarcinogens and CR mimetics induce and activate the NF-E2-related factor 2 (Nrf2) pathway. Nrf2, in turn, induces a number of antioxidative and carcinogen-detoxifying enzymes. Thus, Nrf2 offers a promising target for anticarcinogenesis and antiaging interventions. We used Nrf2-disrupted (KO) mice to examine its role on the biological effects of CR. Here, we show that Nrf2 is responsible for most of the anticarcinogenic effects of CR, but is dispensable for increased insulin sensitivity and lifespan extension. Nrf2-deficient mice developed tumors more readily in response to carcinogen exposure than did WT mice, and CR was ineffective in suppressing tumors in the KO mice. However, CR extended lifespan and increased insulin sensitivity similarly in KO and WT mice. These findings identify a molecular pathway that dissociates the prolongevity and anticarcinogenic effects of CR.

Original languageEnglish (US)
Pages (from-to)2325-2330
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number7
DOIs
StatePublished - Feb 19 2008

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NF-E2-Related Factor 2
Caloric Restriction
Anticarcinogenic Agents
Neoplasms
Carcinogens
Insulin Resistance
Laboratory Animals
Carcinogenesis
Enzymes

Keywords

  • Aging
  • Carcinogenesis
  • Oxidative stress

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Nrf2 mediates cancer protection but not prolongevity induced by caloric restriction. / Pearson, Kevin J.; Lewis, Kaitlyn N.; Price, Nathan L.; Chang, Joy W.; Perez, Evelyn; Cascajo, Maria Victoria; Tamashiro, Kellie; Poosala, Suresh; Csiszar, Anna; Ungvari, Zoltan; Kensler, Thomas W; Yamamoto, Masayuki; Egan, Josephine M.; Longo, Dan L.; Ingram, Donald K.; Navas, Placido; De Cabo, Rafael.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 7, 19.02.2008, p. 2325-2330.

Research output: Contribution to journalArticle

Pearson, KJ, Lewis, KN, Price, NL, Chang, JW, Perez, E, Cascajo, MV, Tamashiro, K, Poosala, S, Csiszar, A, Ungvari, Z, Kensler, TW, Yamamoto, M, Egan, JM, Longo, DL, Ingram, DK, Navas, P & De Cabo, R 2008, 'Nrf2 mediates cancer protection but not prolongevity induced by caloric restriction', Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 7, pp. 2325-2330. https://doi.org/10.1073/pnas.0712162105
Pearson, Kevin J. ; Lewis, Kaitlyn N. ; Price, Nathan L. ; Chang, Joy W. ; Perez, Evelyn ; Cascajo, Maria Victoria ; Tamashiro, Kellie ; Poosala, Suresh ; Csiszar, Anna ; Ungvari, Zoltan ; Kensler, Thomas W ; Yamamoto, Masayuki ; Egan, Josephine M. ; Longo, Dan L. ; Ingram, Donald K. ; Navas, Placido ; De Cabo, Rafael. / Nrf2 mediates cancer protection but not prolongevity induced by caloric restriction. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 7. pp. 2325-2330.
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