Deletion of Nrf2 shortens lifespan in C57BL6/J male mice but does not alter the health and survival benefits of caloric restriction

Laura C.D. Pomatto, Theresa Dill, Bethany Carboneau, Sophia Levan, Jonathan Kato, Evi M. Mercken, Kevin J. Pearson, Michel Bernier, Rafael de Cabo

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Caloric restriction (CR) is the leading non-pharmaceutical dietary intervention to improve health- and lifespan in most model organisms. A wide array of cellular pathways is induced in response to CR and CR-mimetics, including the transcriptional activator Nuclear factor erythroid-2-related factor 2 (Nrf2), which is essential in the upregulation of multiple stress-responsive and mitochondrial enzymes. Nrf2 is necessary in tumor protection but is not essential for the lifespan extending properties of CR in outbred mice. Here, we sought to study Nrf2-knockout (KO) mice and littermate controls in male C57BL6/J, an inbred mouse strain. Deletion of Nrf2 resulted in shortened lifespan compared to littermate controls only under ad libitum conditions. CR-mediated lifespan extension and physical performance improvements did not require Nrf2. Metabolic and protein homeostasis and activation of tissue-specific cytoprotective proteins were dependent on Nrf2 expression. These results highlight an important contribution of Nrf2 for normal lifespan and stress response.

Original languageEnglish
Pages (from-to)650-658
Number of pages9
JournalFree Radical Biology and Medicine
Volume152
DOIs
StatePublished - May 20 2020

Bibliographical note

Publisher Copyright:
© 2020 Elsevier Inc.

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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