1. Deletion of Nrf2 Shortens Lifespan in C57BL6/J Male Mice but does not Alter the Health and Survival Benefits of Caloric Restriction
- Author
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Laura Corrales-Diaz Pomatto, Michel Bernier, Sophia R. Levan, Evi M. Mercken, Jonathan Kato, Kevin J. Pearson, Rafael de Cabo, Theresa Dill, and Bethany A. Carboneau
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,NF-E2-Related Factor 2 ,ved/biology.organism_classification_rank.species ,Longevity ,Male mice ,Biology ,Biochemistry ,digestive system ,environment and public health ,Article ,C57bl6 j ,Fight-or-flight response ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Downregulation and upregulation ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,Model organism ,Caloric Restriction ,Mitochondrial enzymes ,Mice, Knockout ,ved/biology ,Caloric theory ,respiratory system ,Mice, Inbred C57BL ,030104 developmental biology ,Endocrinology ,Tumor protection ,030217 neurology & neurosurgery - 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.
- Published
- 2020