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Deletion of Nrf2 Shortens Lifespan in C57BL6/J Male Mice but does not Alter the Health and Survival Benefits of Caloric Restriction
- Source :
- Free Radic Biol Med
- Publication Year :
- 2020
-
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.
- 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
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Free Radic Biol Med
- Accession number :
- edsair.doi.dedup.....931e943f661f7b7882beff639cadb838