Deletion of Nrf2 Shortens Lifespan in C57BL6/J Male Mice but does not Alter the Health and Survival Benefits of Caloric Restriction
| Autor: | Laura Corrales-Diaz Pomatto, Michel Bernier, Sophia R. Levan, Evi M. Mercken, Jonathan Kato, Kevin J. Pearson, Rafael de Cabo, Theresa Dill, Bethany A. Carboneau |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
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 |
| Zdroj: | Free Radic Biol Med |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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