期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 152, 期 -, 页码 650-658出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2020.01.005
关键词
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资金
- Intramural Research Program of the National Institute on Aging/NIH
- NIH from the National Institute of General Medical Sciences of the National Institutes of Health [Fi2GM123963]
- NATIONAL INSTITUTE ON AGING [ZIAAG000361] Funding Source: NIH RePORTER
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.
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