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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jul 31, 2018 |
| Title |
Overexpression of CYB5R3 and NQO1, two NAD+ producing enzymes, mimics aspects of caloric restriction |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Calorie restriction (CR) is one of the most robust means to improve health and survival in model organisms. CR imposes a metabolic program that leads to increased stress resistance and delayed onset of chronic diseases, including cancer. In rodents, CR induces the upregulation of two NADH-dehydrogenases, namely NAD(P)H:quinone oxidoreductase 1 (Nqo1) and cytochrome b5 reductase 3 (Cyb5r3), which provide electrons for energy metabolism. It has been proposed that this upregulation may be responsible for some of the beneficial effects of CR, and defects in their activity are linked to aging and several age-associated diseases. However, it is unclear whether changes in metabolic homeostasis solely through up-regulation of these NADH-dehydrogenases have a positive impact on health and survival. We generated a mouse that overexpresses both metabolic enzymes leading to phenotypes that resemble aspects of CR including a modest increase in lifespan, greater physical performance, a decrease in chronic inflammation, and importantly, protection against carcinogenesis, one of the main hallmarks of CR. Furthermore, these animals showed an enhancement of metabolic flexibility and a significant upregulation of the NAD+/sirtuin pathway. The results highlight the importance of these NAD+ producers for the promotion of health and extended lifespan.
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| Overall design |
A transgenic mouse overexpressing rat Nqo1 and rat Cyb5r3 reductases (RedTg), was created, and the liver transcriptomes of WT and RedTg mice (N=4 per condition) assayed.
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| Contributor(s) |
Diaz-Ruiz A, Lanasa M, Garcia J, Mora H, Fan F, Martin-Montalvo A, Di Francesco A, Calvo-Rubio M, Salvador-Pascual A, Aon MA, Fishbein KW, Pearson KJ, Villalba JM, Navas P, Bernier M, de Cabo R |
| Citation(s) |
29706024 |
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| Submission date |
Dec 20, 2017 |
| Last update date |
Jun 22, 2020 |
| Contact name |
Supriyo De |
| Organization name |
NIA-IRP, NIH
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| Department |
Laboratory of Genetics and Genomics
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| Lab |
Computational Biology & Genomics Core
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| Street address |
251 Bayview Blvd
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| City |
Baltimore |
| State/province |
Maryland |
| ZIP/Postal code |
21224 |
| Country |
USA |
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| Platforms (1) |
| GPL13912 |
Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Feature Number version) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA425944 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE108379_RAW.tar |
33.5 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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