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| Status |
Public on Aug 18, 2011 |
| Title |
SRT1720 extends healthspan and lifespan in diet-induced obese mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Activation of Sirt1, the mammalian homolog of an NAD+-dependent deacetylase known to modulate lifespan in lower organisms, is thought to hold promise as a strategy for delaying aging in mammals. SRT1720, a novel compound developed as a specific and potent activator of Sirt1, has shown promising effects to glucose homeostasis in short-term studies of rats and mice. Here we show SRT1720 extends both mean and maximum lifespan of mice fed a high-fat diet and has concrete benefits to health including reduced liver steatosis and increased insulin sensitivity and locomotor activity. Gene expression profiles and markers of inflammation and apoptosis were also restored to levels more reflective of standard diet controls. Furthermore, the benefits incurred by SRT1720 occurred in the absence of any observable toxicity. The current findings provide hope that safe and effective treatments may be developed to mitigate age-related diseases and enhance lifespan in humans.
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| Overall design |
Male C57BL/6J mice obtained at 12 weeks of age were maintained on a standard purified mouse diet (AIN-93G) until 56 weeks of age prior to the start of the experiment. Beginning at 56 weeks of age, the SD group was fed a standard AIN-93G diet for the duration of the study. Three separate groups were placed on a high-fat diet (HFD) (AIN-93G modified by the addition of hydrogenated coconut oil to provide 60% of calories from fat) or HFD + 30mg/kg body weight SRT1720 (HFD-L) or 100mg/kg body weight SRT1720 (HFD-H) and remained on those diets throughout the study. All mice were fed ad libitum. Food intake and body weight were measured biweekly for the duration of the study.
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| Contributor(s) |
Minor RK, Baur JA, Ward T, Csiszar A, Mercken EM, Abdelmohsen K, Shin Y, Canto C, Krawczyk M, Hubbard BP, Zhang Y, Lehrmann E, Swindell WR, Pearson KJ, Becker KG, Gorospe M, Egan JM, Talan MI, Auwerx J, Westphal CH, Ellis JL, Ungvari Z, Sinclair DA, Elliott PJ, de Cabo R |
| Citation(s) |
22355589 |
| Submission date |
Nov 19, 2009 |
| 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) |
| GPL6885 |
Illumina MouseRef-8 v2.0 expression beadchip |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA120447 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE19102_RAW.tar |
3.1 Mb |
(http)(custom) |
TAR |
| GSE19102_non-normalized.txt.gz |
6.4 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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