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| Status |
Public on Dec 20, 2014 |
| Title |
The SIRT1 activator SRT1720 extends lifespan and improves health of mice fed a standard diet |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The prevention or delay of the onset of age-related diseases prolongs survival and improves quality of life while reducing the burden on the health care system. Activation of sirtuin 1 (SIRT1), an NAD+ deacetylase, improves metabolism and confers protection against physiological and cognitive disturbances in old age. SRT1720 is a specific SIRT1 activator that has health and lifespan benefits in adult mice fed a highfat diet. We found extension in lifespan, delayed onset of age-related metabolic diseases, and improved general health in mice fed a standard diet after SRT1720 supplementation. Inhibition of pro-inflammatory gene expression both in the liver and muscle of SRT1720-treated animals was noted. SRT1720 lowered phosphorylation of NF-κB pathway regulators in vitro only when SIRT1 was functionally present. Combined with our previous work, the current study further supports the beneficial effects of SRT1720 on health across the lifespan in mice.
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| Overall design |
Groups of 28 week old male C57BL/6J mice were maintained on ad libitum AIN-93G SD diet, or an ad libitum AIN-93G diet supplemented with SRT1720 for the rest of their lives. SRT1720 was added at a dose of 1.33 g drug per kg of chow, formulated to provide daily doses of approximately 100 mg drug per kg bodyweight to the mice. 5 mice from each group were selected and RNA was extracted from both muscle and liver tissue using 1.0mm glass beads in a Precellys 24 Tissue Homogenizer and Qiagen RNeasy Mini Kits for Fibrous Tissue according to manufacturer's specifications. Quality and quantity of the total RNA was checked with the Agilent 2100 bioanalyzer using RNA 6000 Nano chips. RNA samples were labeled using the Illumina TotalPrep RNA Amplification Kit. In short, 0.5ug of total RNA was first converted into single-stranded cDNA with reverse transcriptase using an oligo-dT primer containing the T7 RNA polymerase promoter site and then copied to produce double-stranded cDNA molecules. The double stranded cDNA was cleaned and concentrated with the supplied columns and used in an overnight in-vitro transcription reaction where single-stranded RNA (cRNA) was generated and labeled by incorporation of biotin-16-UTP. Arrays were hybridized using a total of 0.75ug of biotin-labeled cRNA at 58 degrees C for 16 hours to Illumina's Sentrix MouseRef-8 v2 Expression BeadChips. Each BeadChip has ~24,000 well-annotated RefSeq transcripts with approximately 30-fold redundancy. The arrays were washed, blocked and the biotin labeled cRNA was detected by staining with streptavidin-Cy3. Arrays were scanned at a resolution of 0.8um using the Beadstation 500 X from Illumina and the data was extracted using the Illumina GenomeStudio software(v1.6.0). Any spots at or below the background were filtered out using an Illumina detection p value of 0.02 and above. The natural log of all remaining scores were used to find the avg and std of each array and the z-score normalization was calculated and presented below. Z-score = (raw value - avg)/std.
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| Contributor(s) |
Mitchell SJ, Martin-Montalvo A, Mercken EM, Palacios HH, Ward TM, Minor RK, Vlasuk GP, Ellis JL, Sinclair DA, Bernier M, de Cabo R |
| Citation(s) |
24582957 |
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| Submission date |
Sep 18, 2013 |
| 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 (18)
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| GSM1191957 |
Muscle_Standard Diet_Replicate #4 |
| GSM1191958 |
Muscle_Standard Diet_Replicate #5 |
| GSM1191964 |
Liver_Standard Diet_Replicate #1 |
| GSM1191965 |
Liver_Standard Diet_Replicate #2 |
| GSM1191966 |
Liver_Standard Diet_Replicate #3 |
| GSM1191967 |
Liver_Standard Diet_Replicate #4 |
| GSM1191968 |
Liver_Standard Diet_Replicate #5 |
| GSM1234272 |
Muscle_Standard Diet plus SRT1720_Replicate #1 |
| GSM1234273 |
Muscle_Standard Diet plus SRT1720_Replicate #2 |
| GSM1234274 |
Muscle_Standard Diet plus SRT1720_Replicate #3 |
| GSM1234275 |
Muscle_Standard Diet plus SRT1720_Replicate #4 |
| GSM1234276 |
Liver_Standard Diet plus SRT1720_Replicate #1 |
| GSM1234277 |
Liver_Standard Diet plus SRT1720_Replicate #2 |
| GSM1234278 |
Liver_Standard Diet plus SRT1720_Replicate #3 |
| GSM1234279 |
Liver_Standard Diet plus SRT1720_Replicate #4 |
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| Relations |
| BioProject |
PRJNA219481 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE50987_RAW.tar |
3.1 Mb |
(http)(custom) |
TAR |
| GSE50987_non-normalized.txt.gz |
1.8 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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