Description |
SRT 2104 is a brain-permeable activator of SIRT1, used for the research of type 2 diabetes mellitus and Huntington's disease.
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Related Catalog |
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Target |
SIRT1
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In Vitro |
SRT 2104 (3 μM) reduces p65/RelA acetylation levels in C2C12 cells[1].
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In Vivo |
SRT2104 (100 mg/kg, p.o.) improves whole-body physiology and extends lifespan in mice fed a standard diet. SRT2104 increases mitochondrial content and suppresses the inflammatory response in SD-fed mice. SRT2104 also changes the gene expression profile differently in liver and muscle. Short-term SRT2104 preserves muscle and bone mass[1]. 0.5% SRT2104 diet penetrates the blood-brain barrier, attenuates brain atrophy, improves motor function, and extends survival in a mouse model of Huntington's disease[2].
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Cell Assay |
C2C12 cell line is cultured in low glucose Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 10% fetal bovine serum (FBS) and penicillin-streptomycin. Cells are treated with vehicle (0.1% DMSO) or 3 μm SRT2104 for 24 h and then harvested for protein and Western blotting[1].
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Animal Admin |
For the longevity study, diets are started at 28 weeks of age after randomization into two groups of 100 mice per group. Mice are fed a standard AIN-93G diet (SD; carbohydrate:protein:fat ratio of 64:19:17 percent of kcal), or a SD supplemented with SRT2104. SRT2104 is added at a dose of 1.33 g drug per kg of chow, formulated to provide daily doses of 100 mg drug/kg bodyweight. For the hindlimb suspension study, starting at 4 months of age, C57BL/6 mice are fed either a standard AIN-93G diet (SD; carbohydrate:protein:fat ratio of 64:19:17 percent of kcal) or a SD supplemented with SRT2104 for 4 weeks prior to suspension, and then for an additional 2 weeks during the suspension. Diets are formulated so mice receive a daily dose of 200 mg drug/kg of bodyweight. For the 48-h fasting study, mice are fed either SD or a SD supplemented with SRT2104 (100 mg/kg) for 6 weeks prior to sacrifice. This is the same diet as for the longevity study mice. For the whole-body SIRT1 knockout and muscle-specific SIRT1 knockout mouse models, mice are maintained on house chow (carbohydrate:protein:fat ratio of 58:24:18 percent of kcal) for the course of their lives[1].
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References |
[1]. Mercken EM, et al. SRT2104 extends survival of male mice on a standard diet and preserves bone and muscle mass. Aging Cell. 2014 Oct;13(5):787-96. [2]. Jiang M, et al. Sirtuin 1 activator SRT2104 protects Huntington's disease mice. Ann Clin Transl Neurol. 2014 Dec;1(12):1047-52.
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