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Resveratrol induces mitochondrial biogenesis and protects against metabolic decline, but whether SIRT1 mediates these benefits is the subject of debate. To circumvent the developmental defects of germline SIRT1 knockouts, we have developed an inducible system that permits whole-body deletion of SIRT1 in adult mice. Mice treated with a moderate dose of(More)
Rapamycin, an inhibitor of mechanistic target of rapamycin complex 1 (mTORC1), extends the life spans of yeast, flies, and mice. Calorie restriction, which increases life span and insulin sensitivity, is proposed to function by inhibition of mTORC1, yet paradoxically, chronic administration of rapamycin substantially impairs glucose tolerance and insulin(More)
Rapamycin, an inhibitor of mechanistic target of rapamycin (mTOR), has the strongest experimental support to date as a potential anti-aging therapeutic in mammals. Unlike many other compounds that have been claimed to influence longevity, rapamycin has been repeatedly tested in long-lived, genetically heterogeneous mice, in which it extends both mean and(More)
The dynamics of β-amyloid deposition and related second-order physiological effects, such as regional cerebral blood flow (rCBF), are key factors for a deeper understanding of Alzheimer's disease (AD). We present longitudinal in vivo data on the dynamics of β-amyloid deposition and the decline of rCBF in two different amyloid precursor protein (APP)(More)
Rapamycin, an inhibitor of mTOR complex 1 (mTORC1), improves insulin sensitivity in acute studies in vitro and in vivo by disrupting a negative feedback loop mediated by S6 kinase. We find that rapamycin has a clear biphasic effect on insulin sensitivity in C2C12 myotubes, with enhanced responsiveness during the first hour that declines to almost complete(More)
The molecular mechanisms of aluminum (Al) toxicity and tolerance in plants have been the focus of ongoing research in the area of stress phytophysiology. Recent studies have described Al-induced apoptosis-like cell death in plant and animal cells. In this study, we show that yeast (Saccharomyces cerevisiae) exposed to low effective concentrations of Al for(More)
This study evaluated the effects of a 5-HT4 agonist, cisapride, on neuronally evoked smooth muscle responses in bladder, urethra and ileum and compared these effects with those of an acetylcholinesterase inhibitor, distigmine. Electrical field stimulation (EFS) was applied to human bladder and ileum smooth muscle strips from human organ transplant donors(More)
Aromatase or cytochrome P450 (CYP19) enzyme catalyzes the rate-determining reaction in estrogen synthesis. Inhibiting aromatase is a major strategy in treating breast cancer patients. However, suppression on the transcriptional activity may be equally important in controlling aromatase. Dietary flavones and flavonones have been previously demonstrated to be(More)
Genistein is a phytoestrogen isolated from soyabean, and is a potential nutraceutical gearing for women suffering from perimenopausal symptoms. Because of its differential binding affinity to estrogen receptor (ER) isoforms, genistein is described as a selective estrogen receptor modulator (SERM). The ligand-receptor interaction is established, but the(More)
PURPOSE This study aims to investigate μ-calpain expression profiles in the anterior temporal neocortex in patients with intractable epilepsy, and to determine whether its pattern of expression is related to pathological changes seen in these patients. METHODS The study subjects consisted of 30 patients with intractable epilepsy and a control group of 10(More)