Aim: Silencing information regulator (SirT1), a NAD-dependent histone deacetylase, is an essential mediator of longevity in normal cells by calorie restriction. SirT1 has many biological functions, including transcription regulation, cell differentiation inhibition, cell cycle regulation, and anti-apoptosis. Resveratrol (RV)-induced SirT1 activation also improves endothelial dysfunction and suppresses vascular inflammation. In this study, we investigated the roles of RV-induced SirT1 activation in endothelial cells under oxidative stress. Methods: SirT1 mRNA expression levels were examined in the endothelium layer (endothelial cells) of cardiac coronary vessels from patients receiving coronary artery bypass graft surgery (CABG) surgery and aged rats using reverse transcriptase polymerase chain reaction (RT-PCR). To further explore the effect of SirT1 activation on oxidative stress-induced aging, senescence-associated β-galactosidase (SA-β-gal) expression in RV-treated human umbilical vein endothelial cells (HUVECs) with or without H2O2 treatment was evaluated. Results: SirT1 expression was decreased in aged and atherosclerotic vessels in vivo, and significantly reduced in endothelial cells purified from vessel tissues. Furthermore, SirT1 levels were dose-dependently increased in RV-treated HUVECs. The SA-β gal assay showed that RV inhibited the senescent phenotype of H2O2-treated HUVECs. Reactive oxygen species (ROS) production and the percentage of cells positive for SA-β gal were significantly increased in siRNA-SirT1 (knockdown of SirT1 expression)-treated HUVEC cells. Importantly, the treatment effect of RV was significantly abolished in the oxidative effects of H2O2-treated HUVECs by siRNA-SirT1. Conclusion: Our data suggested that SirT1 could be a crucial factor involved in the endothelial cells of atherosclerotic CAGB patients and aging rats. RV is a potential candidate for preventing oxidative stress-induced aging in endothelial cells. RV may also prevent ROS-induced damage via increased endothelial SirT1 expression.

Resveratrol is a natural polyphenol antioxidant that has been shown to facilitate osteogenic differentiation. A recent breakthrough has demonstrated that ectopic expression of four genes is sufficient to reprogram murine and human fibroblasts into induced pluripotent stem (iPS) cells. However, the roles of resveratrol in the differentiation and cytoprotection of iPS cells have never been studied. In this study, we showed that, in addition to cardiac cells, neuron-like cells, and adipocytes, mouse iPS cells could differentiate into osteocyte-like cells. Using atomic force microscopy that provided nanoscale resolution, we monitored mechanical properties of living iPS cells during osteogenic differentiation. The intensity of mineralization and stiffness in differentiating iPS significantly increased after 14 days of osteogenic induction. Furthermore, resveratrol was found to facilitate osteogenic differentiation in both iPS and embryonic stem cells, as shown by increased mineralization, up-regulation of osteogenic markers, and decreased elastic modulus. Dexamethasone-induced apoptosis in iPS cell-derived osteocyte-like cells was effectively prevented by pretreatment with resveratrol. Furthermore, resveratrol significantly increased manganese superoxide dismutase expression and intracellular glutathione level, thereby efficiently decreasing dexamethasone-induced reactive oxygen species (ROS) production and cytotoxicity. Transplantation experiments using iPS cell-derived osteocyte-like cells further demonstrated that oral intake of resveratrol could up-regulate osteopontin expression and inhibit teratoma formation in vivo. In sum, resveratrol can facilitate differentiation of iPS cells into osteocyte-like cells, protect these iPS cell-derived osteocyte-like cells from glucocorticoid-induced oxidative damage, and decrease tumorigenicity of iPS cells. These findings implicate roles of resveratrol and iPS cells in the stem cell therapy of orthopedic diseases.

Muscle wasting, known to develop in patients with chronic kidney disease (CKD), is a deleterious consequence of numerous complications associated with deteriorated renal function. Muscle wasting in CKD mainly involves dysregulated muscle protein metabolism and impaired muscle cell regeneration. In this narrative review, we discuss the cardinal role of the insulin-like growth factor 1 and myostatin signaling pathways, which have been extensively investigated using animal and human studies, as well as the emerging concepts in microRNA- and gut microbiota-mediated regulation of muscle mass and myogenesis. To ameliorate muscle loss, therapeutic strategies, including nutritional support, exercise programs, pharmacological interventions, and physical modalities, are being increasingly developed based on advances in understanding its underlying pathophysiology.