Rejuvenation research最新文献

Caloric restriction (CR) is the most effective intervention for extending the life span of vertebrate and invertebrate aging models. Calorie restriction mimetics (CRMs), which are synthetic or natural chemicals that mimic the biochemical, hormonal, and physiological consequences of calorie restriction, are being researched for antiaging benefits. Baicalein is a plant-derived polyphenol that has the potential of antioxidant, anti-inflammatory, and autophagy inducer. The objective of this study is to evaluate the antiaging, anti-inflammatory, and antioxidant role of Baicalein in erythrocyte membrane and plasma, and evaluate the efficacy of Baicalein to act as a CRM candidate. This study evaluates the effect of Baicalein on aging biomarkers in normal and aged rats. We study various pro- and antioxidant markers, erythrocyte membrane transporters, and eryptosis. Baicalein supplementation in male Wistar rats significantly alleviated pro-oxidant markers and improved antioxidant profile. Improvement was also observed in age-induced alterations in membrane transporters, and eryptosis. Based on the aforementioned observations we conclude that Baicalein has the potential to maintain extracellular reactive oxygen species levels and redox homeostasis during the aging process, an effect that is similar to CR. Thus, Baicalein may be a potent CRM candidate for antiaging interventions.

Asymmetric division of stem cells is an evolutionarily conserved process in multicellular organisms responsible for maintaining cellular fate diversity. Symmetric-asymmetric division pattern of mesenchymal stem cells (MSCs) is regulated by both biochemical and biophysical cues. However, modulation of mechanotransduction pathway by varying scaffold properties and their adaptation to control stem cell division fate is not widely established. In this study, we explored the interplay between the mechanotransduction pathway and polarity protein complex in stem cell asymmetry under varied biophysical stimuli. We hypothesize that variation of scaffold stiffness will impart mechanical stimulus and control the cytoskeleton assembly through RhoA, which will lead to further downstream activation of polarity-related cell signaling and asymmetric division of MSCs. To establish the hypothesis, umbilical cord-derived MSCs were cultured on polycaprolactone/collagen scaffolds with varied stiffness, and expression levels of several important genes (viz., Yes-associated protein [YAP], transcriptional coactivator with PDZ-binding motif [TAZ], LATS1, LATS2, Par3, Par6, PRKC1 [homolog of aPKC] and RhoA), and biomarkers (viz. YAP, TAZ, F-actin, Numb) were assessed. Support vector machine polarity index was employed to understand the polarization status of the MSCs cultured on varied scaffold stiffness. Furthermore, the Bayesian logistic regression model was employed for classifying the asymmetric division of MSCs cultured on different scaffold stiffnesses that showed 91% accuracy. This study emphasizes the vital role of scaffold properties in modulating the mechanotransduction signaling pathway of MSCs and provides mechanistic basis for adopting facile method to control stem cell division pattern toward improving tissue engineering outcome.

Spilanthes acmella Murr., a well-known Thai traditional medicine, has been used for treatment of toothache, rheumatism, and fever. Diverse pharmacological activities of S. acmella Murr. have been reported. In this study, antioxidative and neuroprotective effects of S. acmella Murr. extracts as well as bioactive scopoletin, vanillic acid, and trans-ferulic acid found in the aerial parts of this plant species have been described. Protective effect of S. acmella Murr. extracts and bioactive compounds on dexamethasone-induced neuronal cell death was investigated. Different plant crude ethyl acetate (EtOAc) and methanol (MeOH) extracts including pure compounds of S. acmella Murr. were evaluated in human neuroblastoma SH-SY5Y cells. Cytotoxic effects were performed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Mechanisms involved in the antioxidant effects of S. acmella Murr. regarding the activation of antioxidant marker proteins such as superoxide dismutase 2 (SOD2) and sirtuin 3 (SIRT3) were determined using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) assay, Western blot analysis, and immunocytochemistry. Dexamethasone significantly caused the decrease of SH-SY5Y cell viability. Conversely, the increases in reactive oxygen species (ROS), autophagy, and apoptosis were observed in dexamethasone-treated cells. S. acmella Murr. MeOH and EtOAc extracts, as well as the bioactive compounds, reversed the toxic effect of dexamethasone by increasing the cell viability, SIRT3 protein expression but reducing the ROS, autophagy, and apoptosis. This study demonstrated that S. acmella Murr. may exert its protective effects against ROS through SOD2 and SIRT3 signaling pathways in dexamethasone-induced neurotoxicity. S. acmella Murr. may be a candidate therapy for neuroprotection.

Oxidative stress may be an important cause of erythrocyte senescence. Angiotensin II (Ang II) has recently been shown to promote vascular cell senescence. However, its effects on erythrocytes remain unclear. This study aims at investigating the role of Ang II in regulating erythrocyte lifespan through oxidative stress. Experiments were performed in C57/BL6J mice infused with Ang II (1500 ng/kg per minute) or saline for 7 days. After Ang II infusion, we found that Ang II increased erythrocyte number, hemoglobin, and red blood cell distribution width. These differences were accompanied by a decrease in glutathione (GSH) and an increase in malondialdehyde (MDA) concentration. In vitro, after 24 hours of Ang II treatment, erythrocytes showed reduced surface expression of CD47 and increased phosphatidylserine exposure. In parallel, Ang II reduced the levels of antioxidant enzymes, including Cu/ZnSOD, catalase, and peroxidase 2 (PRDX2). These effects were reversed by the addition of the antioxidant N-acetyl-L-cysteine or the Ang II type 1 (AT1) receptor blocker losartan. In addition, Ang II treatment increased pro-inflammatory oxylipin, including hydroxyeicosatetraenoic acids (HETEs) and dihydroxyoctadecenoic acids (DiHOMEs), in the erythrocyte membranes. Collectively, Ang II induced erythrocyte senescence and susceptibility to eryptosis, partially due to enhanced oxidative stress.

The development of senomorphic drugs to attenuate the senescent phenotype and senolytics to clear pro-inflammatory senescent cells (SCs) to treat aging-associated disorders is being hotly pursued. The effort is complicated by the fact that SCs play a constructive role in some cellular processes such as tissue repair and wound healing. However, concerns about efficacy, which SCs to target, and unwanted side effects have created potential roadblocks. Chimeric antigen receptor T cells directed against urokinase-type plasminogen activator receptor, which is expressed on at least a subset of SCs in atherosclerotic plaques and fibrotic livers, removed SC and improved glucose metabolism. A vaccine targeting CD153-expressing senescent T cells also improved glucose metabolism in obese mice. Recent work to selectively target SCs associated with several pathologies has resulted in the creation of a peptide vaccine that primarily targets endothelial cells expressing high levels of GPNMB, recently identified as a biomarker of senescence. The vaccine reduces atherosclerotic plaque burden and metabolic dysfunction such as glucose intolerance in mouse models of obesity and atherosclerosis. For translation to humans the activity of the vaccine will need to be tightly controlled, as the target GPNMB has multiple roles in normal physiology, including acting to inhibit and possibly resolve inflammation. A promising alternative approach would be to use passive immunization with a monoclonal antibody directed against GPNMB.