Shambhoo Sharan Tripathi, Raushan Kumar, Akalabya Bissoyi, Syed Ibrahim Rizvi
{"title":"Baicalein May Act as a Caloric Restriction Mimetic Candidate to Improve the Antioxidant Profile in a Natural Rodent Model of Aging.","authors":"Shambhoo Sharan Tripathi, Raushan Kumar, Akalabya Bissoyi, Syed Ibrahim Rizvi","doi":"10.1089/rej.2021.0071","DOIUrl":"https://doi.org/10.1089/rej.2021.0071","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":20979,"journal":{"name":"Rejuvenation research","volume":" ","pages":"70-78"},"PeriodicalIF":2.6,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40313838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ankita Das, Shreya Adhikary, Amit Roy Chowdhury, Ananya Barui
{"title":"Leveraging Substrate Stiffness to Promote Stem Cell Asymmetric Division via Mechanotransduction-Polarity Protein Axis and Its Bayesian Regression Analysis.","authors":"Ankita Das, Shreya Adhikary, Amit Roy Chowdhury, Ananya Barui","doi":"10.1089/rej.2021.0039","DOIUrl":"https://doi.org/10.1089/rej.2021.0039","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":20979,"journal":{"name":"Rejuvenation research","volume":" ","pages":"59-69"},"PeriodicalIF":2.6,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40313932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"On the Road to More Effective Rejuvenation Research.","authors":"Irina Conboy","doi":"10.1089/rej.2022.29006.irc","DOIUrl":"https://doi.org/10.1089/rej.2022.29006.irc","url":null,"abstract":"","PeriodicalId":20979,"journal":{"name":"Rejuvenation research","volume":"25 2 1","pages":"57-58"},"PeriodicalIF":2.6,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48781250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Carnosine improves cognitive impairment through promoting SIRT6 expression and inhibiting ER stress in a diabetic encephalopathy model.","authors":"Dong Peng, Xia Qing, L. Guan, Hong-ying Li, Lijun Qiao, Yun-bo Chen, Ye-Feng Cai, Qi Wang, Shi-Jie Zhang","doi":"10.1089/rej.2022.0002","DOIUrl":"https://doi.org/10.1089/rej.2022.0002","url":null,"abstract":"Diabetic encephalopathy is one of complications of diabetes mellitus. Carnosine is a dipeptide composed of β-alanine and L-histidine. Study has shown that carnosine could ameliorate cognitive impairment in animal model with diabetes mellitus. However, the mechanism remains unclear. An animal model of type 2 diabetes (db/db mice) was used in this study. The animals were treated with 0.9 % saline or carnosine (100 mg/kg) for 8 weeks. Morris water maze was tested after drug administration. Oxidative stress-related factors malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), and pro-inflammatory factors inducible nitric oxide synthase (iNOS) were measured. Synapse-related protein postsynapticdensity 95 (PSD95) and brain-derived neurotrophic factor (BDNF) were detected by western blot. Besides, the expressions of sirtuin 6 (SIRT6), binding immunoglobulin protein (BIP), protein kinase R-like endoplasmic reticulum kinase (PERK), phospho-protein kinase R-like endoplasmic reticulum kinase (P-PERK), inositol-requiring enzyme-1α (IRE1α), phospho-inositol-requiring enzyme-1α (P-IRE1α), activating transcription factor 6 (ATF6), C/EBP-homologous protein (CHOP) in the hippocampus of the brain were detected. The results showed that treatment with carnosine ameliorated cognitive impairment in db/db mice. Carnosine reduced neuronal oxidative stress damage and iNOS expression in db/db mice. Meanwhile, carnosine relieved neurodegeneration in the hippocampus of db/db mice. Furthermore, carnosine promoted the expression of SIRT6 and reduced the expressions of endoplasmic reticulum (ER) related factors (BIP, P-PERK, P-IRE1α, ATF6, CHOP). In conclusion, these data suggested that the protective effect of carnosine against diabetic encephalopathy might be related to SIRT6/ER stress pathway.","PeriodicalId":20979,"journal":{"name":"Rejuvenation research","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2022-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44165737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"It is time to work on the extension of body growth and reproductive stages.","authors":"W. Gu","doi":"10.1089/rej.2022.0017","DOIUrl":"https://doi.org/10.1089/rej.2022.0017","url":null,"abstract":"There are three major changes for the human lifespan in the past half decade: the decreased age of sexual maturity, slight increase in age of menopause/ andropause, and a trend of increase in life expectancy. The ages of puberty and menopause are the transitions in life stages, such that early puberty leads to loss and late menopause leads to gain the lifespan. So far, the strategies for increased lifespan have been largely focused on the post-reproductive stage. These approaches are challenging and may at some point reach a plateau. It might be interesting to expand this focus to potentially delaying the puberty and extending the period of body growth, which might yield longer reproductive stages as well as the longer and healthier lifespan.","PeriodicalId":20979,"journal":{"name":"Rejuvenation research","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2022-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42650843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D. Lacedonia, N. Tartaglia, G. Scioscia, P. Soccio, G. Pavone, G. Moriondo, C. Gallo, M. F. Foschino Barbaro, A. Ambrosi
{"title":"Different expression of miRNA in the subcutaneous and visceral adipose tissue of obese subjects.","authors":"D. Lacedonia, N. Tartaglia, G. Scioscia, P. Soccio, G. Pavone, G. Moriondo, C. Gallo, M. F. Foschino Barbaro, A. Ambrosi","doi":"10.1089/rej.2022.0004","DOIUrl":"https://doi.org/10.1089/rej.2022.0004","url":null,"abstract":"Obesity is a pathology characterized by an excessive accumulation of adipose tissue and it is a condition associated with complex alterations affecting different organs and systems. Obesity has great influences on cardiovascular and respiratory morbidity and mortality and impairs the multiple aspects of metabolism. Since micro-RNAs (miRNAs) are thought to play a role in the regulation of various pathological processes, in this complex framework, the investigation of these classes of noncoding regulatory RNA seems to be promising. Selected group of obese subjects was recruited. We analysed the expression of seven miRNAs from obese adipose tissue supposed to have a role in the pathogenesis of cardiovascular and respiratory disease related to obesity and we compared it with the expression of the same miRNAs in a group of non-obese controls. In the current study what emerged is miR-27b and miR-483 significant down-regulation in subcutaneous adipose tissue from obese group compared with non-obese ones. For visceral adipose tissue, a significant decrease in miR-27b and miR-223 expression was observed in obese group. Moreover, a different expression of miR-26a and miR-338 in the obese group was found. Those findings could help the individuation of previously unknown key players in the development of different diseases usually associated with obesity, such as cardiovascular and pulmonary diseases.","PeriodicalId":20979,"journal":{"name":"Rejuvenation research","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2022-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47334987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Protective Efficacy of <i>Spilanthes acmella</i> Murr. Extracts and Bioactive Constituents in Neuronal Cell Death.","authors":"Wilasinee Suwanjang, Chayanit Sirisuwat, Sujittra Srisung, Chartchalerm Isarankura-Na-Ayudhya, Supitcha Pannengpetch, Supaluk Prachayasittikul","doi":"10.1089/rej.2021.0002","DOIUrl":"https://doi.org/10.1089/rej.2021.0002","url":null,"abstract":"<p><p><i>Spilanthes acmella</i> Murr., a well-known Thai traditional medicine, has been used for treatment of toothache, rheumatism, and fever. Diverse pharmacological activities of <i>S. acmella</i> Murr. have been reported. In this study, antioxidative and neuroprotective effects of <i>S. acmella</i> Murr. extracts as well as bioactive scopoletin, vanillic acid, and <i>trans</i>-ferulic acid found in the aerial parts of this plant species have been described. Protective effect of <i>S. acmella</i> 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 <i>S. acmella</i> 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 <i>S. acmella</i> 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. <i>S. acmella</i> 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 <i>S. acmella</i> Murr. may exert its protective effects against ROS through SOD2 and SIRT3 signaling pathways in dexamethasone-induced neurotoxicity. <i>S. acmella</i> Murr. may be a candidate therapy for neuroprotection.</p>","PeriodicalId":20979,"journal":{"name":"Rejuvenation research","volume":"25 1","pages":"2-15"},"PeriodicalIF":2.6,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39693300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rejuvenation researchPub Date : 2022-02-01Epub Date: 2022-01-28DOI: 10.1089/rej.2021.0054
Chenglin Huang, Jing Gao, Tong Wei, Weili Shen
{"title":"Angiotensin II-Induced Erythrocyte Senescence Contributes to Oxidative Stress.","authors":"Chenglin Huang, Jing Gao, Tong Wei, Weili Shen","doi":"10.1089/rej.2021.0054","DOIUrl":"https://doi.org/10.1089/rej.2021.0054","url":null,"abstract":"<p><p>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. <i>In vitro</i>, 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.</p>","PeriodicalId":20979,"journal":{"name":"Rejuvenation research","volume":"25 1","pages":"30-38"},"PeriodicalIF":2.6,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39886570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Changing of the Guard: Our First Editorial.","authors":"Irina Conboy","doi":"10.1089/rej.2022.29005.irc","DOIUrl":"https://doi.org/10.1089/rej.2022.29005.irc","url":null,"abstract":"","PeriodicalId":20979,"journal":{"name":"Rejuvenation research","volume":"25 1","pages":"1"},"PeriodicalIF":2.6,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39931462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Antiaging Vaccines Targeting Senescent Cells.","authors":"Andrew R Mendelsohn, James W Larrick","doi":"10.1089/rej.2022.0008","DOIUrl":"https://doi.org/10.1089/rej.2022.0008","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":20979,"journal":{"name":"Rejuvenation research","volume":"25 1","pages":"39-45"},"PeriodicalIF":2.6,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39723353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}