Mechanisms of Ageing and Development最新文献

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Current senolytics: Mode of action, efficacy and limitations, and their future 当前的老年药物:作用方式,疗效和局限性,以及它们的未来。
IF 5.3 3区 医学
Mechanisms of Ageing and Development Pub Date : 2023-11-29 DOI: 10.1016/j.mad.2023.111888
Amirhossein Nayeri Rad , Johannes Grillari
{"title":"Current senolytics: Mode of action, efficacy and limitations, and their future","authors":"Amirhossein Nayeri Rad ,&nbsp;Johannes Grillari","doi":"10.1016/j.mad.2023.111888","DOIUrl":"10.1016/j.mad.2023.111888","url":null,"abstract":"<div><p>Senescence is a cellular state characterized by its near-permanent halted cell cycle and distinct secretory phenotype. Although senescent cells have a variety of beneficial physiological functions, progressive accumulation of these cells due to aging or other conditions has been widely shown to provoke deleterious effects on the normal functioning of the same or higher-level biological organizations. Recently, erasing senescent cells in vivo, using senolytics, could ameliorate diseases identified with an elevated number of senescent cells. Since then, researchers have struggled to develop new senolytics each with different selectivity and potency. In this review, we have gathered and classified the proposed senolytics and discussed their mechanisms of action. Moreover, we highlight the heterogeneity of senolytics regarding their effect sizes, and cell type specificity as well as comment on the exploited strategies to improve these features. Finally, we suggest some prospective routes for the novel methods for ablation of senescent cells.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"217 ","pages":"Article 111888"},"PeriodicalIF":5.3,"publicationDate":"2023-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0047637423001148/pdfft?md5=8b939d9af255df7c110bb506e0ad98ac&pid=1-s2.0-S0047637423001148-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138470497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Protective effects of apigenin on the brain transcriptome with aging 芹菜素对衰老脑转录组的保护作用。
IF 5.3 3区 医学
Mechanisms of Ageing and Development Pub Date : 2023-11-24 DOI: 10.1016/j.mad.2023.111889
Alyssa N. Cavalier , Zachary S. Clayton , Devin Wahl , David A. Hutton , Cali M. McEntee , Douglas R. Seals , Thomas J. LaRocca
{"title":"Protective effects of apigenin on the brain transcriptome with aging","authors":"Alyssa N. Cavalier ,&nbsp;Zachary S. Clayton ,&nbsp;Devin Wahl ,&nbsp;David A. Hutton ,&nbsp;Cali M. McEntee ,&nbsp;Douglas R. Seals ,&nbsp;Thomas J. LaRocca","doi":"10.1016/j.mad.2023.111889","DOIUrl":"10.1016/j.mad.2023.111889","url":null,"abstract":"<div><p><span><span><span><span>Brain aging is associated with reduced cognitive function that increases the risk for dementia. Apigenin is a bioactive plant compound that inhibits </span>cellular aging processes and could protect against age-related </span>cognitive dysfunction, but its mechanisms of action in the brain have not been comprehensively studied. We characterized brain </span>transcriptome changes in young and old mice treated with apigenin in drinking water. We observed improved learning/memory in old treated mice, and our transcriptome analyses indicated that differentially expressed genes with aging and apigenin were primarily related to immune responses, inflammation, and cytokine regulation. Moreover, we found that genes/transcripts that were increased in old vs. young mice but downregulated with apigenin treatment in old animals were associated with immune activation/inflammation, whereas transcripts that were reduced with aging but increased with apigenin were related neuronal function and signaling. We also found that these transcriptome differences with aging and apigenin treatment were driven in part by </span>glial cells. To follow up on these in vivo transcriptome findings, we studied aged astrocytes in vitro, and we found that apigenin reduced markers of inflammation and cellular senescence in these cells. Collectively, our data suggest that apigenin may protect against age-related cognitive dysfunction by suppressing neuro-inflammatory processes.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"217 ","pages":"Article 111889"},"PeriodicalIF":5.3,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138440866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The skin of the naked mole-rat and its resilience against aging and cancer 裸鼹鼠的皮肤及其抗衰老和抗癌的弹性。
IF 5.3 3区 医学
Mechanisms of Ageing and Development Pub Date : 2023-11-21 DOI: 10.1016/j.mad.2023.111887
Meinhard Wlaschek , Karmveer Singh , Pallab Maity , Karin Scharffetter-Kochanek
{"title":"The skin of the naked mole-rat and its resilience against aging and cancer","authors":"Meinhard Wlaschek ,&nbsp;Karmveer Singh ,&nbsp;Pallab Maity ,&nbsp;Karin Scharffetter-Kochanek","doi":"10.1016/j.mad.2023.111887","DOIUrl":"10.1016/j.mad.2023.111887","url":null,"abstract":"<div><p>The naked mole-rat (NMR) <em>Heterocephalus glaber</em> (from the Greek/latin words ἕτερος, heteros = divergent, κεφαλή, kephalē = head and glabra = hairless) was first described by Rüppell (Fig. 1) and belongs to the Hystricognath (from the Greek words ὕστριξ, hystrix = porcupine and γνάθος, gnathos = jaw) as a suborder of rodents. NMR are characterized by the highest longevity among rodents and reveal a profound cancer resistance. Details of its skin-specific protective and resistance mechanisms against aging and carcinogenesis have so far not been adequately characterized. Recently, our knowledge of NMR skin biology was complemented and expanded by published data using state-of-the art histological and molecular techniques.</p><p>Here we review and integrate novel published data regarding skin morphology and histology of the aging NMR and the underlying mechanisms at the cellular and molecular level. We relate this data to the longevity of the NMR and its resistance to neoplastic transformation and discuss further open questions to understand its extraordinary longevity. In addition, we will address the exposome, defined as “the total of all non-genetic, endogenous and exogenous environmental influences” on the skin, respiratory tract, stomach, and intestine. Finally, we will discuss in perspective further intriguing possibilities arising from the interaction of skin with other organs.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"216 ","pages":"Article 111887"},"PeriodicalIF":5.3,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0047637423001136/pdfft?md5=e4340b9aeb1b2ca60d6dd9110479a5ba&pid=1-s2.0-S0047637423001136-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138295504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Piezo1 transforms mechanical stress into pro senescence signals and promotes osteoarthritis severity Piezo1将机械应力转化为促衰老信号,并促进骨关节炎的严重程度。
IF 5.3 3区 医学
Mechanisms of Ageing and Development Pub Date : 2023-10-13 DOI: 10.1016/j.mad.2023.111880
Yikai Liu , Zian Zhang , Jun Li , Bingying Chang , Qingbo Lin , Fengyu Wang , Wenzhe Wang , Haining Zhang
{"title":"Piezo1 transforms mechanical stress into pro senescence signals and promotes osteoarthritis severity","authors":"Yikai Liu ,&nbsp;Zian Zhang ,&nbsp;Jun Li ,&nbsp;Bingying Chang ,&nbsp;Qingbo Lin ,&nbsp;Fengyu Wang ,&nbsp;Wenzhe Wang ,&nbsp;Haining Zhang","doi":"10.1016/j.mad.2023.111880","DOIUrl":"10.1016/j.mad.2023.111880","url":null,"abstract":"<div><p><span>Osteoarthritis (OA) is a prevalent disease among elderly people and is often characterized by chronic joint pain and dysfunction. Recently, growing evidence of chondrocyte senescence in the pathogenesis of OA has been found, and targeting senescence has started to be recognized as a therapeutic approach for OA. Piezo1, a mechanosensitive Ca</span><sup>2+</sup><span> channel, has been reported to be harmful in sensing abnormal mechanical overloading and leading to chondrocyte apoptosis. However, whether Piezo1 can transform mechanical signals into senescence signals has rarely been reported. In this study, we found that severe OA cartilage expressed more Piezo1 and the senescence markers p16<span> and p21. 24 h of periodic mechanical stress induced chondrocyte senescence in vitro. In addition, we demonstrated the pivotal role of Piezo1 in OA chondrocyte senescence induced by mechanical stress. Piezo1 sensed mechanical stress and promoted chondrocyte senescence via its Ca</span></span><sup>2+</sup> channel ability. Moreover, Piezo1 promoted SASP factors production under mechanical stress, particularly in IL-6 and IL-1β. p38MAPK and NF-κB activation were two key pathways that responded to Piezo1 activation and promoted IL-6 and IL-1β production, respectively. Collectively, our study revealed a connection between abnormal mechanical stress and chondrocyte senescence, which was mediated by Piezo1.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"216 ","pages":"Article 111880"},"PeriodicalIF":5.3,"publicationDate":"2023-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41236647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The age-related characteristics in bone microarchitecture, osteoclast distribution pattern, functional and transcriptomic alterations of BMSCs in mice 小鼠骨髓间充质干细胞的骨微结构、破骨细胞分布模式、功能和转录组改变的年龄相关性特征。
IF 5.3 3区 医学
Mechanisms of Ageing and Development Pub Date : 2023-10-12 DOI: 10.1016/j.mad.2023.111877
QianKun Yang , ZhiYuan Wei , XiaoYu Wei , Jie Zhang , Yong Tang , Xiang Zhou , Pan Liu , Ce Dou , Fei Luo
{"title":"The age-related characteristics in bone microarchitecture, osteoclast distribution pattern, functional and transcriptomic alterations of BMSCs in mice","authors":"QianKun Yang ,&nbsp;ZhiYuan Wei ,&nbsp;XiaoYu Wei ,&nbsp;Jie Zhang ,&nbsp;Yong Tang ,&nbsp;Xiang Zhou ,&nbsp;Pan Liu ,&nbsp;Ce Dou ,&nbsp;Fei Luo","doi":"10.1016/j.mad.2023.111877","DOIUrl":"10.1016/j.mad.2023.111877","url":null,"abstract":"<div><p><span>Deteriorated age-related bone loss<span> is the hallmarks of skeletal aging. However, how the aging of bone marrow mesenchymal stem cells (BMSCs) and </span></span>osteoclasts<span><span> are linked to the bone microstructure degeneration is not yet very clear. In this study, the characteristics of age-related bone loss, distribution patterns of osteoclasts, functional and transcriptomic alterations of BMSCs, hub genes responsible for BMSCs senescence, were analyzed. Our study revealed an age-related declined trends in trabecular and cortical bones of femur, tibia and </span>lumbar vertebra<span><span> in mice, which was accompanied by a shift from the trabecular to cortical bones in osteoclasts. Additionally, middle-aged or aged mice exhibited remarkably reduced dynamic bone formation capacities, along with reversed osteogenic-adipogenic differentiation potentials in BMSCs. Finally, transcriptomic analysis indicated that aging-related signaling pathways were significantly activated in BMSCs from aged mice (e.g., </span>cellular senescence<span>, p53 signaling pathway, etc.). Also, weighted correlation network analysis (WGCNA) and venn diagram analysis based on our RNA-Seq data and GSE35956 dataset revealed the critical role of PTPN1 in BMSCs senescence. Targeted inhibition of PTP1B with AAV-Ptpn1-RNAi dramatically postponed age-related bone loss in middle-aged mice. Collectively, our study has uncovered the age-dependent cellular characteristics in BMSCs and osteoclasts underlying progressive bone loss with advancing age.</span></span></span></p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"216 ","pages":"Article 111877"},"PeriodicalIF":5.3,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41204697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Decreased oxidative stress response and oxidant detoxification of skin during aging 在衰老过程中降低了皮肤的氧化应激反应和氧化解毒作用。
IF 5.3 3区 医学
Mechanisms of Ageing and Development Pub Date : 2023-10-11 DOI: 10.1016/j.mad.2023.111878
Xixia Dai, Yibo Hu, Ling Jiang, Li Lei, Chuhan Fu, Songjiang Wu, Xiaolin Zhang, Lu Zhu, Fan Zhang, Jing Chen, Qinghai Zeng
{"title":"Decreased oxidative stress response and oxidant detoxification of skin during aging","authors":"Xixia Dai,&nbsp;Yibo Hu,&nbsp;Ling Jiang,&nbsp;Li Lei,&nbsp;Chuhan Fu,&nbsp;Songjiang Wu,&nbsp;Xiaolin Zhang,&nbsp;Lu Zhu,&nbsp;Fan Zhang,&nbsp;Jing Chen,&nbsp;Qinghai Zeng","doi":"10.1016/j.mad.2023.111878","DOIUrl":"10.1016/j.mad.2023.111878","url":null,"abstract":"<div><p>Oxidative stress plays an important role in the skin aging process; however, the mechanisms are not fully elucidated. Especially the changes in various types of skin cells with aging and the key oxidative stress-related genes that play a regulatory role are not clear. In this study, single-cell RNA sequencing data and microarray transcriptome data were used to explore the changes in oxidative stress response and oxidant detoxification capacity of skin cells during aging and oxidative stress-related genes potentially involved in regulating skin aging were searched. The oxidative stress response and oxidant detoxification ability were weakened in the elderly compared with those of the young. Among the different types of skin cells, keratinocytes, melanocytes, vascular endothelial cells, fibroblasts, and lymphatic endothelial cells exhibited a stronger oxidative stress response and oxidant detoxification ability, while immune cells exhibited a weaker oxidative stress response and detoxification capacity. During aging, the oxidative stress response and oxidant detoxification capacity of keratinocytes, fibroblasts, macrophages, and vascular endothelial cells were significantly weakened. Annexin A1 (ANXA1) and Apolipoprotein E (APOE) may be key oxidative stress-related genes affecting skin aging.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"216 ","pages":"Article 111878"},"PeriodicalIF":5.3,"publicationDate":"2023-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41204695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Hutchinson-Gilford progeria syndrome: Cardiovascular manifestations and treatment Hutchinson-Gilford早衰综合征:心血管表现和治疗。
IF 5.3 3区 医学
Mechanisms of Ageing and Development Pub Date : 2023-10-11 DOI: 10.1016/j.mad.2023.111879
Jing Lian , Linfang Du , Yang Li , Yue Yin , Lu Yu , Shengwei Wang , Heng Ma
{"title":"Hutchinson-Gilford progeria syndrome: Cardiovascular manifestations and treatment","authors":"Jing Lian ,&nbsp;Linfang Du ,&nbsp;Yang Li ,&nbsp;Yue Yin ,&nbsp;Lu Yu ,&nbsp;Shengwei Wang ,&nbsp;Heng Ma","doi":"10.1016/j.mad.2023.111879","DOIUrl":"10.1016/j.mad.2023.111879","url":null,"abstract":"<div><p>Hutchinson-Gilford progeria<span> syndrome (HGPS), also known as hereditary progeria syndrome, is caused by mutations in the LMNA<span> gene and the expression of progerin, which causes accelerated aging and premature death, with most patients dying of heart failure or other cardiovascular complications in their teens. HGPS patients are able to exhibit cardiovascular phenotypes similar to physiological aging, such as extensive atherosclerosis, smooth muscle cell loss, vascular lesions, and electrical and functional abnormalities of the heart. It also excludes the traditional risk causative factors of cardiovascular disease, making HGPS a new model for studying aging-related cardiovascular disease. Here, we analyzed the pathogenesis and pathophysiological characteristics of HGPS and the relationship between HGPS and cardiovascular disease, provided insight into the molecular mechanisms of cardiovascular disease pathogenesis in HGPS patients and treatment strategies for this disease. Moreover, we summarize the disease models used in HGPS studies to improve our understanding of the pathological mechanisms of cardiovascular aging in HGPS patients.</span></span></p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"216 ","pages":"Article 111879"},"PeriodicalIF":5.3,"publicationDate":"2023-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41204696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Serum levels of soluble suppression of tumorigenicity 2 (sST2) and heart-type fatty acid binding protein (H-FABP) independently predict in-hospital mortality in geriatric patients with COVID-19 血清可溶性抑瘤性2(sST2)和心脏型脂肪酸结合蛋白(H-FABP)水平独立预测老年新冠肺炎患者的住院死亡率。
IF 5.3 3区 医学
Mechanisms of Ageing and Development Pub Date : 2023-10-04 DOI: 10.1016/j.mad.2023.111876
Jacopo Sabbatinelli , Mirko Di Rosa , Angelica Giuliani , Marco Domenichelli , Anna Rita Bonfigli , Riccardo Sarzani , Antonio Cherubini , Roberto Antonicelli , Maurizio Burattini , Andrea Corsonello , Roberta Galeazzi , Lucia Babini , Marco Moretti , Antonio Domenico Procopio , Fabrizia Lattanzio , Fabiola Olivieri
{"title":"Serum levels of soluble suppression of tumorigenicity 2 (sST2) and heart-type fatty acid binding protein (H-FABP) independently predict in-hospital mortality in geriatric patients with COVID-19","authors":"Jacopo Sabbatinelli ,&nbsp;Mirko Di Rosa ,&nbsp;Angelica Giuliani ,&nbsp;Marco Domenichelli ,&nbsp;Anna Rita Bonfigli ,&nbsp;Riccardo Sarzani ,&nbsp;Antonio Cherubini ,&nbsp;Roberto Antonicelli ,&nbsp;Maurizio Burattini ,&nbsp;Andrea Corsonello ,&nbsp;Roberta Galeazzi ,&nbsp;Lucia Babini ,&nbsp;Marco Moretti ,&nbsp;Antonio Domenico Procopio ,&nbsp;Fabrizia Lattanzio ,&nbsp;Fabiola Olivieri","doi":"10.1016/j.mad.2023.111876","DOIUrl":"10.1016/j.mad.2023.111876","url":null,"abstract":"<div><p>Elevation of cardiac damage biomarkers is associated with adverse clinical outcomes and increased mortality in COVID-19 patients. This study assessed the association of admission serum levels of sST2 and H-FABP with in-hospital mortality in 191 geriatric patients (median age 86 yrs., IQR 82–91 yrs.) with COVID-19 and available measures of hs-cTnT and NT-proBNP at admission. Cox proportional hazards models were utilized to predict in-hospital mortality, considering clinical/biochemical confounders as covariates. A composite cardiac score was calculated to improve predictive accuracy. Patients deceased during their hospital stay (26%) exhibited higher levels of all biomarkers, which demonstrated good discrimination for in-hospital mortality. Addition of sST2 and H-FABP significantly improved the discriminatory power of hs-cTnT and NT-proBNP. The composite cardiac score (AUC=0.866) further enhanced the predictive accuracy. Crude and adjusted Cox regressions models revealed that both sST2 and H-FABP were independently associated with in-hospital mortality (HR for sST2 ≥129 ng/mL, 4.32 [1.48–12.59]; HR for H-FABP ≥18 ng/mL, 7.70 [2.12–28.01]). The composite cardiac score also independently correlated with in-hospital mortality (HR for 1-unit increase, 1.47 [1.14–1.90]). In older patients with COVID-19, sST2 and H-FABP demonstrated prognostic value, improving the predictive accuracy of the routinely assessed biomarkers hs-cTnT and NT-proBNP.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"216 ","pages":"Article 111876"},"PeriodicalIF":5.3,"publicationDate":"2023-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41123648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Lack of activity of the mitochondrial large-conductance calcium-regulated potassium channels in senescent vascular smooth muscle cells. 衰老血管平滑肌细胞线粒体大电导钙调节钾通道缺乏活性。
IF 5.3 3区 医学
Mechanisms of Ageing and Development Pub Date : 2023-10-01 DOI: 10.1016/j.mad.2023.111871
Agata Głuchowska , Barbara Kalenik , Bogusz Kulawiak , Antoni Wrzosek , Adam Szewczyk , Piotr Bednarczyk , Grażyna Mosieniak
{"title":"Lack of activity of the mitochondrial large-conductance calcium-regulated potassium channels in senescent vascular smooth muscle cells.","authors":"Agata Głuchowska ,&nbsp;Barbara Kalenik ,&nbsp;Bogusz Kulawiak ,&nbsp;Antoni Wrzosek ,&nbsp;Adam Szewczyk ,&nbsp;Piotr Bednarczyk ,&nbsp;Grażyna Mosieniak","doi":"10.1016/j.mad.2023.111871","DOIUrl":"10.1016/j.mad.2023.111871","url":null,"abstract":"<div><p>A limited number of studies have shown functional changes in mitochondrial ion channels in aging and senescent cells. We have identified, for the first time, mitochondrial large-conductance calcium-regulated potassium channels in human smooth muscle mitochondria. This channel, with a conductance of 273 pS, was regulated by calcium ions and membrane potential. Additionally, it was activated by the potassium channel opener NS11021 and blocked by paxilline. Importantly, we have shown that senescence of these cells induced by hydrogen peroxide treatment leads to the disappearance of potassium channel protein levels and channel activity measured by the single channel patch-clamp technique. Our data suggest that disturbances in the expression of mitochondrial large conductance calcium-regulated potassium channels may be hallmarks of cellular senescence and contribute to the misregulation of mitochondrial function in senescent cells.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"215 ","pages":"Article 111871"},"PeriodicalIF":5.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10192025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Assessment and risk prediction of frailty using texture-based muscle ultrasound image analysis and machine learning techniques 使用基于纹理的肌肉超声图像分析和机器学习技术评估和风险预测虚弱。
IF 5.3 3区 医学
Mechanisms of Ageing and Development Pub Date : 2023-10-01 DOI: 10.1016/j.mad.2023.111860
Rebeca Mirón-Mombiela , Silvia Ruiz-España , David Moratal , Consuelo Borrás
{"title":"Assessment and risk prediction of frailty using texture-based muscle ultrasound image analysis and machine learning techniques","authors":"Rebeca Mirón-Mombiela ,&nbsp;Silvia Ruiz-España ,&nbsp;David Moratal ,&nbsp;Consuelo Borrás","doi":"10.1016/j.mad.2023.111860","DOIUrl":"10.1016/j.mad.2023.111860","url":null,"abstract":"<div><p>The purpose of this study was to evaluate texture-based muscle ultrasound image analysis for the assessment and risk prediction of frailty phenotype. This retrospective study of prospectively acquired data included 101 participants who underwent ultrasound scanning of the anterior thigh. Participants were subdivided according to frailty phenotype and were followed up for two years. Primary and secondary outcome measures were death and comorbidity, respectively. Forty-three texture features were computed from the <em>rectus femoris</em> and the <em>vastus intermedius</em> muscles using statistical methods. Model performance was evaluated by computing the area under the receiver operating characteristic curve (AUC) while outcome prediction was evaluated using regression analysis. Models developed achieved a moderate to good AUC (0.67 ≤ AUC ≤ 0.79) for categorizing frailty. The stepwise multiple logistic regression analysis demonstrated that they correctly classified 70–87% of the cases. The models were associated with increased comorbidity (0.01 ≤ <em>p</em> ≤ 0.18) and were predictive of death for pre-frail and frail participants (0.001 ≤ <em>p</em> ≤ 0.016). In conclusion, texture analysis can be useful to identify frailty and assess risk prediction (i.e. mortality) using texture features extracted from muscle ultrasound images in combination with a machine learning approach.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"215 ","pages":"Article 111860"},"PeriodicalIF":5.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10242364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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