Mechanisms of Ageing and Development最新文献_第10页

Sleep disorders and Alzheimer’s disease pathophysiology: The role of the Glymphatic System. A scoping review 睡眠障碍与阿尔茨海默病病理生理学：淋巴系统的作用。范围界定综述。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2023-12-30 DOI: 10.1016/j.mad.2023.111899

Kyriaki Astara , Alexandros Tsimpolis , Konstantinos Kalafatakis , George D. Vavougios , Georgia Xiromerisiou , Efthimios Dardiotis , Nikos G. Christodoulou , Myrto T. Samara , Andreas S. Lappas

{"title":"Sleep disorders and Alzheimer’s disease pathophysiology: The role of the Glymphatic System. A scoping review","authors":"Kyriaki Astara , Alexandros Tsimpolis , Konstantinos Kalafatakis , George D. Vavougios , Georgia Xiromerisiou , Efthimios Dardiotis , Nikos G. Christodoulou , Myrto T. Samara , Andreas S. Lappas","doi":"10.1016/j.mad.2023.111899","DOIUrl":"10.1016/j.mad.2023.111899","url":null,"abstract":"<div><h3>Background</h3><p>Alzheimer’s disease (AD) is highly intertwined with sleep disturbances throughout its whole natural history. Sleep consists of a major compound of the functionality of the glymphatic system, as the synchronized slow-wave activity during NREM facilitates cerebrospinal and interstitial long-distance mixing. Objective: The present study undertakes a scoping review of research on the involvement of the glymphatic system in AD-related sleep disturbances. Design: we searched Medline, Embase, PsychInfo and HEAL-link databases, without limitations on date and language, along with reference lists of relevant reviews and all included studies. We included in vivo, in vitro and post-mortem studies examining glymphatic implications of sleep disturbances in human populations with AD spectrum pathology. A thematic synthesis of evidence based on the extracted content was applied and presented in a narrative way. Results: In total, 70 original research articles were included and were grouped as following: a) Protein aggregation and toxicity, after sleep deprivation, along with its effects on sleep architecture, b) Glymphatic Sequalae in SDB, yielding potential glymphatic markers c) Circadian Dysregulation, d) Possible Interventions. Conclusions: this review sought to provide insight into the role of sleep disturbances in AD pathogenesis, in the context of the glymphatic disruption</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"217 ","pages":"Article 111899"},"PeriodicalIF":5.3,"publicationDate":"2023-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0047637423001252/pdfft?md5=0680327d3e19246259eeecdff1a7a276&pid=1-s2.0-S0047637423001252-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139074481","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

A feasibility study of the combination of intranasal insulin with oral semaglutide for cognition in older adults with metabolic syndrome at high dementia risk- Study rationale and design 鼻内胰岛素与口服塞马鲁肽联合治疗老年痴呆症高危代谢综合征患者认知能力的可行性研究--研究原理与设计

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2023-12-29 DOI: 10.1016/j.mad.2023.111898

Tal Davidy , Iscka Yore , Tali Cukierman-Yaffe , Ramit Ravona-Springer , Abigail Livny , Orit H. Lesman-Segev , Yossi Azuri , Owen Carmichael , Dimitrios Kapogiannis , Henrik Zetterberg , HungMo Lin , Mary Sano , Michal Schnaider Beeri

{"title":"A feasibility study of the combination of intranasal insulin with oral semaglutide for cognition in older adults with metabolic syndrome at high dementia risk- Study rationale and design","authors":"Tal Davidy , Iscka Yore , Tali Cukierman-Yaffe , Ramit Ravona-Springer , Abigail Livny , Orit H. Lesman-Segev , Yossi Azuri , Owen Carmichael , Dimitrios Kapogiannis , Henrik Zetterberg , HungMo Lin , Mary Sano , Michal Schnaider Beeri","doi":"10.1016/j.mad.2023.111898","DOIUrl":"10.1016/j.mad.2023.111898","url":null,"abstract":"<div><h3>Introduction</h3><p>We present the rationale and design of a double-blind placebo-controlled feasibility trial combining intranasal insulin (INI) with semaglutide<span><span>, a GLP-1 receptor agonist<span>, to improve cognition in older adults with metabolic syndrome (MetS) and mild cognitive impairment (MCI). Since both INI and </span></span>dulaglutide<span> have beneficial effects on the cerebrovascular disease (CVD), we anticipate that improved CVD will underlie the hypothesized cognitive benefits.</span></span></p></div><div><h3>Methods</h3><p>This 12-months trial will include 80 older adults aged > 60 with MetS and MCI, randomized to 4 groups: INI/oral semaglutide, intranasal placebo/oral semaglutide, INI/oral placebo<span>, and intranasal placebo/oral placebo. Feasibility of combining INI with semaglutide will be tested by examining the ease of use of INI (20IU, twice/day) with semaglutide (14 once daily), adherence, and safety profile are the efficacy of combination therapy on global cognition and neurobiological markers: cerebral blood flow, cerebral glucose utilization<span>, white matter hyperintensities, Alzheimer’s related blood biomarkers and expression of insulin signaling proteins measured in brain-derived exosomes. Efficacy will be assessed for the intent-to-treat sample.</span></span></p></div><div><h3>Discussion</h3><p>This feasibility study is anticipated to provide the basis for a multi-center large-scale randomized clinical trial (RCT) of the cognitive benefits of the combination of INI with semaglutide in individuals enriched for CVD and at high dementia risk.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"218 ","pages":"Article 111898"},"PeriodicalIF":5.3,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139068711","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 cGAS-STING signaling pathway is modulated by urolithin A cGAS-STING 信号通路受卵磷脂 A 调节

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2023-12-16 DOI: 10.1016/j.mad.2023.111897

H.B. Madsen , J-H. Park , X. Chu , Y. Hou , Z. Li , L.J. Rasmussen , D.L. Croteau , V.A. Bohr , M. Akbari

{"title":"The cGAS-STING signaling pathway is modulated by urolithin A","authors":"H.B. Madsen , J-H. Park , X. Chu , Y. Hou , Z. Li , L.J. Rasmussen , D.L. Croteau , V.A. Bohr , M. Akbari","doi":"10.1016/j.mad.2023.111897","DOIUrl":"10.1016/j.mad.2023.111897","url":null,"abstract":"<div><p>During aging, general cellular processes, including autophagic clearance and immunological responses become compromised; therefore, identifying compounds that target these cellular processes is an important approach to improve our health span. The innate immune cGAS-STING pathway has emerged as an important signaling system in the organismal defense against viral and bacterial infections, inflammatory responses to cellular damage, regulation of autophagy, and tumor immunosurveillance. These key functions of the cGAS-STING pathway make it an attractive target for pharmacological intervention in disease treatments and in controlling inflammation and immunity. Here, we show that urolithin A (UA), an ellagic acid metabolite, exerts a profound effect on the expression of STING and enhances cGAS-STING activation and cytosolic DNA clearance in human cell lines. Animal laboratory models and limited human trials have reported no obvious adverse effects of UA administration. Thus, the use of UA alone or in combination with other pharmacological compounds may present a potential therapeutic approach in the treatment of human diseases that involves aberrant activation of the cGAS-STING pathway or accumulation of cytosolic DNA and this warrants further investigation in relevant transgenic animal models.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"217 ","pages":"Article 111897"},"PeriodicalIF":5.3,"publicationDate":"2023-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0047637423001239/pdfft?md5=586765e6a043972bd52f6541d7f87ef0&pid=1-s2.0-S0047637423001239-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138684650","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

Relation of the kynurenine pathway with normal age: A systematic review 犬尿氨酸通路与正常年龄关系的系统综述。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2023-12-05 DOI: 10.1016/j.mad.2023.111890

Lieke Bakker , Kyonghwan Choe , Simone J.P.M. Eussen , Inez H.G.B. Ramakers , Daniel L.A. van den Hove , Gunter Kenis , Bart P.F. Rutten , Frans R.J. Verhey , Sebastian Köhler

{"title":"Relation of the kynurenine pathway with normal age: A systematic review","authors":"Lieke Bakker , Kyonghwan Choe , Simone J.P.M. Eussen , Inez H.G.B. Ramakers , Daniel L.A. van den Hove , Gunter Kenis , Bart P.F. Rutten , Frans R.J. Verhey , Sebastian Köhler","doi":"10.1016/j.mad.2023.111890","DOIUrl":"10.1016/j.mad.2023.111890","url":null,"abstract":"<div><h3>Background</h3><p>The kynurenine pathway (KP) is gaining more attention as a common pathway involved in age-related conditions. However, which changes in the KP occur due to normal ageing is still largely unclear. The aim of this systematic review was to summarize the available evidence for associations of KP metabolites with age.</p></div><div><h3>Methods</h3><p>We used an broad search strategy and included studies up to October 2023.</p></div><div><h3>Results</h3><p>Out of 8795 hits, 55 studies were eligible for the systematic review. These studies suggest that blood levels of tryptophan decrease with age, while blood and cerebrospinal fluid levels of kynurenine and its ratio with tryptophan increase. Studies investigating associations between cerebrospinal fluid and blood levels of kynurenic acid and quinolinic acid with age reported either positive or non-significant findings. However, there is a large heterogeneity across studies. Additionally, most studies were cross-sectional, and only few studies investigated associations with other downstream kynurenines.</p></div><div><h3>Conclusions</h3><p>This systematic review suggests that levels of kynurenines are positively associated with age. Larger and prospective studies are needed that also investigate a more comprehensive panel of KP metabolites and changes during the life-course.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"217 ","pages":"Article 111890"},"PeriodicalIF":5.3,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0047637423001161/pdfft?md5=c1859406aaa5400080ec3acd87b31d2e&pid=1-s2.0-S0047637423001161-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138498822","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

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 , 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 , Zachary S. Clayton , Devin Wahl , David A. Hutton , Cali M. McEntee , Douglas R. Seals , 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 , Karmveer Singh , Pallab Maity , 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 , Zian Zhang , Jun Li , Bingying Chang , Qingbo Lin , Fengyu Wang , Wenzhe Wang , 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

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 , ZhiYuan Wei , XiaoYu Wei , Jie Zhang , Yong Tang , Xiang Zhou , Pan Liu , Ce Dou , 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, Yibo Hu, Ling Jiang, Li Lei, Chuhan Fu, Songjiang Wu, Xiaolin Zhang, Lu Zhu, Fan Zhang, Jing Chen, 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