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

Age-dependent energy metabolism and transcriptome changes in urine-derived stem cells 尿液衍生干细胞随年龄变化的能量代谢和转录组变化

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-01-22 DOI: 10.1016/j.mad.2024.111912

Elisabete Ferreiro , Mariana Monteiro , Francisco Pereira , Cristina Barroso , Conceição Egas , Paula Macedo , Jorge Valero , Vilma A. Sardão , Paulo J. Oliveira

{"title":"Age-dependent energy metabolism and transcriptome changes in urine-derived stem cells","authors":"Elisabete Ferreiro , Mariana Monteiro , Francisco Pereira , Cristina Barroso , Conceição Egas , Paula Macedo , Jorge Valero , Vilma A. Sardão , Paulo J. Oliveira","doi":"10.1016/j.mad.2024.111912","DOIUrl":"10.1016/j.mad.2024.111912","url":null,"abstract":"<div><p>The global population over 60 years old is projected to reach 1.5 billion by 2050. Understanding age-related disorders and gender-specificities is crucial for a healthy aging. Reliable age-related biomarkers are needed, preferentially obtained through non-invasive methods. Urine-derived stem cells (UDSCs) can be easily obtained, although a detailed bioenergetic characterization, according to the donor aging, remain unexplored. UDSCs were isolated from young and elderly adult women (22–35 and 70–94 years old, respectively). Surprisingly, UDSCs from elderly subjects exhibited significantly higher maximal oxygen consumption and bioenergetic health index than those from younger individuals, evaluated through oxygen consumption rate. Exploratory data analysis methods were applied to engineer a minimal subset of features for the classification and stratification of UDSCs. Additionally, RNAseq of UDSCs was performed to identify age-related transcriptional changes. Transcriptional analysis revealed downregulation of genes related to glucuronidation and estrogen metabolism, and upregulation of inflammation-related genes in UDSCs from elderly individuals. This study demonstrates unexpected differences in the UDSCs’ OCR between young and elderly individuals, revealing improved bioenergetics in concurrent with an aged-like transcriptome signature. UDSCs offer a non-invasive model for studying age-related changes, holding promise for aging research and therapeutic studies.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"218 ","pages":"Article 111912"},"PeriodicalIF":5.3,"publicationDate":"2024-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0047637424000125/pdfft?md5=27c318b23e96ebea1cf3790fc436fbb9&pid=1-s2.0-S0047637424000125-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139523499","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

Calcium transferring from ER to mitochondria via miR-129/ITPR2 axis controls cellular senescence in vitro and in vivo 钙通过 miR-129/ITPR2 轴从 ER 转移到线粒体，控制体外和体内的细胞衰老

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-01-11 DOI: 10.1016/j.mad.2024.111902

Yue Gao , Lei Xu , Yaru Li , Dandan Qi , Chaofan Wang , Changjiao Luan , Shihui Zheng , Qiu Du , Weili Liu , Guotao Lu , Weijuan Gong , Xingjie Ma

{"title":"Calcium transferring from ER to mitochondria via miR-129/ITPR2 axis controls cellular senescence in vitro and in vivo","authors":"Yue Gao , Lei Xu , Yaru Li , Dandan Qi , Chaofan Wang , Changjiao Luan , Shihui Zheng , Qiu Du , Weili Liu , Guotao Lu , Weijuan Gong , Xingjie Ma","doi":"10.1016/j.mad.2024.111902","DOIUrl":"10.1016/j.mad.2024.111902","url":null,"abstract":"<div><p><span><span>Senescent cells are known to be accumulated in aged organisms. Although the two main characteristics, cell cycle arrest (for dividing cells) and secretion of senescence-associated secretory phenotype (SASP) factors, have been well described, the lack of sufficient senescent markers and incomplete understanding of mechanisms have limited the progress of the anti-senescence field. Calcium transferred from the </span>endoplasmic reticulum<span> (ER) via inositol 1, 4, 5-trisphosphate receptor type 2 (ITPR2) to mitochondria has emerged as a key player during cellular senescence and aging. However, the internal regulatory mechanisms, particularly those of endogenous molecules, remain only partially understood. Here we identified miRNA-129 (miR-129) as a direct repressor of </span></span><em>ITPR2</em><span><span><span>. Interestingly, miR-129 controlled a cascade of intracellular calcium signaling, </span>mitochondrial membrane potential (MMP), </span>reactive oxygen species<span><span> (ROS), DNA damage, and consequently cellular senescence through ITPR2 and mitochondrial calcium uniporter<span> (MCU). In addition, miR-129 was repressed in different senescence models and delayed bleomycin-induced cellular senescence. Importantly, intraperitoneal injection of miR-129 partly postponed bleomycin-accelerated lung aging and natural aging markers as well as reduced </span></span>immunosenescence markers in mice. Altogether, these findings demonstrated that miR-129 regulated cellular senescence and aging markers via intracellular calcium signaling by directly targeting </span></span><em>ITPR2.</em></p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"218 ","pages":"Article 111902"},"PeriodicalIF":5.3,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139420706","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

Novel 18-norspirostane steroidal saponins: Extending lifespan and mitigating neurodegeneration through promotion of mitophagy and mitochondrial biogenesis in Caenorhabditis elegans 新型 18-Norspirostane 类固醇皂甙：通过促进线粒体吞噬和线粒体生物生成延长秀丽隐杆线虫的寿命并缓解神经退行性变

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-01-10 DOI: 10.1016/j.mad.2024.111901

An-Guo Wu , Yuan-Yuan Yong , Chang-Long He , Ya-Ping Li , Xing-Yue Zhou , Lu Yu , Qi Chen , Cai Lan , Jian Liu , Chong-Lin Yu , Da-Lian Qin , Jian-Ming Wu , Xiao-Gang Zhou

{"title":"Novel 18-norspirostane steroidal saponins: Extending lifespan and mitigating neurodegeneration through promotion of mitophagy and mitochondrial biogenesis in Caenorhabditis elegans","authors":"An-Guo Wu , Yuan-Yuan Yong , Chang-Long He , Ya-Ping Li , Xing-Yue Zhou , Lu Yu , Qi Chen , Cai Lan , Jian Liu , Chong-Lin Yu , Da-Lian Qin , Jian-Ming Wu , Xiao-Gang Zhou","doi":"10.1016/j.mad.2024.111901","DOIUrl":"10.1016/j.mad.2024.111901","url":null,"abstract":"<div><p><span>Pharmacological strategies to delay aging and combat age-related diseases are increasingly promising. This study explores the anti-aging and therapeutic effects of two novel 18-norspirostane steroidal saponins from </span><em>Trillium tschonoskii</em> Maxim, namely deoxytrillenoside CA (DTCA) and epitrillenoside CA (ETCA), using <span><em>Caenorhabditis elegans</em></span> (<em>C. elegans</em><span><span><span>). Both DTCA and ETCA significantly extended the lifespan of wild-type N2 worms and improved various age-related phenotypes, including muscle health, motility, pumping rate, and lipofuscin accumulation. Furthermore, these compounds exhibited notable alleviation of pathology associated with </span>Parkinson's disease (PD) and </span>Huntington's disease (HD), such as the reduction of α-synuclein and poly40 aggregates, improvement in motor deficits, and mitigation of neuronal damage. Meanwhile, DTCA and ETCA improved the lifespan and healthspan of PD- and HD-like </span><em>C. elegans</em> models. Additionally, DTCA and ETCA enhanced the resilience of <em>C. elegans</em><span><span> against heat and oxidative stress<span> challenges. Mechanistic studies elucidated that DTCA and ETCA induced mitophagy and promoted </span></span>mitochondrial biogenesis in </span><em>C. elegans</em><span>, while genetic mutations or RNAi knockdown affecting mitophagy and mitochondrial biogenesis effectively eliminated their capacity to extend lifespan and reduce pathological protein aggregates. Together, these compelling findings highlight the potential of DTCA and ETCA as promising therapeutic interventions for delaying aging and preventing age-related diseases.</span></p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"218 ","pages":"Article 111901"},"PeriodicalIF":5.3,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139431959","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

Moderate dietary restriction delays the onset of age-associated sarcopenia in Caenorhabditis elegans due to reduced myosin UNC-54 degradation 由于肌球蛋白 UNC-54 降解减少，适度限制饮食可延缓草履虫年龄相关性肌肉疏松症的发生。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2023-12-30 DOI: 10.1016/j.mad.2023.111900

Sobha Tumbapo , Adam Strudwick , Jana J. Stastna , Simon C. Harvey , Marieke J. Bloemink

{"title":"Moderate dietary restriction delays the onset of age-associated sarcopenia in Caenorhabditis elegans due to reduced myosin UNC-54 degradation","authors":"Sobha Tumbapo , Adam Strudwick , Jana J. Stastna , Simon C. Harvey , Marieke J. Bloemink","doi":"10.1016/j.mad.2023.111900","DOIUrl":"10.1016/j.mad.2023.111900","url":null,"abstract":"<div><p>Sarcopenia, a gradual decrease in skeletal muscle mass and strength, is a major component of frailty in the elderly, with age, (lack of) exercise and diet found to be the major risk factors. The nematode <span><em>Caenorhabditis elegans</em></span> is an important model of sarcopenia. Although many studies describe loss of muscle function in ageing <em>C. elegans</em><span>, surprisingly few report on the loss of muscle mass. Here, in order to quantify loss of muscle mass under various dietary restriction (DR) conditions, we used an internal GFP standard to determine levels of the major body wall muscle myosin (UNC-54) in transgenic </span><em>unc-54::gfp</em> worms over their lifespan. Myosin density linearly increased during the first week of adulthood and there was no significant effect of DR. In contrast, an exponential decrease in myosin density was seen during the second week of adulthood, with reduced rates of myosin loss for mild and medium DR compared to control. UNC-54 turnover rates, previously determined using pulse-labelling methods, correspond well with the t<sub>1/2</sub> value found here for UNC-54-GFP using fluorescence (control t<sub>1/2</sub><span> = 12.0 days), independently validating our approach. These data indicate that sarcopenia is delayed in worms under mild and medium DR due to a reduced rate of myosin UNC-54 degradation, thereby maintaining protein homeostasis.</span></p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"217 ","pages":"Article 111900"},"PeriodicalIF":5.3,"publicationDate":"2023-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139074480","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

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}

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