Mechanisms of Ageing and Development最新文献_第7页

Common and distinct metabolomic markers related to immune aging in Western European and East African populations 西欧和东非人群中与免疫衰老有关的共同和独特代谢组标记物

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-02-14 DOI: 10.1016/j.mad.2024.111916

Ozlem Bulut , Godfrey S. Temba , Valerie A.C.M. Koeken , Simone J.C.F.M. Moorlag , L. Charlotte J. de Bree , Vera P. Mourits , Vesla I. Kullaya , Martin Jaeger , Cancan Qi , Niels P. Riksen , Jorge Domínguez-Andrés , Cheng-Jian Xu , Leo A.B. Joosten , Yang Li , Quirijn de Mast , Mihai G. Netea

{"title":"Common and distinct metabolomic markers related to immune aging in Western European and East African populations","authors":"Ozlem Bulut , Godfrey S. Temba , Valerie A.C.M. Koeken , Simone J.C.F.M. Moorlag , L. Charlotte J. de Bree , Vera P. Mourits , Vesla I. Kullaya , Martin Jaeger , Cancan Qi , Niels P. Riksen , Jorge Domínguez-Andrés , Cheng-Jian Xu , Leo A.B. Joosten , Yang Li , Quirijn de Mast , Mihai G. Netea","doi":"10.1016/j.mad.2024.111916","DOIUrl":"https://doi.org/10.1016/j.mad.2024.111916","url":null,"abstract":"<div><p>In old age, impaired immunity causes high susceptibility to infections and cancer, higher morbidity and mortality, and poorer vaccination efficiency. Many factors, such as genetics, diet, and lifestyle, impact aging. This study aimed to investigate how immune responses change with age in healthy Dutch and Tanzanian individuals and identify common metabolites associated with an aged immune profile. We performed untargeted metabolomics from plasma to identify age-associated metabolites, and we correlated their concentrations with <em>ex-vivo</em> cytokine production by immune cells, DNA methylation-based epigenetic aging, and telomere length. Innate immune responses were impacted differently by age in Dutch and Tanzanian cohorts. Age-related decline in steroid hormone precursors common in both populations was associated with higher systemic inflammation and lower cytokine responses. Hippurate and 2-phenylacetamide, commonly more abundant in older individuals, were negatively correlated with cytokine responses and telomere length and positively correlated with epigenetic aging. Lastly, we identified several metabolites that might contribute to the stronger decline in innate immunity with age in Tanzanians. The shared metabolomic signatures of the two cohorts suggest common mechanisms of immune aging, revealing metabolites with potential contributions. These findings also reflect genetic or environmental effects on circulating metabolites that modulate immune responses.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"218 ","pages":"Article 111916"},"PeriodicalIF":5.3,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0047637424000162/pdfft?md5=40a7284951bc886f679842b24682f73b&pid=1-s2.0-S0047637424000162-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139744103","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

Long-COVID-19 autonomic dysfunction: An integrated view in the framework of inflammaging Long-COVID-19 自主神经功能障碍：炎症框架下的综合观点。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-02-13 DOI: 10.1016/j.mad.2024.111915

Sergio Giunta , Chiara Giordani , Maria De Luca , Fabiola Olivieri

{"title":"Long-COVID-19 autonomic dysfunction: An integrated view in the framework of inflammaging","authors":"Sergio Giunta , Chiara Giordani , Maria De Luca , Fabiola Olivieri","doi":"10.1016/j.mad.2024.111915","DOIUrl":"10.1016/j.mad.2024.111915","url":null,"abstract":"<div><p>The recently identified syndrome known as Long COVID (LC) is characterized by a constellation of debilitating conditions that impair both physical and cognitive functions, thus reducing the quality of life and increasing the risk of developing the most common age-related diseases. These conditions are linked to the presence of symptoms of autonomic dysfunction, in association with low cortisol levels, suggestive of reduced hypothalamic-pituitary-adrenal (HPA) axis activity, and with increased pro-inflammatory condition. Alterations of dopamine and serotonin neurotransmitter levels were also recently observed in LC. Interestingly, at least some of the proposed mechanisms of LC development overlap with mechanisms of Autonomic Nervous System (ANS) imbalance, previously detailed in the framework of the aging process. ANS imbalance is characterized by a proinflammatory sympathetic overdrive, and a concomitant decreased anti-inflammatory vagal parasympathetic activity, associated with reduced anti-inflammatory effects of the HPA axis and cholinergic anti-inflammatory pathway (CAP). These neuro-immune-endocrine system imbalanced activities fuel the vicious circle of chronic inflammation, <em>i.e.</em> inflammaging. Here, we refine our original hypothesis that ANS dysfunction fuels inflammaging and propose that biomarkers of ANS imbalance could also be considered biomarkers of inflammaging, recognized as the main risk factor for developing age-related diseases and the sequelae of viral infections, <em>i.e.</em> LC.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"218 ","pages":"Article 111915"},"PeriodicalIF":5.3,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139735496","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

WDR23 mediates NRF2 proteostasis and cytoprotective capacity in the hippocampus WDR23 在海马中介导 NRF2 蛋白稳态和细胞保护能力

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-02-01 DOI: 10.1016/j.mad.2024.111914

Jiahui Liu, Chatrawee Duangjan , Ronald W. Irwin , Sean P. Curran

引用次数: 0

The close relationship between oocyte aging and telomere shortening, and possible interventions for telomere protection 卵母细胞老化与端粒缩短的密切关系，以及保护端粒的可能干预措施

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-02-01 DOI: 10.1016/j.mad.2024.111913

Saffet Ozturk

引用次数: 0

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