Mechanisms of Ageing and Development最新文献_第4页

Navigating oligodendrocyte precursor cell aging in brain health 导航大脑健康中的少突胶质前体细胞老化。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-06-29 DOI: 10.1016/j.mad.2024.111959

Freddy Leenders , Lisa Koole , Helena Slaets , Assia Tiane , Daniel van den Hove , Tim Vanmierlo

{"title":"Navigating oligodendrocyte precursor cell aging in brain health","authors":"Freddy Leenders , Lisa Koole , Helena Slaets , Assia Tiane , Daniel van den Hove , Tim Vanmierlo","doi":"10.1016/j.mad.2024.111959","DOIUrl":"10.1016/j.mad.2024.111959","url":null,"abstract":"<div><p>Oligodendrocyte precursor cells (OPCs) comprise 5–8 % of the adult glial cell population and stand out as the most proliferative cell type in the central nervous system (CNS). OPCs are responsible for generating oligodendrocytes (OLs), the myelinating cells of the CNS. However, OPC functions decline as we age, resulting in impaired differentiation and inadequate remyelination. This review explores the cellular and molecular changes associated with OPC aging, and their impact on OPC differentiation and functionality. Furthermore, it examines the impact of OPC aging within the context of multiple sclerosis and Alzheimer’s disease, both neurodegenerative conditions wherein aged OPCs exacerbate disease progression by impeding remyelination. Moreover, various pharmacological interventions targeting pathways related to senescence and differentiation are discussed as potential strategies to rejuvenate aged OPCs. Enhancing our understanding of OPC aging mechanisms holds promise for developing new therapies to improve remyelination and repair in age-related neurodegenerative disorders.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"220 ","pages":"Article 111959"},"PeriodicalIF":5.3,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0047637424000599/pdfft?md5=8f6ec31b977414b6df0f94db28131ae6&pid=1-s2.0-S0047637424000599-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476933","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

Lifestyle factors and metabolomic aging biomarkers: Meta-analysis of cross-sectional and longitudinal associations in three prospective cohorts 生活方式因素与代谢组衰老生物标志物：三个前瞻性队列中横截面和纵向关联的元分析。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-06-29 DOI: 10.1016/j.mad.2024.111958

L.M. Kuiper , A.P. Smit , D. Bizzarri , E.B. van den Akker , M.J.T. Reinders , M. Ghanbari , J.G.J. van Rooij , T. Voortman , F. Rivadeneira , M.E.T. Dollé , G.C.M. Herber , M.L. Rietman , H.S.J. Picavet , J.B.J. van Meurs , W.M.M. Verschuren

{"title":"Lifestyle factors and metabolomic aging biomarkers: Meta-analysis of cross-sectional and longitudinal associations in three prospective cohorts","authors":"L.M. Kuiper , A.P. Smit , D. Bizzarri , E.B. van den Akker , M.J.T. Reinders , M. Ghanbari , J.G.J. van Rooij , T. Voortman , F. Rivadeneira , M.E.T. Dollé , G.C.M. Herber , M.L. Rietman , H.S.J. Picavet , J.B.J. van Meurs , W.M.M. Verschuren","doi":"10.1016/j.mad.2024.111958","DOIUrl":"10.1016/j.mad.2024.111958","url":null,"abstract":"<div><p>Biological age uses biophysiological information to capture a person’s age-related risk of adverse outcomes. MetaboAge and MetaboHealth are metabolomics-based biomarkers of biological age trained on chronological age and mortality risk, respectively. Lifestyle factors contribute to the extent chronological and biological age differ. The association of lifestyle factors with MetaboAge and MetaboHealth, potential sex differences in these associations, and MetaboAge’s and MetaboHealth’s sensitivity to lifestyle changes have not been studied yet.</p><p>Linear regression analyses and mixed-effect models were used to examine the cross-sectional and longitudinal associations of scaled lifestyle factors with scaled MetaboAge and MetaboHealth in 24,332 middle-aged participants from the Doetinchem Cohort Study, Rotterdam Study, and UK Biobank. Random-effect meta-analyses were performed across cohorts. Repeated metabolomics measurements had a ten-year interval in the Doetinchem Cohort Study and a five-year interval in the UK Biobank.</p><p>In the first study incorporating longitudinal information on MetaboAge and MetaboHealth, we demonstrate associations between current smoking, sleeping ≥8 hours/day, higher BMI, and larger waist circumference were associated with higher MetaboHealth, the latter two also with higher MetaboAge. Furthermore, adhering to the dietary and physical activity guidelines were inversely associated with MetaboHealth. Lastly, we observed sex differences in the associations between alcohol use and MetaboHealth.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"220 ","pages":"Article 111958"},"PeriodicalIF":5.3,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476932","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

Quercetin induces senolysis of doxorubicin-induced senescent fibroblasts by reducing autophagy, preventing their pro-tumour effect on osteosarcoma cells 槲皮素通过减少自噬诱导多柔比星诱导的衰老成纤维细胞发生衰老，防止其对骨肉瘤细胞产生促瘤效应

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-06-21 DOI: 10.1016/j.mad.2024.111957

Elisa Bientinesi, Sara Ristori, Matteo Lulli, Daniela Monti

{"title":"Quercetin induces senolysis of doxorubicin-induced senescent fibroblasts by reducing autophagy, preventing their pro-tumour effect on osteosarcoma cells","authors":"Elisa Bientinesi, Sara Ristori, Matteo Lulli, Daniela Monti","doi":"10.1016/j.mad.2024.111957","DOIUrl":"10.1016/j.mad.2024.111957","url":null,"abstract":"<div><p>Cellular senescence contributes to ageing and age-related diseases, and multiple therapeutic strategies are being developed to counteract it. Senolytic drugs are being tested in clinical trials to eliminate senescent cells selectively, but their effects and mechanisms are still unclear. Several studies reveal that the upregulation of senescence-associated secretory phenotype (SASP) factors in senescent cells is accompanied by increased autophagic activity to counteract the endoplasmic reticulum (ER) stress. Our study shows that Doxo-induced senescent fibroblasts yield several SASP factors and exhibit increased autophagy. Interestingly, Quercetin, a bioactive flavonoid, reduces autophagy, increases ER stress, and partially triggers senescent fibroblast death. Given the role of senescent cells in cancer progression, we tested the effect of conditioned media from untreated and quercetin-treated senescent fibroblasts on osteosarcoma cells to determine whether senolytic treatment affected tumour cell behaviour. We report that the partial senescent fibroblast clearance, achieved by quercetin, reduced osteosarcoma cell invasiveness, curbing the pro-tumour effects of senescent cells. The reduction of cell autophagic activity and increased ER stress, an undescribed effect of quercetin, emerges as a new vulnerability of Doxo-induced senescent fibroblasts and may provide a potential therapeutic target for cancer treatment, suggesting novel drug combinations as a promising strategy against the tumour.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"220 ","pages":"Article 111957"},"PeriodicalIF":5.3,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0047637424000575/pdfft?md5=73580d4a674eba5a0fc777fa2e17c7bb&pid=1-s2.0-S0047637424000575-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443032","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

Exploring the interplay between stress mediators and skin microbiota in shaping age-related hallmarks: A review 探索压力介质和皮肤微位点在形成与年龄有关的特征方面的相互作用：综述。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-06-19 DOI: 10.1016/j.mad.2024.111956

Marco Duarte , Sílvia Santos Pedrosa , P. Raaj Khusial , Ana Raquel Madureira

{"title":"Exploring the interplay between stress mediators and skin microbiota in shaping age-related hallmarks: A review","authors":"Marco Duarte , Sílvia Santos Pedrosa , P. Raaj Khusial , Ana Raquel Madureira","doi":"10.1016/j.mad.2024.111956","DOIUrl":"10.1016/j.mad.2024.111956","url":null,"abstract":"<div><p>Psychological stress is a major contributing factor to several health problems (e.g., depression, cardiovascular disease). Around 35 % of the world’s population suffers from it, including younger generations. Physiologically, stress manifests through neuroendocrine pathways (Hypothalamic-Pituitary-Adrenal (HPA) axis and Sympathetic-Adrenal-Medullary (SAM) system) which culminate in the production of stress mediators like cortisol, epinephrine and norepinephrine. Stress and its mediators have been associated to body aging, through molecular mechanisms such as telomere attrition, mitochondrial dysfunction, cellular senescence, chronic inflammation, and dysbiosis, among others. Regarding its impact in the skin, stress impacts its structural integrity and physiological function. Despite this review focusing on several hallmarks of aging, emphasis was placed on skin microbiota dysbiosis. In this line, several studies, comprising different age groups, demographic contexts and body sites, have reported skin microbiota alterations associated with aging, and some effects of stress mediators on skin microbiota have also been reviewed in this paper. From a different perspective, since it is not a “traditional” stress mediator, oxytocin, a cortisol antagonist, has been related to glucorticoids inhibition and to display positive effects on cellular aging. This hormone dysregulation has been associated to psychological issues such as depression, whereas its upregulation has been linked to positive social interaction.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"220 ","pages":"Article 111956"},"PeriodicalIF":5.3,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0047637424000563/pdfft?md5=c26c1e1c2a21527b3177f1c4590b6713&pid=1-s2.0-S0047637424000563-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437060","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

Time-dependent effects of high-fat diet on cognition and cerebral insulin signaling: Window for recovery and potential therapeutic target 高脂饮食对认知和脑胰岛素信号转导的时间依赖性影响：恢复窗口和潜在治疗目标。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-06-07 DOI: 10.1016/j.mad.2024.111955

Tianchuang Zhao , Qi Li , Xiaodan Wang , Bo Tang , Xueming Zhang , Hao Yu , Ziyi Li

{"title":"Time-dependent effects of high-fat diet on cognition and cerebral insulin signaling: Window for recovery and potential therapeutic target","authors":"Tianchuang Zhao , Qi Li , Xiaodan Wang , Bo Tang , Xueming Zhang , Hao Yu , Ziyi Li","doi":"10.1016/j.mad.2024.111955","DOIUrl":"10.1016/j.mad.2024.111955","url":null,"abstract":"<div><p>While high-fat diet (HFD)-induced obesity is a major threat to global public health, the effect of HFD on cognition and insulin signaling during ageing remains controversial. The aim of this study was to characterize the dynamic alterations in cognition and cerebral insulin signaling during 6-month HFD consumption, and to investigate the potential therapeutic target and optimal timing to rescue obesity-related cognitive deficits. In the present study, impaired memory retention induced by 2-month HFD was recovered after 4 months on HFD. Prolonged (6-month) HFD did not further enhance tau hyperphosphorylation and β-amyloid deposition, which was consistent with the alleviation of memory retention. In brain insulin signaling, 2-month HFD increased IRS-1 and p-IRS-1(Ser307)/IRS-1, while decreasing pAKT(Ser473)/AKT, PI3K and mTOR; 4-month HFD decreased IRS-1 and pAKT(Ser473)/AKT, while increasing AKT; 6-month HFD increased IRS-1, pAKT(Ser473)/AKT, and mTOR, while decreasing p-IRS-1(Ser307)/IRS-1, PI3K and AKT. Notably, bioinformatic analysis revealed a rhythmic process presented only in 4-month HFD group, with <em>Srebf1</em> emerging as a link between circadian rhythms and insulin signaling pathway. These results suggest that prolonged HFD prevents further cognitive decline and the progression of Alzheimer’s disease (AD)-related pathologies during ageing. Moreover, there may be a window for recovery, in which <em>Srebf1</em> acts as a self-recovery switch to address obesity-related cognitive disorders in elders.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"220 ","pages":"Article 111955"},"PeriodicalIF":5.3,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296312","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

CAR, mGPS and hs-mGPS: What is among them the best gero-biomarker for age-related diseases? And for what clinical application? CAR、mGPS 和 hs-mGPS：它们中哪个是老年相关疾病的最佳血细胞生物标记物？有何临床应用？

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-06-04 DOI: 10.1016/j.mad.2024.111952

Miriam Carella , Daniele Magro , Letizia Scola , Calogera Pisano , Eugenia Guida , Francesco Gervasi , Caterina Giambanco , Tommaso Silvano Aronica , Giacomo Frati , Carmela Rita Balistreri

{"title":"CAR, mGPS and hs-mGPS: What is among them the best gero-biomarker for age-related diseases? And for what clinical application?","authors":"Miriam Carella , Daniele Magro , Letizia Scola , Calogera Pisano , Eugenia Guida , Francesco Gervasi , Caterina Giambanco , Tommaso Silvano Aronica , Giacomo Frati , Carmela Rita Balistreri","doi":"10.1016/j.mad.2024.111952","DOIUrl":"10.1016/j.mad.2024.111952","url":null,"abstract":"<div><p>The identification of biomarkers linked to the onset, progression, and prevention of age-related diseases (ARD), in the era of personalized medicine, represents the best goal of geroscience. Geroscience has the fundamental role of exploring and identifying the biological mechanisms of aging to suggest interventions capable of stopping/delaying the many pathological conditions and disabilities related to age. Therefore, it has become its key priority, as well as that of clinical practice and research, based on identifying and validating a range of biomarkers, geromarkers, which can be used to diagnostic, prognostic, or predictive clinical purposes. Indeed, geromarkers have, the potential to predict ARD trajectories and facilitate targeted interventions to slow down the related disabilities. Here our attention is paid to the inflammatory indexes (CAR, mGPS, hs-mGPS) linked to the relationship between the plasma levels of two inflammatory analytes, the typical positive protein of the acute phase, and the negative one, i.e. c-reactive protein (CRP) and albumin, respectively. These indexes allow us to understand the magnitude of the two main mechanisms predicted to influence the aging process, including inflammation and immunosenescence, as well as the degree of ARD severity. Evidence on their relationship with ARD is widely reported and discussed, to understand which can represent the best ARD geromarker, and its clinical application.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"220 ","pages":"Article 111952"},"PeriodicalIF":5.3,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262174","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

Competing endogenous RNA networks were associated with fat accumulation in skeletal muscle of aged male mice 竞争性内源性 RNA 网络与老年雄性小鼠骨骼肌中的脂肪积累有关

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-06-03 DOI: 10.1016/j.mad.2024.111953

Yuxiao Liao , Zhao Peng , Xiaolei Zhou , Huanhuan Zhou , Zitong Meng , Shiyin Xu , Taoping Sun , Andreas K. Nüssler , Wei Yang

{"title":"Competing endogenous RNA networks were associated with fat accumulation in skeletal muscle of aged male mice","authors":"Yuxiao Liao , Zhao Peng , Xiaolei Zhou , Huanhuan Zhou , Zitong Meng , Shiyin Xu , Taoping Sun , Andreas K. Nüssler , Wei Yang","doi":"10.1016/j.mad.2024.111953","DOIUrl":"10.1016/j.mad.2024.111953","url":null,"abstract":"<div><p>Muscle aging contributed to morbidity and mortality in the elderly adults by leading to severe outcomes such as frailty, falls and fractures. Post-transcriptional regulation especially competing endogenous RNA (ceRNA) mechanism may modulate the process of skeletal muscle aging. RNA-seq was performed in quadriceps of 6-month-old (adult) and 22-month-old (aged) male mice to identify differentially expressed ncRNAs and mRNAs and further construct ceRNA networks. Decreased quadriceps-body weight ratio and muscle fiber cross-sectional area as well as histological characteristics of aging were observed in the aged mice. Besides, there were higher expressions of atrogin-1 and MuRF-1 and lower expression of Myog, Myf4 and Myod1 in the quadriceps of aged mice relative to that of adult mice. The expression of 85 lncRNAs, 52 circRNAs, 10 miRNAs and 277 mRNAs were significantly dysregulated in quadriceps between the two groups, among which two ceRNA networks lncRNA 2700081O15Rik/circRNA_0000820-miR-673–3p-Tmem120b were constructed. Level of triglycerides and expression of PPARγ, C/EBPα, FASN and leptin were elevated and the expression of adiponectin was reduced in quadriceps of aged mice compared with that of adult mice. LncRNA 2700081O15Rik/circRNA_0000820-miR-673–3p-Tmem120b were possibly associated with the adipogenesis and fat accumulation in skeletal muscle of age male mice.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"220 ","pages":"Article 111953"},"PeriodicalIF":5.3,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141228738","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-dependent regulation of pancreatic islet landscape is fueled by a HNF1a-immune signaling loop HNF1a-免疫信号环路对胰岛景观的年龄依赖性调控起到了推波助澜的作用。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-05-31 DOI: 10.1016/j.mad.2024.111951

Andreas Frøslev Mathisen , Thomas Aga Legøy , Ulrik Larsen , Lucas Unger , Shadab Abadpour , Joao A. Paulo , Hanne Scholz , Luiza Ghila , Simona Chera

{"title":"The age-dependent regulation of pancreatic islet landscape is fueled by a HNF1a-immune signaling loop","authors":"Andreas Frøslev Mathisen , Thomas Aga Legøy , Ulrik Larsen , Lucas Unger , Shadab Abadpour , Joao A. Paulo , Hanne Scholz , Luiza Ghila , Simona Chera","doi":"10.1016/j.mad.2024.111951","DOIUrl":"10.1016/j.mad.2024.111951","url":null,"abstract":"<div><p>Animal longevity is a function of global vital organ functionality and, consequently, a complex polygenic trait. Yet, monogenic regulators controlling overall or organ-specific ageing exist, owing their conservation to their function in growth and development. Here, by using pathway analysis combined with wet-biology methods on several dynamic timelines, we identified Hnf1a as a novel master regulator of the maturation and ageing in the adult pancreatic islet during the first year of life. Conditional transgenic mice bearing suboptimal levels of this transcription factor in the pancreatic islets displayed age-dependent changes, with a profile echoing precocious maturation. Additionally, the comparative pathway analysis revealed a link between <em>Hnf1a</em> age-dependent regulation and immune signaling, which was confirmed in the ageing timeline of an overly immunodeficient mouse model. Last, the global proteome analysis of human islets spanning three decades of life largely backed the age-specific regulation observed in mice. Collectively, our results suggest a novel role of Hnf1a as a monogenic regulator of the maturation and ageing process in the pancreatic islet via a direct or indirect regulatory loop with immune signaling.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"220 ","pages":"Article 111951"},"PeriodicalIF":5.3,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0047637424000514/pdfft?md5=0363bcb9badc4604c645f6e284d30866&pid=1-s2.0-S0047637424000514-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200243","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

Local cannabinoid receptor type-1 regulates glial cell activity and insulin-like growth factor-1 receptor signaling in the mediobasal hypothalamus 局部大麻素受体1型调节下丘脑中间神经胶质细胞的活动和胰岛素样生长因子-1受体的信号转导。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-05-29 DOI: 10.1016/j.mad.2024.111954

Michela Palmisano , Carla Florencia Ramunno , Eli Farhat , Mona Dvir-Ginzberg , Beat Lutz , Carmen Ruiz de Almodovar , Andras Bilkei-Gorzo

{"title":"Local cannabinoid receptor type-1 regulates glial cell activity and insulin-like growth factor-1 receptor signaling in the mediobasal hypothalamus","authors":"Michela Palmisano , Carla Florencia Ramunno , Eli Farhat , Mona Dvir-Ginzberg , Beat Lutz , Carmen Ruiz de Almodovar , Andras Bilkei-Gorzo","doi":"10.1016/j.mad.2024.111954","DOIUrl":"10.1016/j.mad.2024.111954","url":null,"abstract":"<div><p>As organisms age, the activity of the endocannabinoid system in the brain declines, coinciding with increased neuroinflammation and disrupted hypothalamic functions. Notably, cannabinoid receptors type-1 (CB1) are highly expressed in the ventromedial hypothalamic nucleus (VMH) within the mediobasal hypothalamus, a central area of neuroendocrine regulation. This study investigates whether the CB1 receptor influences age-related changes in a brain region-dependent manner. Therefore, we performed stereotaxic injections of rAAV1/2 expressing Cre recombinase in 2-month-old CB1<sup>flox/flox</sup> male animals to delete the CB1 gene and in CB1-deficient (CB1-STOP) mice to induce its re-expression. The intensity of pro-inflammatory glial activity, gonadotropin-releasing hormone (GnRH) and insulin-like growth factor-1 receptor (IGF-1R) expression was assessed in the hypothalamus of mice at 18–19 months of age. Site-specific CB1 receptor deletion induced pro-inflammatory glial activity and increased hypothalamic <em>Igf1r</em> mRNA expression. Unexpectedly, GnRH levels remained unaltered. Importantly, rescuing the receptor in null mutant animals had the opposite effect: it reduced pro-inflammatory glial activation and decreased <em>Igf1r</em> mRNA expression without affecting GnRH production. Overall, the study highlights the important role of the CB1 receptor in the VMH in reducing age-related inflammation and modulating IGF-1R signaling.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"220 ","pages":"Article 111954"},"PeriodicalIF":5.3,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S004763742400054X/pdfft?md5=33f2523946297d859c99ff88b3a16767&pid=1-s2.0-S004763742400054X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141184094","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

Elucidating the role of chemokines in inflammaging associated atherosclerotic cardiovascular diseases 阐明趋化因子在与炎症相关的动脉粥样硬化性心血管疾病中的作用。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-05-21 DOI: 10.1016/j.mad.2024.111944

Nupur Nagar , Goutami Naidu , Santosh Kumar Panda , Khushboo Gulati , Ravindra Pal Singh , Krishna Mohan Poluri

{"title":"Elucidating the role of chemokines in inflammaging associated atherosclerotic cardiovascular diseases","authors":"Nupur Nagar , Goutami Naidu , Santosh Kumar Panda , Khushboo Gulati , Ravindra Pal Singh , Krishna Mohan Poluri","doi":"10.1016/j.mad.2024.111944","DOIUrl":"10.1016/j.mad.2024.111944","url":null,"abstract":"<div><p>Age-related inflammation or inflammaging is a critical deciding factor of physiological homeostasis during aging. Cardiovascular diseases (CVDs) are exquisitely associated with aging and inflammation and are one of the leading causes of high mortality in the elderly population. Inflammaging comprises dysregulation of crosstalk between the vascular and cardiac tissues that deteriorates the vasculature network leading to development of atherosclerosis and atherosclerotic-associated CVDs in elderly populations. Leukocyte differentiation, migration and recruitment holds a crucial position in both inflammaging and atherosclerotic CVDs through relaying the activity of an intricate network of inflammation-associated protein-protein interactions. Among these interactions, small immunoproteins such as chemokines play a major role in the progression of inflammaging and atherosclerosis. Chemokines are actively involved in lymphocyte migration and severe inflammatory response at the site of injury. They relay their functions via chemokine-G protein-coupled receptors-glycosaminoglycan signaling axis and is a principal part for the detection of age-related atherosclerosis and related CVDs. This review focuses on highlighting the detailed intricacies of the effects of chemokine-receptor interaction and chemokine oligomerization on lymphocyte recruitment and its evident role in clinical manifestations of atherosclerosis and related CVDs. Further, the role of chemokine mediated signaling for formulating next-generation therapeutics against atherosclerosis has also been discussed.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"220 ","pages":"Article 111944"},"PeriodicalIF":5.3,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141087577","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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