Mechanisms of Ageing and Development最新文献

筛选
英文 中文
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 ,&nbsp;Zhao Peng ,&nbsp;Xiaolei Zhou ,&nbsp;Huanhuan Zhou ,&nbsp;Zitong Meng ,&nbsp;Shiyin Xu ,&nbsp;Taoping Sun ,&nbsp;Andreas K. Nüssler ,&nbsp;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 ,&nbsp;Thomas Aga Legøy ,&nbsp;Ulrik Larsen ,&nbsp;Lucas Unger ,&nbsp;Shadab Abadpour ,&nbsp;Joao A. Paulo ,&nbsp;Hanne Scholz ,&nbsp;Luiza Ghila ,&nbsp;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 ,&nbsp;Carla Florencia Ramunno ,&nbsp;Eli Farhat ,&nbsp;Mona Dvir-Ginzberg ,&nbsp;Beat Lutz ,&nbsp;Carmen Ruiz de Almodovar ,&nbsp;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 ,&nbsp;Goutami Naidu ,&nbsp;Santosh Kumar Panda ,&nbsp;Khushboo Gulati ,&nbsp;Ravindra Pal Singh ,&nbsp;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}
引用次数: 0
SIRT-associated attenuation of cellular senescence in vascular wall 与 SIRT 相关的血管壁细胞衰老抑制作用
IF 5.3 3区 医学
Mechanisms of Ageing and Development Pub Date : 2024-05-17 DOI: 10.1016/j.mad.2024.111943
Iliyana Sazdova , Nikola Hadzi-Petrushev , Milena Keremidarska-Markova , Radoslav Stojchevski , Ramadan Sopi , Stanislav Shileiko , Vadim Mitrokhin , Hristo Gagov , Dimitar Avtanski , Lubomir T. Lubomirov , Mitko Mladenov
{"title":"SIRT-associated attenuation of cellular senescence in vascular wall","authors":"Iliyana Sazdova ,&nbsp;Nikola Hadzi-Petrushev ,&nbsp;Milena Keremidarska-Markova ,&nbsp;Radoslav Stojchevski ,&nbsp;Ramadan Sopi ,&nbsp;Stanislav Shileiko ,&nbsp;Vadim Mitrokhin ,&nbsp;Hristo Gagov ,&nbsp;Dimitar Avtanski ,&nbsp;Lubomir T. Lubomirov ,&nbsp;Mitko Mladenov","doi":"10.1016/j.mad.2024.111943","DOIUrl":"10.1016/j.mad.2024.111943","url":null,"abstract":"<div><p>This review focuses on the vital function that SIRT1 and other sirtuins play in promoting cellular senescence in vascular smooth muscle cells, which is a key element in the pathogenesis of vascular aging and associated cardiovascular diseases. Vascular aging is a gradual process caused by the accumulation of senescent cells, which results in increased vascular remodeling, stiffness, and diminished angiogenic ability. Such physiological alterations are characterized by a complex interplay of environmental and genetic variables, including oxidative stress and telomere attrition, which affect gene expression patterns and trigger cell growth arrest. SIRT1 has been highlighted for its potential to reduce cellular senescence through modulation of multiple signaling cascades, particularly the endothelial nitric oxide (eNOS)/NO signaling pathway. It also modulates cell cycle through p53 inactivation and suppresses NF-κB mediated expression of adhesive molecules at the vascular level. The study also examines the therapeutic potential of sirtuin modulation in vascular health, identifying SIRT1 and its sirtuin counterparts as potential targets for reducing vascular aging. This study sheds light on the molecular basis of vascular aging and the beneficial effects of sirtuins, paving the way for the development of tailored therapies aimed at enhancing vascular health and prolonging life.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"220 ","pages":"Article 111943"},"PeriodicalIF":5.3,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140958321","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
Understanding the (epi)genetic dysregulation in Parkinson's disease through an integrative brain competitive endogenous RNA network 通过综合大脑竞争性内源性 RNA 网络了解帕金森病的(外)基因失调。
IF 5.3 3区 医学
Mechanisms of Ageing and Development Pub Date : 2024-05-16 DOI: 10.1016/j.mad.2024.111942
Rafael Mina Piergiorge , Ana Tereza Ribeiro de Vasconcelos , Cíntia Barros Santos-Rebouças
{"title":"Understanding the (epi)genetic dysregulation in Parkinson's disease through an integrative brain competitive endogenous RNA network","authors":"Rafael Mina Piergiorge ,&nbsp;Ana Tereza Ribeiro de Vasconcelos ,&nbsp;Cíntia Barros Santos-Rebouças","doi":"10.1016/j.mad.2024.111942","DOIUrl":"10.1016/j.mad.2024.111942","url":null,"abstract":"<div><p>Parkinson’s disease (PD) is a rapidly growing neurodegenerative disorder characterized by dopaminergic neuron loss in the substantia nigra <em>pars compacta</em> (SN) and aggregation of α-synuclein. Its aetiology involves a multifaceted interplay among genetic, environmental, and epigenetic factors. We integrated brain gene expression data from PD patients to construct a comprehensive regulatory network encompassing messenger RNAs (mRNAs), microRNAs (miRNAs), circular RNAs (circRNAs) and, for the first time, RNA binding proteins (RBPs). Expression data from the SN of PD patients and controls were systematically selected from public databases to identify combined differentially expressed genes (DEGs). Brain co-expression analysis revealed modules comprising significant DEGs that function cooperatively. The relationships among co-expressed DEGs, miRNAs, circRNAs, and RBPs revealed an intricate competitive endogenous RNA (ceRNA) network responsible for post-transcriptional dysregulation in PD. Many genes in the ceRNA network, including the <em>TOMM20</em> and <em>HMGCR</em> genes, overlap with the most relevant genes in our previous Alzheimer’s disease-associated ceRNA network, suggesting common underlying mechanisms between both conditions. Moreover, in the ceRNA subnetwork, the RBP Aly/REF export factor (ALYREF), which acts as an RNA 5-methylcytosine(m5C)-binding protein, stood out. Our data sheds new light on the potential role of brain ceRNA networks in PD pathogenesis.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"219 ","pages":"Article 111942"},"PeriodicalIF":5.3,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140958367","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
Sarcopenia: A dive into metabolism to promote a multimodal, preventive, and regenerative approach 肌肉疏松症:深入研究新陈代谢,促进多模式、预防和再生方法。
IF 5.3 3区 医学
Mechanisms of Ageing and Development Pub Date : 2024-05-14 DOI: 10.1016/j.mad.2024.111941
Virginia Boccardi
{"title":"Sarcopenia: A dive into metabolism to promote a multimodal, preventive, and regenerative approach","authors":"Virginia Boccardi","doi":"10.1016/j.mad.2024.111941","DOIUrl":"10.1016/j.mad.2024.111941","url":null,"abstract":"<div><p>Sarcopenia, the age-related loss of skeletal muscle mass and function, poses a significant challenge in the field of geriatrics and gerontology, impacting the health and independence of older adults. Understanding and addressing sarcopenia is crucial for optimizing clinical outcomes and enhancing the quality of life along with aging. By synthesizing current research findings and theoretical frameworks, this review elucidates the multifaceted mechanisms underlying sarcopenia, mainly focusing on energy balance and metabolic processes. Furthermore, the manuscript explores the implications of sarcopenia on overall health outcomes, functional decline, and quality of life in older individuals. The study concludes with a perspective on the role of preventive and regenerative medicine in sarcopenia, where the two main lifestyle pillars (exercise and diet) represent key factors.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"219 ","pages":"Article 111941"},"PeriodicalIF":5.3,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0047637424000411/pdfft?md5=8a870c8a1422b1e90f4e74dcfb0dd411&pid=1-s2.0-S0047637424000411-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945400","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
Comprehensive variant analysis of phospholipase A2 superfamily genes in large Chinese Parkinson’ s disease cohorts 大型中国帕金森病队列中磷脂酶 A2 超家族基因的全面变异分析
IF 5.3 3区 医学
Mechanisms of Ageing and Development Pub Date : 2024-05-14 DOI: 10.1016/j.mad.2024.111940
Jiabin Liu , Yige Wang , Yuwen Zhao , Hongxu Pan , Zhenhua Liu , Qian Xu , Shen Lu , Hong Jiang , Junling Wang , Qiying Sun , Jieqiong Tan , Xinxiang Yan , Jinchen Li , Beisha Tang , Jifeng Guo
{"title":"Comprehensive variant analysis of phospholipase A2 superfamily genes in large Chinese Parkinson’ s disease cohorts","authors":"Jiabin Liu ,&nbsp;Yige Wang ,&nbsp;Yuwen Zhao ,&nbsp;Hongxu Pan ,&nbsp;Zhenhua Liu ,&nbsp;Qian Xu ,&nbsp;Shen Lu ,&nbsp;Hong Jiang ,&nbsp;Junling Wang ,&nbsp;Qiying Sun ,&nbsp;Jieqiong Tan ,&nbsp;Xinxiang Yan ,&nbsp;Jinchen Li ,&nbsp;Beisha Tang ,&nbsp;Jifeng Guo","doi":"10.1016/j.mad.2024.111940","DOIUrl":"10.1016/j.mad.2024.111940","url":null,"abstract":"<div><p>To clarify the genetic role of phospholipase A2 (PLA2) genes in Parkinson's disease (PD), we performed a genetic association study in large Chinese population cohorts using next-generation sequencing. In this study, we analyzed both rare and common variants of 38 phospholipase A2 genes in two large cohorts. We detected 1558 and 1115 rare variants in these two cohorts, respectively. In both cohorts, we observed suggestive associations between specific subgroups and the risk of PD. At the single-gene level, several genes (<em>PLA2G2D, PLA2G12A, PLA2G12B, PLA2G4F, PNPLA1, PNPLA3, PNPLA7, PLA2G7, PLA2G15, PLAAT5,</em> and <em>ABHD12</em>) are suggestively associated with PD. Meanwhile, 364 and 2261 common variants were identified in two cohorts, respectively. Our study has expanded the genetic spectrum of the PLA2 family genes and suggested potential pathogenetic roles of PLA2 superfamily in PD.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"219 ","pages":"Article 111940"},"PeriodicalIF":5.3,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945353","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
Resveralogues protect HepG2 cells against cellular senescence induced by hepatotoxic metabolites 白藜芦醇保护 HepG2 细胞免受肝毒性代谢物诱导的细胞衰老。
IF 5.3 3区 医学
Mechanisms of Ageing and Development Pub Date : 2024-05-12 DOI: 10.1016/j.mad.2024.111938
Neda Heidari , Susan Sandeman , Marcus Dymond , Chloe Rogers , Elizabeth L. Ostler , Richard GA Faragher
{"title":"Resveralogues protect HepG2 cells against cellular senescence induced by hepatotoxic metabolites","authors":"Neda Heidari ,&nbsp;Susan Sandeman ,&nbsp;Marcus Dymond ,&nbsp;Chloe Rogers ,&nbsp;Elizabeth L. Ostler ,&nbsp;Richard GA Faragher","doi":"10.1016/j.mad.2024.111938","DOIUrl":"10.1016/j.mad.2024.111938","url":null,"abstract":"<div><p>Progressive liver disease and dysfunction cause toxic metabolites including ammonia and unconjugated bilirubin to accumulate in plasma. As the population ages alternatives to liver transplantation become increasingly important. One approach for use as a bridge to transplant or recovery is the use of bioartificial liver systems (BALS) containing primary or immortalised hepatocytes as ex-vivo replacements or supports for endogenous liver function. However, exposure to the hepatotoxic metabolites present in plasma causes the rapid failure of these cells to carry out their primary metabolic functions despite remaining viable. Hypothesizing that this loss of core hepatocyte phenotypes was caused by cell senescence we exposed HepG2 cell populations, grown in both standard two-dimensional tissue culture systems and in three dimensional cultures on novel alginate modified HEMA-MBA cryogels, to physiologically reflective concentrations of hepatotoxic metabolites and cytokines. HepG2 cells are forced into senescence by the toxic metabolites in under six hours (as measured by loss of thymidine analog incorporation or detectable Ki67 staining) which is associated with a ten to twenty-fold reduction in the capacity of the cultures to synthesise albumin or urea. This state of senescence induced by liver toxins (SILT) can be prevented by preincubation with either 2–5 µM resveratrol, its major in vivo metabolite dihydroresveratrol or a series of novel resveralogues with differential capacities to scavenge radicals and activate SIRT1 (including V29 which does not interact with the protein). SILT appears to be a previously unrecognised barrier to the development of BALS which can now be overcome using small molecules that are safe for human use at concentrations readily achievable in vivo.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"219 ","pages":"Article 111938"},"PeriodicalIF":5.3,"publicationDate":"2024-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0047637424000381/pdfft?md5=e2f136e12243c0cca551ca1d405527a6&pid=1-s2.0-S0047637424000381-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140920909","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
Inflammaging score as a potential prognostic tool for cancer: A population-based cohort study 作为癌症潜在预后工具的炎症评分:基于人群的队列研究
IF 5.3 3区 医学
Mechanisms of Ageing and Development Pub Date : 2024-05-12 DOI: 10.1016/j.mad.2024.111939
Hailun Xie , Lishuang Wei , Guotian Ruan , Heyang Zhang , Hanping Shi
{"title":"Inflammaging score as a potential prognostic tool for cancer: A population-based cohort study","authors":"Hailun Xie ,&nbsp;Lishuang Wei ,&nbsp;Guotian Ruan ,&nbsp;Heyang Zhang ,&nbsp;Hanping Shi","doi":"10.1016/j.mad.2024.111939","DOIUrl":"https://doi.org/10.1016/j.mad.2024.111939","url":null,"abstract":"<div><p>This study aimed to develop a clinically applicable inflammaging score by combining the inflammatory status and age of patients. Kaplan-Meier analysis was used to compare survival differences among patients with different grades of inflammation scores. Cox proportional hazard regression analysis was used to explore the relationship between the inflammaging score and survival. As the age of patients increased, their levels of systemic inflammation gradually increased. A unique inverse relationship was found between the level of inflammation and cancer prognosis during the ageing process. Mediation analysis indicated that systemic inflammation mediates 10.1%–17.8% of the association between ageing and poor prognosis. With an increase in the inflammaging score from grades I to V, the survival rate showed a gradient decline. The inflammation score could effectively stratify the prognosis of patients with lung, bronchial, gastrointestinal, and other types of cancers. Compared with grade I, the hazard ratios for grades II-V were 1.239, 1.604, 1.724, and 2.348, respectively. In the external validation cohort, the inflammaging score remained an independent factor affecting the prognosis of patients with cancer. The inflammaging score, which combines ageing and inflammation, is a robust prognostic assessment tool for cancer patients.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"219 ","pages":"Article 111939"},"PeriodicalIF":5.3,"publicationDate":"2024-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140918881","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
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信