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

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2023-10-01 DOI: 10.1016/j.mad.2023.111868

Ruoyu Li , Yungshan Teng , Yuqing Guo , Jianhan Ren , Runze Li , Haotian Luo , Danying Chen , Zhicai Feng , Zheng Fu , Xuenong Zou , Weicai Wang , Chen Zhou

{"title":"Aging-related decrease of histone methyltransferase SUV39H1 in adipose-derived stem cells enhanced SASP","authors":"Ruoyu Li , Yungshan Teng , Yuqing Guo , Jianhan Ren , Runze Li , Haotian Luo , Danying Chen , Zhicai Feng , Zheng Fu , Xuenong Zou , Weicai Wang , Chen Zhou","doi":"10.1016/j.mad.2023.111868","DOIUrl":"10.1016/j.mad.2023.111868","url":null,"abstract":"<div>Aging-related diseases are closely associated with the state of inflammation, which is known as “inflammaging.” Senescent cells are metabolically active, as exemplified by the secretion of inflammatory cytokines, chemokines, and growth factors, which is termed the senescence-associated secretory phenotype (SASP). Epigenetic regulation, especially the structural regulation of chromatin, is closely linked to the regulation of SASP. In our previous study, the suppressor of variegation 3–9 homolog 1 (SUV39H1) was elucidated to interact with Lhx8 and determine the cell fate of mesenchyme stem cells. However, the function of SUV39H1 during aging and the underlying mechanism of its epigenetic regulation remains controversial. Therefore, the C57BL/6 J CAG-Cre; SUV39H1fl/fl knockout mice and irradiation-induced cellular senescence model were built in this study to deepen the understanding of epigenetic regulation by SUV39H1 and its relation to SASP. In vivo and in vitro studies demonstrated that SUV39H1 decreased with aging and served as an inhibitor of SASP, especially IL-6, MCP-1, and Vcam-1, by altering H3K9me3 enrichment in their promoter region. These results provide new insights into the epigenetic regulation of SASP.</div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"215 ","pages":"Article 111868"},"PeriodicalIF":5.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10262954","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

Endoplasmic reticulum stress and alterations of peroxiredoxins in aged hearts 老年心脏的内质网应激和过氧化物酶体多氧酶的改变。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2023-10-01 DOI: 10.1016/j.mad.2023.111859

Qun Chen , Jeremy Thompson , Ying Hu , Edward J. Lesnefsky

{"title":"Endoplasmic reticulum stress and alterations of peroxiredoxins in aged hearts","authors":"Qun Chen , Jeremy Thompson , Ying Hu , Edward J. Lesnefsky","doi":"10.1016/j.mad.2023.111859","DOIUrl":"10.1016/j.mad.2023.111859","url":null,"abstract":"<div>Aging-related cardiovascular disease is influenced by multiple factors, with oxidative stress being a key contributor. Aging-induced endoplasmic reticulum (ER) stress exacerbates oxidative stress by impairing mitochondrial function. Furthermore, a decline in antioxidants, including peroxiredoxins (PRDXs), augments the oxidative stress during aging. To explore if ER stress leads to PRDX degradation during aging, young adult (3 mo.) and aged (24 mo.) male mice were studied. Treatment with 4-phenylbutyrate (4-PBA) was used to alleviate ER stress in young adult and aged mice. Aged hearts showed elevated oxidative stress levels compared to young hearts. However, treatment with 4-PBA to attenuate ER stress reduced oxidative stress in aged hearts, indicating that ER stress contributes to increased oxidative stress in aging. Moreover, aging resulted in reduced levels of peroxiredoxin 3 (PRDX3) in mitochondria and peroxiredoxin 4 (PRDX4) in myocardium. While 4-PBA treatment improved PRDX3 content in aged hearts, it did not restore PRDX4 content in aged mice. These findings suggest that ER stress not only leads to mitochondrial dysfunction and increased oxidant stress but also impairs a vital antioxidant defense through decreased PRDX3 content. Additionally, the results suggest that PRDX4 may contribute an upstream role in inducing ER stress during aging.</div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"215 ","pages":"Article 111859"},"PeriodicalIF":5.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10208020","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

Lipids and the hallmarks of ageing: From pathology to interventions 脂质和衰老的特征：从病理学到干预。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2023-10-01 DOI: 10.1016/j.mad.2023.111858

Rohit Sharma , Bhawna Diwan

{"title":"Lipids and the hallmarks of ageing: From pathology to interventions","authors":"Rohit Sharma , Bhawna Diwan","doi":"10.1016/j.mad.2023.111858","DOIUrl":"10.1016/j.mad.2023.111858","url":null,"abstract":"<div>Lipids are critical structural and functional architects of cellular homeostasis. Change in systemic lipid profile is a clinical indicator of underlying metabolic pathologies, and emerging evidence is now defining novel roles of lipids in modulating organismal ageing. Characteristic alterations in lipid metabolism correlate with age, and impaired systemic lipid profile can also accelerate the development of ageing phenotype. The present work provides a comprehensive review of the extent of lipids as regulators of the modern hallmarks of ageing viz., cellular senescence, chronic inflammation, gut dysbiosis, telomere attrition, genome instability, proteostasis and autophagy, epigenetic alterations, and stem cells dysfunctions. Current evidence on the modulation of each of these hallmarks has been discussed with emphasis on inherent age-dependent deficiencies in lipid metabolism as well as exogenous lipid changes. There appears to be sufficient evidence to consider impaired lipid metabolism as key driver of the ageing process although much of knowledge is yet fragmented. Considering dietary lipids, the type and quantity of lipids in the diet is a significant, but often overlooked determinant that governs the effects of lipids on ageing. Further research using integrative approaches amidst the known aging hallmarks is highly desirable for understanding the therapeutics of lipids associated with ageing.</div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"215 ","pages":"Article 111858"},"PeriodicalIF":5.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10235127","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

Cardiac iron metabolism during aging – Role of inflammation and proteolysis 衰老过程中的心脏铁代谢——炎症和蛋白水解的作用。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2023-10-01 DOI: 10.1016/j.mad.2023.111869

Sophia Walter , Christina Mertens , Martina U. Muckenthaler , Christiane Ott

{"title":"Cardiac iron metabolism during aging – Role of inflammation and proteolysis","authors":"Sophia Walter , Christina Mertens , Martina U. Muckenthaler , Christiane Ott","doi":"10.1016/j.mad.2023.111869","DOIUrl":"10.1016/j.mad.2023.111869","url":null,"abstract":"<div>Iron is the most abundant trace element in the human body. Since iron can switch between its 2-valent and 3-valent form it is essential in various physiological processes such as energy production, proliferation or DNA synthesis. Especially high metabolic organs such as the heart rely on iron-associated iron-sulfur and heme proteins. However, due to switches in iron oxidation state, iron overload exhibits high toxicity through formation of reactive oxygen species, underlining the importance of balanced iron levels. Growing evidence demonstrates disturbance of this balance during aging. While age-associated cardiovascular diseases are often related to iron deficiency, in physiological aging cardiac iron accumulates. To understand these changes, we focused on inflammation and proteolysis, two hallmarks of aging, and their role in iron metabolism. Via the IL-6-hepcidin axis, inflammation and iron status are strongly connected often resulting in anemia accompanied by infiltration of macrophages. This tight connection between anemia and inflammation highlights the importance of the macrophage iron metabolism during inflammation. Age-related decrease in proteolytic activity additionally affects iron balance due to impaired degradation of iron metabolism proteins. Therefore, this review accentuates alterations in iron metabolism during aging with regards to inflammation and proteolysis to draw attention to their implications and associations.</div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"215 ","pages":"Article 111869"},"PeriodicalIF":5.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10258499","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

Mitochondrial microRNAs (mitomiRs) in human ageing and diseases 人类衰老和疾病中的线粒体微小RNA。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2023-10-01 DOI: 10.1016/j.mad.2023.111873

Maria Gaitanou

引用次数: 0

The influence of inflammation and frailty in the aging continuum 炎症和虚弱对衰老的影响。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2023-10-01 DOI: 10.1016/j.mad.2023.111872

Beatrice Arosio , Evelyn Ferri , Daniela Mari , Eleonora Tobaldini , Giovanni Vitale , Nicola Montano

{"title":"The influence of inflammation and frailty in the aging continuum","authors":"Beatrice Arosio , Evelyn Ferri , Daniela Mari , Eleonora Tobaldini , Giovanni Vitale , Nicola Montano","doi":"10.1016/j.mad.2023.111872","DOIUrl":"10.1016/j.mad.2023.111872","url":null,"abstract":"<div>Inflammaging is a low-grade inflammatory state that can be considered an adaptive process aimed at stimulating appropriate anti-inflammatory response. Frailty is determined by the accumulation of molecular and cellular defects accumulated throughout life; therefore, an appropriate frailty computation could be a valuable tool for measuring biological age. This study aims to analyse the association between inflammatory markers and both chronological age \"per se\" and frailty. We studied 452 persons aged 43–114 years. A Frailty Index (FI) was computed considering a wide range of age-related signs, symptoms, disabilities, and diseases. Plasma concentrations of inflammatory cytokines and peripheral markers of neuroinflammation were analysed by next-generation ELISA. The mean age of the cohort was 79.7 (from 43 to 114) years and the median FI was 0.19 (from 0.00 to 0.75). The concentrations of most inflammatory markers increased significantly with chronological age, after adjustment for sex and FI. Interferon-γ was significantly affected only by FI, while interleukin (IL)-10 and IL-1β were associated only with chronological age. In conclusion, we described different associations between inflammatory components and chronological vs. biological age. A better characterization of the molecular signature of aging could help to understand the complexity of this process.</div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"215 ","pages":"Article 111872"},"PeriodicalIF":5.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10192395","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: 1

Exploring the interplay between metabolomics and genetics in Parkinson's disease: Insights from ongoing research and future avenues 探索帕金森病代谢组学和遗传学之间的相互作用：正在进行的研究和未来途径的见解。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2023-09-23 DOI: 10.1016/j.mad.2023.111875

Cíntia Barros Santos-Rebouças , Juliana Cordovil Cotrin , Gilson Costa dos Santos Junior

{"title":"Exploring the interplay between metabolomics and genetics in Parkinson's disease: Insights from ongoing research and future avenues","authors":"Cíntia Barros Santos-Rebouças , Juliana Cordovil Cotrin , Gilson Costa dos Santos Junior","doi":"10.1016/j.mad.2023.111875","DOIUrl":"10.1016/j.mad.2023.111875","url":null,"abstract":"<div>Parkinson's disease (PD) is a widespread neurodegenerative disorder, whose complex aetiology remains under construction. While rare variants have been associated with the monogenic PD form, most PD cases are influenced by multiple genetic and environmental aspects. Nonetheless, the pathophysiological pathways and molecular networks involved in monogenic/idiopathic PD overlap, and genetic variants are decisive in elucidating the convergent underlying mechanisms of PD. In this scenario, metabolomics has furnished a dynamic and systematic picture of the synergy between the genetic background and environmental influences that impact PD, making it a valuable tool for investigating PD-related metabolic dysfunctions. In this review, we performed a brief overview of metabolomics current research in PD, focusing on significant metabolic alterations observed in idiopathic PD from different biofluids and strata and exploring how they relate to genetic factors associated with monogenic PD. Dysregulated amino acid metabolism, lipid metabolism, and oxidative stress are the critical metabolic pathways implicated in both genetic and idiopathic PD. By merging metabolomics and genetics data, it is possible to distinguish metabolic signatures of specific genetic backgrounds and to pinpoint subgroups of PD patients who could derive personalized therapeutic benefits. This approach holds great promise for advancing PD research and developing innovative, cost-effective treatments.</div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"216 ","pages":"Article 111875"},"PeriodicalIF":5.3,"publicationDate":"2023-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41140484","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 link between obesity and aging - insights into cardiac energy metabolism 肥胖与衰老之间的联系——深入了解心脏能量代谢。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2023-09-07 DOI: 10.1016/j.mad.2023.111870

Patricia Owesny , Tilman Grune

引用次数: 0

Targeting senescence and inflammation in chronic destructive TNF-driven joint pathology 针对慢性破坏性tnf驱动的关节病理衰老和炎症

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2023-09-01 DOI: 10.1016/j.mad.2023.111856

Nikolaos I. Vlachogiannis , Konstantinos Evangelou , Lydia Ntari , Christoforos Nikolaou , Maria C. Denis , Niki Karagianni , Dimitris Veroutis , Vassilis Gorgoulis , George Kollias , Petros P. Sfikakis

{"title":"Targeting senescence and inflammation in chronic destructive TNF-driven joint pathology","authors":"Nikolaos I. Vlachogiannis , Konstantinos Evangelou , Lydia Ntari , Christoforos Nikolaou , Maria C. Denis , Niki Karagianni , Dimitris Veroutis , Vassilis Gorgoulis , George Kollias , Petros P. Sfikakis","doi":"10.1016/j.mad.2023.111856","DOIUrl":"10.1016/j.mad.2023.111856","url":null,"abstract":"<div>We had shown that administration of the senolytic Dasatinib abolishes arthritis in the human TNF transgenic mouse model of chronic destructive arthritis when given in combination with a sub-therapeutic dose of the anti-TNF mAb Infliximab (1 mg/kg). Herein, we found that while the number of senescent chondrocytes (GL13+/Ki67-), assessed according to guideline algorithmic approaches, was not affected by either Dasatinib or sub-therapeutic Infliximab monotherapies, their combination reduced senescent chondrocytes by 50 %, which was comparable to levels observed with therapeutic Infliximab monotherapy (10 mg/kg). This combination therapy also reduced the expression of multiple factors of senescence-associated secretory phenotype in arthritic joints. Studies to elucidate the interplay of inflammation and senescence may help in optimizing treatment strategies also for age-related pathologies characterized by chronic low-grade joint inflammation.</div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"214 ","pages":"Article 111856"},"PeriodicalIF":5.3,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10179117","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

Ageing-associated phenotypes in mice 小鼠衰老相关表型

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2023-09-01 DOI: 10.1016/j.mad.2023.111852

Kan Xie, Dan Ehninger

引用次数: 0