Mechanisms of Ageing and Development最新文献_第2页

Deletion of stimulator of interferons genes aggravated cardiac dysfunction in physiological aged mice 删除干扰素刺激基因会加重生理衰老小鼠的心脏功能障碍

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-09-02 DOI: 10.1016/j.mad.2024.111978

{"title":"Deletion of stimulator of interferons genes aggravated cardiac dysfunction in physiological aged mice","authors":"","doi":"10.1016/j.mad.2024.111978","DOIUrl":"10.1016/j.mad.2024.111978","url":null,"abstract":"<div><h3>Background</h3><p>Stimulator of interferons genes (STING) is crucial for innate immune response. It has been demonstrated that cGAS-STING pathway was the driver of aging-related inflammation. However, whether STING is involved in cardiac dysfunction during the physiological aging process remains unclear.</p></div><div><h3>Methods</h3><p>Gene expression profiles were obtained from the Gene Expression Omnibus database, followed by weighted gene co-expression network analysis, gene ontology analysis and protein network interaction analysis to identify key pathway and genes associated with aging. The effects of STING on cardiac function, glucose homeostasis, inflammation, and autophagy in physiological aging were investigated with STING knockout mice.</p></div><div><h3>Results</h3><p>Bioinformatics analysis revealed STING emerged as a hub gene of interest. Subsequent experiments demonstrated the activation of STING pathway in the heart of aged mice. Knockout of STING alleviated the inflammation in aged mice. However, Knockout of STING impaired glucose tolerance, inhibited autophagy, enhanced oxidative stress and aggravated cardiac dysfunction in aged mice.</p></div><div><h3>Conclusion</h3><p>Although reducing inflammation, long-term STING inhibition by genetic ablation exacerbated cardiac dysfunction in aged mice. Given the multifaceted nature of aging and the diverse cellular functions of STING beyond immune regulation, the negative effects of targeting STING as a strategy to mitigate aging phenotype should be fully considered.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133175","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

Corrigendum to “CAR, mGPS and hs-mGPS: Which of these is the best gero-biomarker for age-related diseases? And for what clinical application?” [Mech. Aging Dev. 220 (2024) 111952] CAR、mGPS 和 hs-mGPS：哪一种是老年相关疾病的最佳血细胞生物标记物？又有哪些临床应用？[220（2024）111952]。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-08-13 DOI: 10.1016/j.mad.2024.111977

引用次数: 0

Senescence of skeletal stem cells and their contribution to age-related bone loss 骨骼干细胞的衰老及其对年龄相关性骨质流失的贡献。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-08-05 DOI: 10.1016/j.mad.2024.111976

引用次数: 0

The emerging importance of lymphangiogenesis in aging and aging-associated diseases 淋巴管生成在衰老和衰老相关疾病中的重要性正在显现。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-07-31 DOI: 10.1016/j.mad.2024.111975

{"title":"The emerging importance of lymphangiogenesis in aging and aging-associated diseases","authors":"","doi":"10.1016/j.mad.2024.111975","DOIUrl":"10.1016/j.mad.2024.111975","url":null,"abstract":"<div><p>Lymphatic aging represented by cellular and functional changes, is involved in increased geriatric disorders, but the intersection between aging and lymphatic modulation is less clear. Lymphatic vessels play an essential role in maintaining tissue fluid homeostasis, regulating immune function, and promoting macromolecular transport. Lymphangiogenesis and lymphatic remodeling following cellular senescence and organ deterioration are crosslinked with the progression of some lymphatic-associated diseases, e.g., atherosclerosis, inflammation, lymphoedema, and cancer. Age-related detrimental tissue changes may occur in lymphatic vessels with diverse etiologies, and gradually shift towards chronic low-grade inflammation, so-called inflammaging, and lead to decreased immune response. The investigation of the relationship between advanced age and organ deterioration is becoming an area of rapidly increasing significance in lymphatic biology and medicine. Here we highlight the emerging importance of lymphangiogenesis and lymphatic remodeling in the regulation of aging-related pathological processes, which will help to find new avenues for effective intervention to promote healthy aging.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0047637424000757/pdfft?md5=0d4002bfef4ad48067677f7387267ada&pid=1-s2.0-S0047637424000757-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875331","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}

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Potential protein biomarkers in saliva for detection of frailty syndrome by targeted proteomics 通过靶向蛋白质组学检测虚弱综合征的唾液中潜在蛋白质生物标记物

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-07-20 DOI: 10.1016/j.mad.2024.111974

{"title":"Potential protein biomarkers in saliva for detection of frailty syndrome by targeted proteomics","authors":"","doi":"10.1016/j.mad.2024.111974","DOIUrl":"10.1016/j.mad.2024.111974","url":null,"abstract":"<div><p>Frailty is a physiological geriatric syndrome, caused by immunosenescence, inflammation and alterations at the protein level leading to metabolic and microbiota changes. Currently, this syndrome is evaluated clinically with the Frailty-VIG index. The aim of the study was therefore to investigate the potential suitability of saliva as a non-invasive proximal biological fluid for the characterisation and identification of possible protein-level biomarkers in frailty syndrome. This cross-sectional study was conducted in a rural population of older Spanish adults using the SMR proteomics technique. A differential protein profile of eight potential and surrogate proteins (CYTC, CYTD, CYTS, CYTB, MIF, ALBU, CD44 and B2MG) was detected in saliva, all of which correlated with factors characterising frailty syndrome, such as vascular ageing (arterial stiffness and cardiovascular disease), obesity, mood problems, global cognitive impairment, changes in gait and hand pressure strength. The proteins CYTD (r = 0.415, p = 0.013) and CYTC (r = 0.280, p = 0.026), which were detected differentially in the protein profile, were associated with the Frailty-VIG index. All analysed proteins are associated not only with the clinical symptoms of frailty syndrome, but also with an acute inflammatory response, endothelial cell proliferation and the complement system, among others.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748540","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

Sestrin2 plays a protective role in age-related hearing loss by inhibiting NLRP3-inflammasome activity Sestrin2 通过抑制 NLRP3-炎症小体的活性，在老年性听力损失中发挥保护作用。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-07-15 DOI: 10.1016/j.mad.2024.111964

引用次数: 0

REDD1 knockdown ameliorates endothelial cell senescence through repressing TXNIP-mediated oxidative stress 通过抑制 TXNIP 介导的氧化应激，敲除 REDD1 可改善内皮细胞衰老。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-07-14 DOI: 10.1016/j.mad.2024.111962

{"title":"REDD1 knockdown ameliorates endothelial cell senescence through repressing TXNIP-mediated oxidative stress","authors":"","doi":"10.1016/j.mad.2024.111962","DOIUrl":"10.1016/j.mad.2024.111962","url":null,"abstract":"<div><p>Endothelial cell senescence characterized by reactive oxygen species (ROS) accumulation and chronic inflammation is widely recognized as a key contributor to atherosclerosis (AS). Regulated in development and DNA damage response 1 (REDD1), a conserved stress-response protein that regulates ROS production, is involved in the pathogenesis of various age-related diseases. However, the role of REDD1 in endothelial cell senescence is still unclear. Here, we screened REDD1 as a differentially expressed senescence-related gene in the AS progression using bioinformatics methods, and validated the upregulation of REDD1 expression in AS plaques, senescent endothelial cells, and aging aorta by constructing AS mice, D-galactose (DG)-induced senescent endothelial cells and DG-induced accelerated aging mice, respectively. siRNA against REDD1 could improve DG-induced premature senescence of endothelial cells and inhibit ROS accumulation, similar to antioxidant N-Acetylcysteine (NAC) treatment. Meanwhile, NAC reduced the upregulation of REDD1 induced by DG, supporting the positive feedback loop between REDD1 and ROS contributes to endothelial cell senescence. Mechanistically, the regulatory effect of REDD1 on ROS might be related to the TXNIP-REDD1 interaction in DG-induced endothelial cell senescence. Collectively, experiments above provide evidence that REDD1 participates in endothelial cell senescence through repressing TXNIP-mediated oxidative stress, which may be involved in the progression of atherosclerosis.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616781","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

A mechanistic analysis of metformin's biphasic effects on lifespan and healthspan in C. elegans: Elixir in youth, poison in elder 二甲双胍对 elegans 寿命和健康寿命双相影响的机制分析：年轻时的灵丹妙药，年老时的毒药。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-07-08 DOI: 10.1016/j.mad.2024.111963

{"title":"A mechanistic analysis of metformin's biphasic effects on lifespan and healthspan in C. elegans: Elixir in youth, poison in elder","authors":"","doi":"10.1016/j.mad.2024.111963","DOIUrl":"10.1016/j.mad.2024.111963","url":null,"abstract":"<div><p>Aging, a complex biological process influenced by genetic, environmental, and pharmacological factors, presents a significant challenge in understanding its underlying mechanisms. In this study, we explored the divergent impacts of metformin treatment on the lifespan and healthspan of young and old <em>C. elegans</em>, demonstrating a intriguing “elixir in youth, poison in elder” phenomenon. By scrutinizing the gene expression changes in response to metformin in young (day 1 of adulthood) and old (days 8) groups, we identified <em>nhr-57</em> and <em>C46G7.1</em> as potential modulators of age-specific responses. Notably, <em>nhr-57</em> and <em>C46G7.1</em> exhibit contrasting regulation patterns, being up-regulated in young worms but down-regulated in old counterparts following metformin treatment. Functional studies employing knockdown approaches targeting <em>nhr-57</em>, a gene under the control of <em>hif-1</em> with a documented protective function against pore-forming toxins in <em>C. elegans</em>, and <em>C46G7.1</em>, unveiled their critical roles in modulating lifespan and healthspan, as well as in mediating the biphasic effects of metformin. Furthermore, deletion of <em>hif-1</em> retarded the influence of metformin, implicating the involvement of <em>hif-1</em>/<em>nhr-57</em> in age-specific drug responses. These findings underscored the necessity of deciphering the mechanisms governing age-related susceptibility to pharmacological agents to tailor interventions for promoting successful aging.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580197","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

Transgenerational hormesis in healthy aging and antiaging medicine from bench to clinics: Role of food components 从实验室到临床，健康老龄化和抗衰老医学中的跨代激素作用：食物成分的作用。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-07-05 DOI: 10.1016/j.mad.2024.111960

Vittorio Calabrese , Naomi Osakabe , Rosalba Siracusa , Sergio Modafferi , Rosanna Di Paola , Salvatore Cuzzocrea , Ursula M. Jacob , Tilman Fritsch , Ali S. Abdelhameed , Luay Rashan , Uwe Wenzel , Claudio Franceschi , Edward J. Calabrese

{"title":"Transgenerational hormesis in healthy aging and antiaging medicine from bench to clinics: Role of food components","authors":"Vittorio Calabrese , Naomi Osakabe , Rosalba Siracusa , Sergio Modafferi , Rosanna Di Paola , Salvatore Cuzzocrea , Ursula M. Jacob , Tilman Fritsch , Ali S. Abdelhameed , Luay Rashan , Uwe Wenzel , Claudio Franceschi , Edward J. Calabrese","doi":"10.1016/j.mad.2024.111960","DOIUrl":"10.1016/j.mad.2024.111960","url":null,"abstract":"<div><p>Neurodegenerative diseases have multifactorial pathogenesis, mainly involving neuroinflammatory processes. Finding drugs able to treat these diseases, expecially because for most of these diseases there are no effective drugs, and the current drugs cause undesired side effects, represent a crucial point. Most <em>in vivo</em> and <em>in vitro</em> studies have been concentrated on various aspects related to neurons (e.g. neuroprotection), however, there has not been focus on the prevention of early stages involving glial cell activation and neuroinflammation. Recently, it has been demonstrated that nutritional phytochemicals including polyphenols, the main active constituents of the Mediterranean diet, maintain redox balance and neuroprotection through the activation of hormetic vitagene pathway. Recent lipidomics data from our laboratory indicate mushrooms as strong nutritional neuronutrients with strongly activity against neuroinflammation in Meniere’ diseaseas, a model of cochleovestibular neural degeneration, as well as in animal model of traumatic brain injury, or rotenone induced parkinson’s disease. Moreover, Hidrox®, an aqueous extract of olive containing hydroxytyrosol, and Boswellia, acting as Nrf2 activators, promote resilience by enhancing the redox potential, and thus, regulate through hormetic mechanisms, cellular stress response mechanisms., Thus, modulation of cellular stress pathways, in particular vitagenes system, may be an innovative approach for therapeutic intervention in neurodegenerative disorders.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141545020","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

New opportunities for antioxidants in amelioration of neurodegenerative diseases 抗氧化剂在改善神经退行性疾病方面的新机遇。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-07-02 DOI: 10.1016/j.mad.2024.111961

{"title":"New opportunities for antioxidants in amelioration of neurodegenerative diseases","authors":"","doi":"10.1016/j.mad.2024.111961","DOIUrl":"10.1016/j.mad.2024.111961","url":null,"abstract":"<div><p>This comprehensive review elucidates the critical role of antioxidants to mitigate oxidative stress, a common denominator in an array of neurodegenerative disorders. Oxidative stress-induced damage has been linked to the development of diseases such as Alzheimer's, Parkinson's, Huntington's disease and amyotrophic lateral sclerosis. This article examines a wide range of scientific literature and methodically delineates the several methods by which antioxidants exercise their neuroprotective benefits. It also explores into the complex relationship between oxidative stress and neuroinflammation, focusing on how antioxidants can alter signaling pathways and transcription factors to slow neurodegenerative processes. Key antioxidants, such as vitamins C and E, glutathione, and polyphenolic compounds, are tested for their ability to combat reactive oxygen and nitrogen species. The dual character of antioxidants, which operate as both direct free radical scavengers and regulators of cellular redox homeostasis, is investigated in terms of therapeutic potential. Furthermore, the study focuses on new antioxidant-based therapy techniques and their mechanisms including Nrf-2, PCG1α, Thioredoxin etc., which range from dietary interventions to targeted antioxidant molecules. Insights into ongoing clinical studies evaluating antioxidant therapies in neurodegenerative illnesses offer an insight into the translational potential of antioxidant research. Finally, this review summarizes our present understanding of antioxidant processes in neurodegenerative illnesses, providing important possibilities for future study and treatment development.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498368","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