Mechanisms of Ageing and Development最新文献

{"title":"Prenatal Glucocorticoid Exposure and Congenital Abdominal Wall Defects: Involvement of CXCR4 - SDF-1 Signaling.","authors":"Martin Bablok, Gabriela Morosan-Puopolo, Imadeldin Yahya, Morris Gellisch, Matthias Nissen, Jochen Hubertus, Beate Brand-Saberi","doi":"10.1016/j.mad.2024.112008","DOIUrl":"https://doi.org/10.1016/j.mad.2024.112008","url":null,"abstract":"<p><p>Developmental defects of the ventral abdominal wall, such as gastroschisis, have been associated with prenatal stress exposure. To investigate this further, dexamethasone (DEX), a synthetic glucocorticoid, was administered to fertilized chicken eggs on day 1 of incubation to simulate stress, and embryonic development was subsequently analyzed through in-situ hybridization, immunohistochemistry, and histological methods. Significant developmental abnormalities were displayed by DEX-treated embryos, including open abdomens, reduced MYOG expression in the abdominal wall, and disrupted muscle fiber formation, as indicated by altered Myosin heavy chain patterns. Additionally, early markers of muscle development, such as Pax3, and the CXCR4-SDF-1 signaling axis, crucial for the migration of myogenic precursors of the dermomyotome, were markedly affected. Significant alterations in the expression of mesenchymal markers, including Vimentin and Fibronectin in the lateral plate mesoderm, were observed, alongside alterations in Pitx2, BMP4 and TFAP2A expression. Importantly, a downregulation of Glucocorticoid Receptors was identified, emphasizing the chronic stress exposure. These results provide critical insights into how DEX interferes with key developmental pathways, particularly those involving chemokines like CXCR4 and SDF-1, and other markers of mesodermal differentiation. An advancement in the understanding of the mechanisms underlying ventral abdominal wall defects in the context of prenatal stress is provided by this research, with potential implications for preventing these congenital anomalies.</p>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":" ","pages":"112008"},"PeriodicalIF":5.3,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695613","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}

{"title":"In reviewing the emerging biomarkers of human inflammatory bowel disease (IBD): Endothelial progenitor cells (EPC) and their vesicles as potential biomarkers of cardiovascular manifestations and targets for personalized treatments","authors":"Carmela Rita Balistreri","doi":"10.1016/j.mad.2024.112006","DOIUrl":"10.1016/j.mad.2024.112006","url":null,"abstract":"<div><div>Inflammatory bowel diseases (IBD) are chronic inflammatory and pathological conditions of the gastrointestinal tract, which include two main clinical subtypes: Crohn's disease (CD) and ulcerative colitis (UC). IBDs show an increase in their age-standardized global incidence rate worldwide, with no gender differences, although the age-standardized mortality rate has decreased over the years. Indeed, thanks to recent therapies with novel mechanisms of action, including those with biologics and small molecules, it has been possible to reduce the mortality rate of IBDs. However, a significant percentage of IBD patients remain refractory to these multiple advanced therapies. Therefore, another challenge of IBD research remains the development of novel therapies with novel agents or cells that could improve the quality of life and outcome of IBD patients. Furthermore, another aspect to be studied in IBDs is not only the high risk of progression not only to neoplastic transformation but also to the development of cardiovascular disease (CVD). Consequently, 25–40 % of IBD patients present with cardiovascular manifestations. Here, we propose that the altered number and functions of endothelial progenitor cells (EPCs) may represent one of the crucial mechanisms associated with incomplete/delayed healing of IBD and may offer the possibility of using them, as well as their vesicles and content, as novel biomarkers and potential candidates of cell therapy for IBD. The advantages and limitations are extensively described and discussed.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"222 ","pages":"Article 112006"},"PeriodicalIF":5.3,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693285","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}

{"title":"Unlocking diagnosis of sarcopenia: The role of circulating biomarkers – A clinical systematic review","authors":"F. Veronesi ,&nbsp;F. Salamanna ,&nbsp;V. Borsari ,&nbsp;A. Ruffilli ,&nbsp;C. Faldini ,&nbsp;G. Giavaresi","doi":"10.1016/j.mad.2024.112005","DOIUrl":"10.1016/j.mad.2024.112005","url":null,"abstract":"<div><div>Sarcopenia, the gradual loss of muscle mass, strength, and function with age, poses a significant risk to older adults, making early diagnosis crucial for preventing disability and enhancing quality of life. Biomarkers are vital for the early detection, monitoring progression, and assessing the efficacy of treatments for sarcopenia, offering a detailed evaluation of muscle health. This systematic review examined the clinical potential of circulating biomarkers in sarcopenia by analyzing studies up to May 2024 from PubMed, Scopus, Web of Science. A total of 45 studies involving 641,730 patients were reviewed, revealing notable biomarker differences between sarcopenic and non-sarcopenic individuals. Sarcopenic patients exhibited lower levels of certain microRNAs, hemoglobin, albumin, and anti-inflammatory factors, alongside higher levels of red and white blood cells, pro-inflammatory factors, growth factors, matrix proteins, free thyroxine, cortisol, and adiponectin. Additionally, they had lower levels of irisin, free triiodothyronine, and insulin, with reduced phosphatidylcholines and elevated spermidine. The studies were generally of fair to good quality, but due to heterogeneity, a meta-analysis was not feasible. The review underscores the need for standardized biomarkers and diagnostic criteria and suggests that improving outcomes for sarcopenic patients may involve addressing inflammation, metabolic, and hormonal issues through nutrition, medication, and exercise.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"222 ","pages":"Article 112005"},"PeriodicalIF":5.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623559","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}

{"title":"p53/HIF-1α regulates neuronal aging and autophagy in spinal cord ischemia/reperfusion injury","authors":"Xingzhen Liu ,&nbsp;Jia Wang ,&nbsp;Kangping Shen ,&nbsp;Wenjie Jin","doi":"10.1016/j.mad.2024.112000","DOIUrl":"10.1016/j.mad.2024.112000","url":null,"abstract":"<div><h3>Objection</h3><div>Spinal cord injury (SCI)-induced hindlimb dysfunction affects the physical and mental health of patients. There is growing evidence suggesting that the recovery capacity of elderly SCI patients is poorer than that of young individuals. However, the specific molecular mechanisms remain unclear.</div></div><div><h3>Methods</h3><div>RNA expression profiles of SCI samples were collected from the GEO database, and key genes involved in the progression of SCI were identified by the limma package in R software. A diagnostic model based on SCIDEG was constructed using LASSO regression analysis. Subsequently, correlation analysis was conducted to identify biological pathways influenced by the key genes. Furthermore, SCI animal models were established in different age groups to examine the expression of relevant genes and verify the molecular mechanism of p53/HIF-1α axis.</div></div><div><h3>Results</h3><div>We initially identified 34 ischemia-hypoxia-related genes potentially involved in the progression of SCI. Subsequently, we constructed a diagnostic model based on SCIDEGs using LASSO regression analysis. This model highlighted 9 key genes (<em>TP53</em>, <em>SFTPA1</em>, <em>MASP2</em>, <em>KRT14</em>, <em>IL9</em>, <em>HIF1A</em>, <em>HGFAC</em>, <em>FUT7</em>, and <em>ALPP</em>), which demonstrated high diagnostic accuracy in both the training set (AUC=1) and the validation set (AUC=0.855). Further cross-analysis with ischemia-reperfusion-related datasets confirmed the involvement of <em>HIF1A</em> and <em>TP53</em>. We also observed significant enrichment of <em>HIF1A</em> in organoids composed of mature neurons, which induced neuronal damage. In subsequent spinal cord injury animal models of different age groups, we found that HIF-1α expression was downregulated in the spinal cord tissues of elderly animals. Additionally, we discovered that TP53 activation induces cellular senescence in aging neurons and suppresses HIF-1α expression and autophagy levels within these cells.</div></div><div><h3>Conclusion</h3><div>In summary, our study suggests that the p53/HIF-1α signaling pathway plays a critical role in regulating neuronal aging and autophagy in the pathogenesis of SCI. Importantly, HIF-1α may represent a promising therapeutic target for SCI treatment.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"222 ","pages":"Article 112000"},"PeriodicalIF":5.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623555","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}

{"title":"Differential Plin5 response to high-fat diet in cardiomyocytes isolated from young and aged mice","authors":"Patricia Baumgarten ,&nbsp;Tobias Jung ,&nbsp;Christiane Ott ,&nbsp;Tilman Grune","doi":"10.1016/j.mad.2024.112004","DOIUrl":"10.1016/j.mad.2024.112004","url":null,"abstract":"<div><div>This study investigates the differences in the heart response to an 8-week high-fat diet between young and aged mice. Isolated cardiomyocytes reveal a significant lower level in the lipid droplet-associated protein Plin5 in aged mice. High-fat diet, however, leads to an induction of Plin5 in aged mice and a low-response of lipid metabolism, whereas in cardiomyocytes from young animals the Plin5 level was largely unaffected by high-fat diet whereas several lipid metabolizing enzymes were induced. Therefore, the high-fat diet induced lipid droplet accumulation is more pronounced in cardiomyocytes isolated from aged animals.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"222 ","pages":"Article 112004"},"PeriodicalIF":5.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605239","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}

{"title":"The abundance change of age-regulated secreted proteins affects lifespan of C. elegans","authors":"Prasun Kumar Bhunia ,&nbsp;Vishwajeet Raj ,&nbsp;Prasad Kasturi","doi":"10.1016/j.mad.2024.112003","DOIUrl":"10.1016/j.mad.2024.112003","url":null,"abstract":"<div><div>Proteome integrity is vital for survival and failure to maintain it results in uncontrolled protein abundances, misfolding and aggregation which cause proteotoxicity. In multicellular organisms, proteotoxic stress is communicated among tissues to maintain proteome integrity for organismal stress resistance and survival. However, the nature of these signalling molecules and their regulation in extracellular space is largely unknown. Secreted proteins are induced in response to various stresses and aging, indicating their roles in inter-tissue communication. To study the fates of age-regulated proteins with potential localization to extracellular, we analysed publicly available age-related proteome data of <em>C. elegans</em>. We found that abundance of majority of the proteins with signal peptides (SP) increases with age, which might result in their supersaturation and subsequent aggregation. Intriguingly, these changes are differentially regulated in the lifespan mutants. A subset of these SP proteins is also found in the cargo of extracellular vesicles. Many of these proteins are novel and functionally uncharacterized. Reducing levels of a few extracellular proteins results in increasing lifespan. This suggests that uncontrolled levels of extracellular proteins might disturb proteostasis and limit the lifespan. Overall, our findings suggest that the age-induced secreted proteins might be the potential candidates to be considered as biomarkers or for mitigating age-related pathological conditions.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"222 ","pages":"Article 112003"},"PeriodicalIF":5.3,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591124","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}

{"title":"Convergence between brain aging and Alzheimer’s disease: Focus on mitochondria","authors":"Salvatore Vaiasicca ,&nbsp;Marta Balietti ,&nbsp;Lisa Bevilacqua ,&nbsp;Belinda Giorgetti ,&nbsp;Tiziana Casoli","doi":"10.1016/j.mad.2024.112001","DOIUrl":"10.1016/j.mad.2024.112001","url":null,"abstract":"<div><div>Alzheimer's disease (AD) accounts for the majority of dementia cases, with aging being the primary risk factor for developing this neurodegenerative condition. Aging and AD share several characteristics, including the formation of amyloid plaques and neurofibrillary tangles, synaptic loss, and neuroinflammation. This overlap suggests that mechanisms driving the aging process might also promote AD; however, the underlying processes are not yet fully understood. In this narrative review, we will focus on the role of mitochondria, not only as the \"powerhouse of the cell\", but also in programmed cell death, immune response, macromolecular synthesis, and calcium regulation. We will explore both the common changes between aging and AD and the differences between them. Additionally, we will provide an overview of interventions aimed at maintaining mitochondrial function in an attempt to slow the progression of AD. This will include a discussion of antioxidant molecules, factors that trigger mitochondrial biogenesis, compounds capable of restoring the fission/fusion balance, and a particular focus on recent techniques for mitochondrial DNA gene therapy.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"222 ","pages":"Article 112001"},"PeriodicalIF":5.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569117","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}

{"title":"Design of the VOILA-intervention study: A 12-week nutrition and resistance exercise intervention in metabolic or mobility compromised Dutch older adults and the response on immune-metabolic, gut and muscle health parameters","authors":"C.S. Kramer ,&nbsp;A. Monsegue ,&nbsp;J. Morwani-Mangnani ,&nbsp;P. Grootswagers ,&nbsp;M. Beekman ,&nbsp;P.E. Slagboom ,&nbsp;L.B. Verdijk ,&nbsp;L.C.P.G.M. de Groot","doi":"10.1016/j.mad.2024.112002","DOIUrl":"10.1016/j.mad.2024.112002","url":null,"abstract":"<div><h3>Background</h3><div>Exercise and nutrition interventions can slow ageing-induced decline in physiology. However, effects are heterogeneous and usually studied separately per outcome domain. In the VOILA study, we simultaneously study various health outcomes relevant for older adults and the inter-individual heterogeneity in response to a lifestyle intervention.</div></div><div><h3>Methods</h3><div>VOILA is a 12-week lifestyle intervention in 3 groups of older adults (≥60 years), with compromised mobility (n=50), compromised metabolic health (n=50), or recovering from total knee replacement (TKR, n=70, of which 20 randomized to standard care only). The intervention includes high-intensity resistance exercise training thrice weekly, nutritional counselling, and nutritional supplements every morning and evening (including 20–25 g whey protein and (evening only) 5.5 g Biotis™ GOS). We measure immune-metabolic, gut health, muscle mass and physical functioning at baseline and after completion of the intervention/standard care. An additional reference group of healthy older adults (n=50) will undergo baseline measurements only.</div></div><div><h3>Discussion</h3><div>Improvements in various physiological systems are expected, but with differences between groups/individuals. This study will provide insights into how the physiological state of older adults influences the extent of lifestyle-induced health improvements to create better tailored interventions to attenuate biological ageing and improve the health span of subgroups and individuals.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"222 ","pages":"Article 112002"},"PeriodicalIF":5.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142555052","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}

{"title":"Challenges of infectious diseases in older adults: From immunosenescence and inflammaging through antibiotic resistance to management strategies","authors":"Francesca Mancinetti ,&nbsp;Anna Marinelli ,&nbsp;Virginia Boccardi ,&nbsp;Patrizia Mecocci","doi":"10.1016/j.mad.2024.111998","DOIUrl":"10.1016/j.mad.2024.111998","url":null,"abstract":"<div><div>Infectious diseases in older adults present a significant challenge to the healthcare system, marked by increased morbidity, mortality, and rising costs of care. Age-related changes (ARCs) in the immune system, including immunosenescence and inflammaging, contribute to heightened susceptibility to severe infections and reduced vaccine responsiveness. Additionally, alterations in the normal microbial flora due to aging and factors such as antibiotic therapy predispose older individuals to infections and age-related diseases. Changes in body composition also affect the pharmacokinetics and pharmacodynamics of drugs, complicating the management of antibiotics and leading to potential overdoses, adverse drug reactions, or underdoses that foster antibiotic resistance. The inappropriate use of antibiotics has exacerbated the emergence of multidrug-resistant pathogens, posing a critical global concern. This narrative review provides an overview of immunosenescence and inflammaging and focuses on three major infectious diseases affecting older adults: bacterial pneumonia, urinary tract infections, and Clostridium difficile infections. Through this exploration, we aim to highlight the need for targeted approaches in managing infectious diseases in the aging population.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"222 ","pages":"Article 111998"},"PeriodicalIF":5.3,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503540","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}

{"title":"Impact of senescence cell signature in patients with non-small cell carcinoma and melanoma receiving PD-L1/PD-1 inhibitors","authors":"Young Wha Koh ,&nbsp;Jae-Ho Han ,&nbsp;Seokjin Haam ,&nbsp;Hyun Woo Lee","doi":"10.1016/j.mad.2024.111999","DOIUrl":"10.1016/j.mad.2024.111999","url":null,"abstract":"<div><div>Tumor cell senescence plays a crucial role in tumor immunity. We investigated whether the senescent cell signature (SCS) could predict prognosis in non-small cell carcinoma (NSCLC) and melanoma datasets treated with PD-L1/PD-1 inhibitors. Patients with high SCS expression exhibited elevated levels of interferon-gamma and T cell-inflamed signatures in three lung adenocarcinomas (LUAD), two squamous cell carcinoma (LUSC) and three melanoma datasets. The high SCS group was associated with PD-L1-related pathways such as IL6/JAK/STAT3 and TNF-alpha signaling via NF-kB in LUAD, LUSC, and melanoma datasets. A positive correlation was observed between several immune checkpoint markers and the SCS, indicating an immunosuppressive state in LUAD, LUSC and melanoma datasets. In patients treated with PD-1/PD-L1 inhibitors, a higher SCS was associated with a better prognosis, and a positive correlation between SCS and PD-L1 was observed in six independent NSCLC and three independent melanoma datasets. We used the LASSO Cox regression model to build a risk model focusing on the SCS genes that particularly predict prognosis. We confirmed that the model accurately predicts prognosis. However, the senescent immunohistochemical markers p16 and p21 could predict the response to PD-1/PD-L1 inhibitors in patients with LUSC and melanoma but not in patients with LUAD. SCS could serve as a valuable biomarker to complement PD-L1 expression in patients receiving PD-L1/PD-1 inhibitors.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"222 ","pages":"Article 111999"},"PeriodicalIF":5.3,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469475","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}