Mechanisms of Ageing and Development最新文献_第7页

Differential Plin5 response to high-fat diet in cardiomyocytes isolated from young and aged mice 从年轻小鼠和老龄小鼠分离的心肌细胞对高脂肪饮食的不同 Plin5 反应。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-11-06 DOI: 10.1016/j.mad.2024.112004

Patricia Baumgarten , Tobias Jung , Christiane Ott , Tilman Grune

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The abundance change of age-regulated secreted proteins affects lifespan of C. elegans 年龄调控分泌蛋白的丰度变化影响秀丽隐杆线虫的寿命

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-11-05 DOI: 10.1016/j.mad.2024.112003

Prasun Kumar Bhunia , Vishwajeet Raj , Prasad Kasturi

{"title":"The abundance change of age-regulated secreted proteins affects lifespan of C. elegans","authors":"Prasun Kumar Bhunia , Vishwajeet Raj , 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}

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Convergence between brain aging and Alzheimer’s disease: Focus on mitochondria 大脑老化与阿尔茨海默氏症之间的趋同性：关注线粒体。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-10-28 DOI: 10.1016/j.mad.2024.112001

Salvatore Vaiasicca , Marta Balietti , Lisa Bevilacqua , Belinda Giorgetti , Tiziana Casoli

{"title":"Convergence between brain aging and Alzheimer’s disease: Focus on mitochondria","authors":"Salvatore Vaiasicca , Marta Balietti , Lisa Bevilacqua , Belinda Giorgetti , 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}

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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 VOILA 干预研究的设计：对代谢或行动不便的荷兰老年人进行为期 12 周的营养和阻力运动干预，以及对免疫代谢、肠道和肌肉健康参数的影响

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-10-28 DOI: 10.1016/j.mad.2024.112002

C.S. Kramer , A. Monsegue , J. Morwani-Mangnani , P. Grootswagers , M. Beekman , P.E. Slagboom , L.B. Verdijk , L.C.P.G.M. de Groot

{"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 , A. Monsegue , J. Morwani-Mangnani , P. Grootswagers , M. Beekman , P.E. Slagboom , L.B. Verdijk , 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}

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Challenges of infectious diseases in older adults: From immunosenescence and inflammaging through antibiotic resistance to management strategies 老年人传染病的挑战：从免疫衰老和炎症到抗生素耐药性，再到管理策略。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-10-22 DOI: 10.1016/j.mad.2024.111998

Francesca Mancinetti , Anna Marinelli , Virginia Boccardi , Patrizia Mecocci

{"title":"Challenges of infectious diseases in older adults: From immunosenescence and inflammaging through antibiotic resistance to management strategies","authors":"Francesca Mancinetti , Anna Marinelli , Virginia Boccardi , 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}

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Impact of senescence cell signature in patients with non-small cell carcinoma and melanoma receiving PD-L1/PD-1 inhibitors 衰老细胞特征对接受 PD-L1/PD-1 抑制剂治疗的非小细胞癌和黑色素瘤患者的影响。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-10-18 DOI: 10.1016/j.mad.2024.111999

Young Wha Koh , Jae-Ho Han , Seokjin Haam , Hyun Woo Lee

{"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 , Jae-Ho Han , Seokjin Haam , 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}

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Deciphering Osteosarcopenia through the hallmarks of aging 从衰老的标志解密骨肉疏松症

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-10-11 DOI: 10.1016/j.mad.2024.111997

Francisca Franulic , Felipe Salech , Daniel Rivas , Gustavo Duque

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Sirtuin 3 drives sex-specific responses to age-related changes in mouse embryonic fibroblasts Sirtuin 3 驱动小鼠胚胎成纤维细胞对年龄相关变化做出性别特异性反应

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-10-11 DOI: 10.1016/j.mad.2024.111996

Ena Šimunić , Iva I. Podgorski , Marija Pinterić , Marijana Popović Hadžija , Robert Belužić , Mladen Paradžik , Lucija Dončević , Tihomir Balog , Marta Kaloper , Hansjörg Habisch , Tobias Madl , Aleksandra Korać , Sandra Sobočanec

{"title":"Sirtuin 3 drives sex-specific responses to age-related changes in mouse embryonic fibroblasts","authors":"Ena Šimunić , Iva I. Podgorski , Marija Pinterić , Marijana Popović Hadžija , Robert Belužić , Mladen Paradžik , Lucija Dončević , Tihomir Balog , Marta Kaloper , Hansjörg Habisch , Tobias Madl , Aleksandra Korać , Sandra Sobočanec","doi":"10.1016/j.mad.2024.111996","DOIUrl":"10.1016/j.mad.2024.111996","url":null,"abstract":"<div><div>The aging process is a complex phenomenon characterised by a gradual decline in physiological functions and an increased susceptibility to age-related diseases. An important factor in aging is mitochondrial dysfunction, which leads to an accumulation of cellular damage over time. Mitochondrial Sirtuin 3 (Sirt3), an important regulator of energy metabolism, plays a central role in maintaining mitochondrial function. Loss of Sirt3 can lead to reduced energy levels and an impaired ability to repair cellular damage, a hallmark of the aging process. In this study we investigated the impact of Sirt3 loss on mitochondrial function, metabolic responses and cellular aging processes in male and female mouse embryonic fibroblasts (MEF) exposed to etoposide-induced DNA damage, which is commonly associated with cellular dysfunction and senescence. We found that Sirt3 contributes to the sex-specific metabolic response to etoposide treatment. While male MEF exhibited minimal damage suggesting potential prior adaptation to stress due to Sirt3 loss, female MEF lacking Sirt3 experienced higher vulnerability to genotoxic stress, implying a pivotal role of Sirt3 in their resistance to such challenges. These findings offer potential insights into therapeutic strategies targeting Sirt3- and sex-specific signalling pathways in diseases associated with DNA damage that play a critical role in the aging process.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"222 ","pages":"Article 111996"},"PeriodicalIF":5.3,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441524","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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Fisetin as a senotherapeutic agent: Evidence and perspectives for age-related diseases 作为老年治疗剂的鱼腥草素：老年性疾病的证据与前景》。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-10-09 DOI: 10.1016/j.mad.2024.111995

Juliette Tavenier , Jan O. Nehlin , Morten Baltzer Houlind , Lene Juel Rasmussen , Tamara Tchkonia , James L. Kirkland , Ove Andersen , Line Jee Hartmann Rasmussen

{"title":"Fisetin as a senotherapeutic agent: Evidence and perspectives for age-related diseases","authors":"Juliette Tavenier , Jan O. Nehlin , Morten Baltzer Houlind , Lene Juel Rasmussen , Tamara Tchkonia , James L. Kirkland , Ove Andersen , Line Jee Hartmann Rasmussen","doi":"10.1016/j.mad.2024.111995","DOIUrl":"10.1016/j.mad.2024.111995","url":null,"abstract":"<div><div>Fisetin, a flavonoid naturally occurring in plants, fruits, and vegetables, has recently gained attention for its potential role as a senotherapeutic agent for the treatment of age-related chronic diseases. Senotherapeutics target senescent cells, which accumulate with age and disease, in both circulating immune cell populations and solid organs and tissues. Senescent cells contribute to development of many chronic diseases, primarily by eliciting systemic chronic inflammation through their senescence-associated secretory phenotype. Here, we explore whether fisetin as a senotherapeutic can eliminate senescent cells, and thereby alleviate chronic diseases, by examining current evidence from <em>in vitro</em> studies and animal models that investigate fisetin’s impact on age-related diseases, as well as from phase I/II trials in various patient populations. We discuss the application of fisetin in humans, including challenges and future directions. Our review of available data suggests that targeting senescent cells with fisetin offers a promising strategy for managing multiple chronic diseases, potentially transforming future healthcare for older and multimorbid patients. However, further studies are needed to establish the safety, pharmacokinetics, and efficacy of fisetin as a senotherapeutic, identify relevant and reliable outcome measures in human trials, optimize dosing, and better understand the possible limitations of fisetin as a senotherapeutic agent.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"222 ","pages":"Article 111995"},"PeriodicalIF":5.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391708","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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The impact of opioids on the hallmarks of ageing 阿片类药物对衰老特征的影响。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-09-24 DOI: 10.1016/j.mad.2024.111994

Ana Rita Tavares Henriques , João Pedro Silva , Félix Carvalho

{"title":"The impact of opioids on the hallmarks of ageing","authors":"Ana Rita Tavares Henriques , João Pedro Silva , Félix Carvalho","doi":"10.1016/j.mad.2024.111994","DOIUrl":"10.1016/j.mad.2024.111994","url":null,"abstract":"<div><div>Opioids rank among the most hazardous substances of abuse, leading to opioid use disorders (which greatly diminish life quality) and contributing to the highest drug-related mortality rates. Nonetheless, both the therapeutic and recreational use of opioids is escalating globally. Interestingly, chronic opioid users often exhibit signs consistent with accelerated ageing, suggesting that they likely interfere with well-characterized ageing mechanisms (e.g., telomere shortening, epigenetic changes, mitochondrial dysfunction, cellular senescence). Here, we review the most recent advances regarding the impact of opioids on well-characterized hallmarks of ageing, to ascertain a potential association between opioid use and accelerated ageing. Our findings indicate that there is accumulating evidence supporting a close association between the use of opioids and the early onset of some ageing hallmarks, namely mitochondrial dysfunction, genomic instability, or telomere shortening. However, there is still limited data available regarding how opioids specifically impact other ageing hallmarks, like nutrient sensing, cellular senescence, or loss of proteostasis. Taking into consideration the high prevalence of opioid use, strengthening the understanding of the mechanisms underlying opioids’ impact on ageing assumes utmost relevance, both in terms of improving risk assessment, as well as to help researchers and clinicians prevent or mitigate these effects in clinical settings.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"222 ","pages":"Article 111994"},"PeriodicalIF":5.3,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349662","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