Mechanisms of Ageing and Development最新文献

{"title":"Retraction notice to “A feasibility study of the combination of intranasal insulin with dulaglutide for cognition in older adults with metabolic syndrome at high dementia risk- Study rationale and design” [Mech. Ageing Dev. 213 (2023) 111825]","authors":"Tal Davidy , Iscka Yore , Tali Cukierman-Yaffe , Ramit Ravona-Springer , Abigail Livny , Orit H. Lesman-Segev , Yossi Azuri , Owen Carmichael , Dimitrios Kapogiannis , Henrik Zetterberg , HungMo Lin , Mary Sano , Michal Schnaider Beeri","doi":"10.1016/j.mad.2024.111937","DOIUrl":"10.1016/j.mad.2024.111937","url":null,"abstract":"","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"219 ","pages":"Article 111937"},"PeriodicalIF":5.3,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S004763742400037X/pdfft?md5=8486f904a09f892f59712b3c078b2f98&pid=1-s2.0-S004763742400037X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140859346","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":"SuperAgers and centenarians, dynamics of healthy ageing with cognitive resilience","authors":"Md Ariful Islam ,&nbsp;Ujala Sehar ,&nbsp;Omme Fatema Sultana ,&nbsp;Upasana Mukherjee ,&nbsp;Malcolm Brownell ,&nbsp;Sudhir Kshirsagar ,&nbsp;P. Hemachandra Reddy","doi":"10.1016/j.mad.2024.111936","DOIUrl":"https://doi.org/10.1016/j.mad.2024.111936","url":null,"abstract":"<div><p>Graceful healthy ageing and extended longevity is the most desired goal for human race. The process of ageing is inevitable and has a profound impact on the gradual deterioration of our physiology and health since it triggers the onset of many chronic conditions like dementia, osteoporosis, diabetes, arthritis, cancer, and cardiovascular disease. However, some people who lived/live more than 100 years called ‘Centenarians” and how do they achieve their extended lifespans are not completely understood. Studying these unknown factors of longevity is important not only to establish a longer human lifespan but also to manage and treat people with shortened lifespans suffering from age-related morbidities. Furthermore, older adults who maintain strong cognitive function are referred to as \"SuperAgers\" and may be resistant to risk factors linked to cognitive decline. Investigating the mechanisms underlying their cognitive resilience may contribute to the development of therapeutic strategies that support the preservation of cognitive function as people age. The key to a long, physically, and cognitively healthy life has been a mystery to scientists for ages. Developments in the medical sciences helps us to a better understanding of human physiological function and greater access to medical care has led us to an increase in life expectancy. Moreover, inheriting favorable genetic traits and adopting a healthy lifestyle play pivotal roles in promoting longer and healthier lives. Engaging in regular physical activity, maintaining a balanced diet, and avoiding harmful habits such as smoking contribute to overall well-being. The synergy between positive lifestyle choices, access to education, socio-economic factors, environmental determinants and genetic supremacy enhances the potential for a longer and healthier life. Our article aims to examine the factors associated with healthy ageing, particularly focusing on cognitive health in centenarians. We will also be discussing different aspects of ageing including genomic instability, metabolic burden, oxidative stress and inflammation, mitochondrial dysfunction, cellular senescence, immunosenescence, and sarcopenia.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"219 ","pages":"Article 111936"},"PeriodicalIF":5.3,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140641300","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":"Effect of in vivo culture conditions on the proliferation and differentiation of rat adipose-derived stromal cells","authors":"Chao Wang ,&nbsp;Tian Xie ,&nbsp;Xiaoming Li ,&nbsp;Xue Lu ,&nbsp;Changxue Xiao ,&nbsp;Ping Liu ,&nbsp;Feng Xu ,&nbsp;Bo Zhang","doi":"10.1016/j.mad.2024.111935","DOIUrl":"10.1016/j.mad.2024.111935","url":null,"abstract":"<div><p>Adipose-derived stromal cells (ADSCs) are promising stem cell sources for tissue engineering and cell-based therapy. However, long-term <em>in vitro</em> expansion of ADSCs impedes stemness maintenance, which is partly attributed to deprivation of their original microenvironment. Incompetent cells limit the therapeutic effects of ADSC-based clinical strategies. Therefore, reconstructing a more physiologically and physically relevant niche is an ideal strategy to address this issue and therefore facilitates the extensive application of ADSCs. Here, we transplanted separated ADSCs into local subcutaneous adipose tissues of nude mice as an <em>in vivo</em> cell culture model. We found that transplanted ADSCs maintained their primitive morphology and showed improved proliferation and delayed senescence compared to those of cells cultured in an incubator. Significantly increased expression of stemness-related markers and multilineage differentiation abilities were further observed in <em>in vivo</em> cultured ADSCs. Finally, sequencing revealed that genes whose expression differed between ADSCs obtained under <em>in vivo</em> and <em>in vitro</em> conditions were mainly located in the extracellular matrix and extracellular space and that these genes participate in regulating transcription and protein synthesis. Moreover, we found that an Egr1 signaling pathway might exert a crucial impact on controlling stemness properties. Our findings might collectively pave the way for ADSC-based applications.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"219 ","pages":"Article 111935"},"PeriodicalIF":5.3,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140761275","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":"Plasma cfDNA abundance as a prognostic biomarker for higher risk of death in geriatric cardiovascular patients","authors":"Maurizio Cardelli ,&nbsp;Francesca Marchegiani ,&nbsp;Pierpaolo Stripoli ,&nbsp;Francesco Piacenza ,&nbsp;Rina Recchioni ,&nbsp;Mirko Di Rosa ,&nbsp;Robertina Giacconi ,&nbsp;Marco Malavolta ,&nbsp;Roberta Galeazzi ,&nbsp;Beatrice Arosio ,&nbsp;Fiammetta Cafarelli ,&nbsp;Francesco Spannella ,&nbsp;Antonio Cherubini ,&nbsp;Fabrizia Lattanzio ,&nbsp;Fabiola Olivieri","doi":"10.1016/j.mad.2024.111934","DOIUrl":"https://doi.org/10.1016/j.mad.2024.111934","url":null,"abstract":"<div><p>The management of geriatric cardiovascular disease (CVD) patients with multimorbidity remains challenging and could potentially be improved by integrating clinical data with innovative prognostic biomarkers. In this context, the analysis of circulating analytes, including cell-free DNA (cfDNA), appears particularly promising. Here, we investigated circulating cfDNA (measured through the quantification of 247 bp and 115 bp Alu genomic fragments) in a cohort of 244 geriatric CVD patients with multimorbidity hospitalised for acute CVD or non-CVD events. Survival analysis showed a direct association between Alu 247 cfDNA abundance and risk of death, particularly evident in the first six months after admission for acute CVD events. Higher plasma cfDNA concentration was associated with mortality in the same period of time. The cfDNA integrity (Alu 247/115), although not associated with outcome, appeared to be useful in discriminating patients in whom Alu 247 cfDNA abundance is most effective as a prognostic biomarker. The cfDNA parameters were associated with several biochemical markers of inflammation and myocardial damage. In conclusion, an increase in plasma cfDNA abundance at hospital admission is indicative of a higher risk of death in geriatric CVD patients, especially after acute CVD events, and its analysis may be potentially useful for risk stratification.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"219 ","pages":"Article 111934"},"PeriodicalIF":5.3,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140550958","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 Seipin in cholesterol mediated lipid droplet maturation; status of endoplasmic reticulum stress and lipophagy","authors":"Tugce Demirel-Yalciner ,&nbsp;Bengu Cetinkaya ,&nbsp;Erdi Sozen ,&nbsp;Nesrin Kartal Ozer","doi":"10.1016/j.mad.2024.111933","DOIUrl":"https://doi.org/10.1016/j.mad.2024.111933","url":null,"abstract":"<div><p>The global prevalence of nonalcoholic fatty liver disease (NAFLD) defined by the increased number of lipid droplets (LDs) in hepatocytes, have risen continuously in parallel with the obesity. LDs and related proteins are known to affect cellular metabolism and signaling. Seipin, one of the most important LD-related proteins, plays a critical role in LD biogenesis. Although the role of adipose tissue-specific Seipin silencing is known, hepatocyte-specific silencing upon cholesterol-mediated lipid accumulation has not been investigated. In our study, we investigated the effect of Seipin on endoplasmic reticulum (ER) stress and lipophagy in cholesterol accumulated mouse hepatocyte cells. In this direction, cholesterol accumulation was induced by cholesterol-containing liposome, while Seipin mRNA and protein levels were reduced by siRNA. Our findings show that cholesterol containing liposome administration in hepatocytes increases both Seipin protein and number of large LDs. However Seipin silencing reduced the increase of cholesterol mediated large LDs and Glucose-regulated protein 78 (GRP78) mRNA. Additionally, lysosome-LD colocalization increased only in cells treated with cholesterol containing liposome, while the siRNA against Seipin did not lead any significant difference. According to our findings, we hypothesize that Seipin silencing in hepatocytes reduced cholesterol mediated LD maturation as well as GRP78 levels, but not lipophagy.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"219 ","pages":"Article 111933"},"PeriodicalIF":5.3,"publicationDate":"2024-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140547045","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":"Renal lipid accumulation and aging linked to tubular cells injury via ANGPTL4","authors":"Xiaojun Wang ,&nbsp;Hung-chen Chang ,&nbsp;Xuchao Gu ,&nbsp;Wanlin Han ,&nbsp;Shihang Mao ,&nbsp;Lili Lu ,&nbsp;Shuai Jiang ,&nbsp;Haiyong Ding ,&nbsp;Shisheng Han ,&nbsp;Xinkai Qu ,&nbsp;Zhijun Bao","doi":"10.1016/j.mad.2024.111932","DOIUrl":"https://doi.org/10.1016/j.mad.2024.111932","url":null,"abstract":"<div><p>Renal tubular epithelial cells are vulnerable to stress-induced damage, including excessive lipid accumulation and aging, with ANGPTL4 potentially playing a crucial bridging role between these factors. In this study, RNA-sequencing was used to identify a marked increase in ANGPTL4 expression in kidneys of diet-induced obese and aging mice. Overexpression and knockout of ANGPTL4 in renal tubular epithelial cells (HK-2) was used to investigate the underlying mechanism. Subsequently, ANGPTL4 expression in plasma and kidney tissues of normal young controls and elderly individuals was analyzed using ELISA and immunohistochemical techniques. RNA sequencing results showed that ANGPTL4 expression was significantly upregulated in the kidney tissue of diet-induced obesity and aging mice. In vitro experiments demonstrated that overexpression of ANGPTL4 in HK-2 cells led to increased lipid deposition and senescence. Conversely, the absence of ANGPTL4 appears to alleviate the impact of free fatty acids (FFA) on aging in HK-2 cells. Additionally, aging HK-2 cells exhibited elevated ANGPTL4 expression, and stress response markers associated with cell cycle arrest. Furthermore, our clinical evidence revealed dysregulation of ANGPTL4 expression in serum and kidney tissue samples obtained from elderly individuals compared to young subjects. Our study findings indicate a potential association between ANGPTL4 and age-related metabolic disorders, as well as injury to renal tubular epithelial cells. This suggests that targeting ANGPTL4 could be a viable strategy for the clinical treatment of renal aging.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"219 ","pages":"Article 111932"},"PeriodicalIF":5.3,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140547046","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 the land of not-unhappiness: On the state-of-the-art of targeting aging and age-related diseases by biomedical research","authors":"Eirini Klinaki ,&nbsp;Mikolaj Ogrodnik","doi":"10.1016/j.mad.2024.111929","DOIUrl":"10.1016/j.mad.2024.111929","url":null,"abstract":"<div><p>The concept of the Land of Not-Unhappiness refers to the potential achievement of eliminating the pathologies of the aging process. To inform of how close we are to settling in the land, we summarize and review the achievements of research on anti-aging interventions over the last hundred years with a specific focus on strategies that slow down metabolism, compensate for aging-related losses, and target a broad range of age-related diseases. We critically evaluate the existing interventions labeled as \"anti-aging,\" such as calorie restriction, exercise, stem cell administration, and senolytics, to provide a down-to-earth evaluation of their current applicability in counteracting aging. Throughout the text, we have maintained a light tone to make it accessible to non-experts in biogerontology, and provide a broad overview for those considering conducting studies, research, or seeking to understand the scientific basis of anti-aging medicine.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"219 ","pages":"Article 111929"},"PeriodicalIF":5.3,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140336197","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":"Molecular mechanisms implicated in protein changes in the Alzheimer’s disease human hippocampus","authors":"Hai Duc Nguyen ,&nbsp;Woong-Ki Kim ,&nbsp;Huong Huong Vu","doi":"10.1016/j.mad.2024.111930","DOIUrl":"10.1016/j.mad.2024.111930","url":null,"abstract":"<div><p>This study aimed to elucidate the specific biochemical pathways linked to changes in proteins in the Alzheimer's disease (AD) human hippocampus. Our data demonstrate a constant rise in the expression of four proteins (VGF, GFAP, HSPB1, and APP) across all eleven studies. Notably, UBC was the most centrally involved and had increased expression in the hippocampus tissue of individuals with AD. Modified proteins in the hippocampal tissue were found to activate the innate immune system and disrupt communication across chemical synapses. Four hub proteins (CD44, APP, ITGB2, and APOE) are connected to amyloid plaques, whereas two hub proteins (RPL24 and RPS23) are related to neurofibrillary tangles (NFTs). The presence of modified proteins was discovered to trigger the activation of microglia and decrease the functioning of ribosomes and mitochondria in the hippocampus. Three significant microRNAs (hsa-miR-106b-5p, hsa-miR-17–5p, and hsa-miR-16–5p) and transcription factors (MYT1L, PIN1, and CSRNP3) have been discovered to improve our understanding of the alterations in proteins within the hippocampal tissues that lead to the progression of AD. These findings establish a path for possible treatments for AD to employ therapeutic strategies that specifically focus on the proteins or processes linked to the illness.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"219 ","pages":"Article 111930"},"PeriodicalIF":5.3,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0047637424000307/pdfft?md5=ef967dca271792cddf413546b3910dd8&pid=1-s2.0-S0047637424000307-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140329940","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":"Mitochondria-targeted esculetin and metformin delay endothelial senescence by promoting fatty acid β-oxidation: Relevance in age-associated atherosclerosis","authors":"Sriravali Pulipaka ,&nbsp;Hridya Chempon ,&nbsp;Gajalakshmi Singuru ,&nbsp;Shashikanta Sahoo ,&nbsp;Altab Shaikh ,&nbsp;Sunita Kumari ,&nbsp;Rajamannar Thennati ,&nbsp;Srigiridhar Kotamraju","doi":"10.1016/j.mad.2024.111931","DOIUrl":"https://doi.org/10.1016/j.mad.2024.111931","url":null,"abstract":"<div><p>Impaired mitochondrial fatty acid β<strong>-</strong>oxidation (FAO) plays a role in the onset of several age-associated diseases, including atherosclerosis. In the current work, we investigated the efficacies of mitochondria-targeted esculetin (Mito-Esc) and metformin in enhancing FAO in human aortic endothelial cells (HAECs), and its relevance in the delay of cellular senescence and age-associated atherosclerotic plaque formation in <em>Apoe</em>^-/- mice. Chronic culturing of HAECs with either Mito-Esc or metformin increased oxygen consumption rates (OCR), and caused delay in senescence features. Conversely, etomoxir (CPT1 inhibitor) reversed Mito-Esc- and metformin-induced OCR, and caused premature endothelial senescence. Interestingly, Mito-Esc, unlike metformin, in the presence of etomoxir failed to preserve OCR. Thereby, underscoring Mito-Esc’s exclusive reliance on FAO as an energy source. Mechanistically, chronic culturing of HAECs with either Mito-Esc or metformin led to AMPK activation, increased CPT1 activity, and acetyl-CoA levels along with a concomitant reduction in malonyl-CoA levels, and lipid accumulation. Similar results were observed in Apoe^-/- mice aorta and liver tissue with a parallel reduction in age-associated atherosclerotic plaque formation and degeneration of liver with either Mito-Esc or metformin administration. Together, Mito-Esc and metformin by potentiating FAO, may have a role in the delay of cellular senescence by modulating mitochondrial function.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"219 ","pages":"Article 111931"},"PeriodicalIF":5.3,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140327914","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":"Unraveling the dual role of ADAM10: Bridging the gap between cancer and Alzheimer’s disease","authors":"Vanessa Alexandre-Silva,&nbsp;Marcia Regina Cominetti","doi":"10.1016/j.mad.2024.111928","DOIUrl":"10.1016/j.mad.2024.111928","url":null,"abstract":"<div><p>An inverse association between Alzheimer’s disease (AD) and cancer has been proposed. Patients with a cancer history have a decreased risk of developing AD, and AD patients have a reduced cancer incidence, which is not seen in vascular dementia patients. Given this association, common molecular and biological mechanisms that could explain this inverse relationship have been proposed before, such as Peptidylprolyl Cis/Trans Isomerase, NIMA-Interacting 1 (Pin1), Wingless and Int-1 (Wnt), and transformation-related protein 53 (p53)-mediated pathways, along with inflammation and oxidative stress-related proteins. A Disintegrin And Metalloprotease 10 (ADAM10) is a protease responsible for the cleavage of key AD- and cancer-related substrates, and it has inverse roles in those diseases: neuroprotective and disease-promoting, respectively. Thus, herein, we review the relevant literature linking AD and cancer and propose how ADAM10 activity might modulate the inverse association between the diseases. Understanding how this protease mediates those two conditions might raise some considerations in the ADAM10 pharmacological modulation for treating AD and cancer.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"219 ","pages":"Article 111928"},"PeriodicalIF":5.3,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140184827","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}