Mechanisms of Ageing and Development最新文献

{"title":"Development and validation of cardiometabolic risk predictive models based on LDL oxidation and candidate geromarkers from the MARK-AGE data","authors":"Andrei Valeanu ,&nbsp;Denisa Margina ,&nbsp;Daniela Weber ,&nbsp;Wolfgang Stuetz ,&nbsp;María Moreno-Villanueva ,&nbsp;Martijn E.T. Dollé ,&nbsp;Eugène HJM Jansen ,&nbsp;Efstathios S. Gonos ,&nbsp;Jürgen Bernhardt ,&nbsp;Beatrix Grubeck-Loebenstein ,&nbsp;Birgit Weinberger ,&nbsp;Simone Fiegl ,&nbsp;Ewa Sikora ,&nbsp;Grazyna Mosieniak ,&nbsp;Olivier Toussaint ,&nbsp;Florence Debacq-Chainiaux ,&nbsp;Miriam Capri ,&nbsp;Paolo Garagnani ,&nbsp;Chiara Pirazzini ,&nbsp;Maria Giulia Bacalini ,&nbsp;Daniela Gradinaru","doi":"10.1016/j.mad.2024.111987","DOIUrl":"10.1016/j.mad.2024.111987","url":null,"abstract":"<div><p>The predictive value of the susceptibility to oxidation of LDL particles (LDLox) in cardiometabolic risk assessment is incompletely understood. The main objective of the current study was to assess its relationship with other relevant biomarkers and cardiometabolic risk factors from MARK-AGE data. A cross-sectional observational study was carried out on 1089 subjects (528 men and 561 women), aged 40–75 years old, randomly recruited age- and sex-stratified individuals from the general population. A correlation analysis exploring the relationships between LDLox and relevant biomarkers was undertaken, as well as the development and validation of several machine learning algorithms, for estimating the risk of the combined status of high blood pressure and obesity for the MARK-AGE subjects. The machine learning models yielded Area Under the Receiver Operating Characteristic Curve Score ranging 0.783–0.839 for the internal validation, while the external validation resulted in an Under the Receiver Operating Characteristic Curve Score between 0.648 and 0.787, with the variables based on LDLox reaching significant importance within the obtained predictions. The current study offers novel insights regarding the combined effects of LDL oxidation and other ageing markers on cardiometabolic risk. Future studies might be extended on larger patient cohorts, in order to obtain reproducible clinical assessment models.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"222 ","pages":"Article 111987"},"PeriodicalIF":5.3,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0047637424000873/pdfft?md5=1386a90e65cd9d45e836df338224fc15&pid=1-s2.0-S0047637424000873-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142274207","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":"Characterization of a natural model of adult mice with different rate of aging","authors":"Judith Félix ,&nbsp;Estefanía Díaz-Del Cerro ,&nbsp;Antonio Garrido ,&nbsp;Mónica De La Fuente","doi":"10.1016/j.mad.2024.111991","DOIUrl":"10.1016/j.mad.2024.111991","url":null,"abstract":"<div><p>Aging is a heterogeneous process, so individuals of the same age may be aging at a different rate. A natural model of premature aging in mice have been proposed based on the poor response to the T-maze. Those that take longer to cross the intersection are known as Prematurely Aging Mice (PAM), while those that show an exceptional response are known as Exceptional non-PAM (E-NPAM), being the rest non-PAM (NPAM). Although many aspects of PAM and E-NPAM have been described, some aspects of their brain aging have not been studied. Similarly, it is known that PAM, NPAM and E-NPAM show a different rate of aging and longevity, but the differences between these three groups in behavior, immune function and oxidative-inflammatory state are unknown. The present study aims to deepen the study of brain aging in PAM and E-NPAM, and to study the differences in behavior, immunity, and oxidative-inflammatory state of peritoneal leukocytes between PAM, NPAM and E-NPAM. Results show deteriorated brains in PAM. Moreover, NPAM show an oxidative state similar to E-NPAM, an anxiety similar to PAM, and an intermediate immunity and lifespan between PAM and E-NPAM. In conclusion, immune function seems to be more associated with the longevity achieved.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"222 ","pages":"Article 111991"},"PeriodicalIF":5.3,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0047637424000915/pdfft?md5=0f665552aebe743365069cd5591a4e16&pid=1-s2.0-S0047637424000915-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142239885","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":"Mitigating the effects of time in the heart and liver: The variable effects of short- and long-term caloric restriction","authors":"Milica Prvulovic ,&nbsp;Sladjan Pavlovic ,&nbsp;Slavica Borkovic Mitic ,&nbsp;Valentina Simeunovic ,&nbsp;Andjela Vukojevic ,&nbsp;Smilja Todorovic ,&nbsp;Aleksandra Mladenovic","doi":"10.1016/j.mad.2024.111992","DOIUrl":"10.1016/j.mad.2024.111992","url":null,"abstract":"<div><p>Caloric restriction (CR) is known for its anti-aging benefits, partly due to reduced oxidative stress and enhanced antioxidant defense. However, CR outcomes vary based on its intensity, timing, and duration. This study explored CR's effects on antioxidant activity in the heart and liver of male Wistar rats during aging. We investigated two CR paradigms: long-term CR (LTCR), started early in life, and short-term CR (STCR), initiated in middle or old age for 3 months. Contrary to previous findings of short-term CR deleterious effects of on the nervous system, our results revealed increased levels of key antioxidants after STCR. More specifically, we found an increase in GSH-Px and GSH under STCR that was particularly pronounced in the liver, while an increase in CAT and GR activities was observed in the heart of the STCR groups. Catalase was characterized as an enzyme particularly responsive to CR, as its activity was also increased in both the liver and heart after long-term caloric restriction. Our results highlight a significant tissue-specific response to CR and contribute to our understanding of the dynamic effects of CR, which in turn has implications for refining its therapeutic potential in combating age-related decline.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"222 ","pages":"Article 111992"},"PeriodicalIF":5.3,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142274208","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":"Adipose tissue senescence: Biological changes, hallmarks and therapeutic approaches","authors":"Yajuan Zhang ,&nbsp;Yaoyao Jiang ,&nbsp;Xiaoyue Yang ,&nbsp;Yumei Huang ,&nbsp;An Pan ,&nbsp;Yunfei Liao","doi":"10.1016/j.mad.2024.111988","DOIUrl":"10.1016/j.mad.2024.111988","url":null,"abstract":"<div><p>Adipose tissue (AT), the largest energy storage reservoir and endocrine organ, plays a crucial role in regulating systemic energy metabolism. As one of the most vulnerable tissues during aging, the plasticity of AT is impaired. With age, AT undergoes redistribution, characterized by expansion of visceral adipose tissue (VAT) and reduction of peripheral subcutaneous adipose tissue (SAT). Additionally, age-related changes in AT include reduced adipogenesis of white adipocytes, decreased proliferation and differentiation capacity of mesenchymal stromal/stem cells (MSCs), diminished thermogenic capacity in brown/beige adipocytes, and dysregulation of immune cells. Specific and sensitive hallmarks enable the monitoring and evaluation of the biological changes associated with aging. In this study, we have innovatively proposed seven characteristic hallmarks of AT senescence, including telomere attrition, epigenetic alterations, genomic instability, mitochondrial dysfunction, disabled macroautophagy, cellular senescence, and chronic inflammation, which are intricately interconnected and mutually regulated. Finally, we discussed anti-aging strategies targeting AT, offering insights into mitigating or delaying metabolic disturbances caused by AT senescence.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"222 ","pages":"Article 111988"},"PeriodicalIF":5.3,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142239883","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":"Deletion of stimulator of interferons genes aggravated cardiac dysfunction in physiological aged mice","authors":"Diansa Gao ,&nbsp;Boying Zhao ,&nbsp;Jiang Yu ,&nbsp;Xiaorong Li ,&nbsp;Ding Yang ,&nbsp;Yuan Luo ,&nbsp;Yong Xia ,&nbsp;Xiongwei Cai ,&nbsp;Yongzheng Guo","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":"222 ","pages":"Article 111978"},"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}

{"title":"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]","authors":"Miriam Carella ,&nbsp;Daniele Magro ,&nbsp;Letizia Scola ,&nbsp;Calogera Pisano ,&nbsp;Eugenia Guida ,&nbsp;Francesco Gervasi ,&nbsp;Caterina Giambanco ,&nbsp;Tommaso Silvano Aronica ,&nbsp;Giacomo Frati ,&nbsp;Carmela Rita Balistreri","doi":"10.1016/j.mad.2024.111977","DOIUrl":"10.1016/j.mad.2024.111977","url":null,"abstract":"","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"221 ","pages":"Article 111977"},"PeriodicalIF":5.3,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0047637424000770/pdfft?md5=6f695f5a052874a0423c3724e9170576&pid=1-s2.0-S0047637424000770-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976067","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":"Senescence of skeletal stem cells and their contribution to age-related bone loss","authors":"Eva M. Wölfel ,&nbsp;Paula Fernandez-Guerra ,&nbsp;Mikkel Ørnfeldt Nørgård ,&nbsp;Shakespeare Jeromdesella ,&nbsp;Pernille Kirkegaard Kjær ,&nbsp;Anna Sofie Elkjær ,&nbsp;Moustapha Kassem ,&nbsp;Florence Figeac","doi":"10.1016/j.mad.2024.111976","DOIUrl":"10.1016/j.mad.2024.111976","url":null,"abstract":"<div><p>Human aging is linked to bone loss, resulting in bone fragility and an increased risk of fractures. This is primarily due to an age-related decline in the function of bone-forming osteoblastic cells and accelerated cellular senescence within the bone microenvironment. Here, we provide a detailed discussion of the hypothesis that age-related defective bone formation is caused by senescence of skeletal stem cells, as they are the main source of bone forming osteoblastic cells and influence the composition of bone microenvironment. Furthermore, this review discusses potential strategies to target cellular senescence as an emerging approach to treat age-related bone loss.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"221 ","pages":"Article 111976"},"PeriodicalIF":5.3,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0047637424000769/pdfft?md5=ac84534fac5bff3ba30f6d6af4a6a915&pid=1-s2.0-S0047637424000769-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902143","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 emerging importance of lymphangiogenesis in aging and aging-associated diseases","authors":"Rui-Cheng Ji","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":"221 ","pages":"Article 111975"},"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}

{"title":"Potential protein biomarkers in saliva for detection of frailty syndrome by targeted proteomics","authors":"Alfonssina Niebla-Cárdenas ,&nbsp;Nallely Bueno-Hernández ,&nbsp;Angela-Patricia Hernández ,&nbsp;Manuel Fuentes ,&nbsp;Roberto Méndez-Sánchez ,&nbsp;Eva María Arroyo-Anlló ,&nbsp;Irene Orera ,&nbsp;Giuseppe Lattanzio ,&nbsp;Pablo Juanes-Velasco ,&nbsp;Carlota Arias-Hidalgo ,&nbsp;Ana Silvia Puente-González","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":"221 ","pages":"Article 111974"},"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}

{"title":"Sestrin2 plays a protective role in age-related hearing loss by inhibiting NLRP3-inflammasome activity","authors":"Liting Zheng ,&nbsp;Menghua Li ,&nbsp;Yalan Li ,&nbsp;Liyuan Wu ,&nbsp;Konduru Naveena ,&nbsp;Mengzhu Zheng ,&nbsp;Zhanqun Yang ,&nbsp;Yong Pan ,&nbsp;Yunshi Zhang ,&nbsp;Shujin Chen ,&nbsp;Yuehua Qiao ,&nbsp;Yice Xu ,&nbsp;Long Chen ,&nbsp;Xi Shi","doi":"10.1016/j.mad.2024.111964","DOIUrl":"10.1016/j.mad.2024.111964","url":null,"abstract":"<div><p>Age-related hearing loss (ARHL) is an auditory disease characterized by gradual loss of high-frequency hearing sensitivity. Excessive reactive oxygen species trigger NLRP3-inflammasome activation that may be crucial for ARHL pathogenesis. The antioxidant factor Sestrin2 (SESN2) has been reported to be involved in the remission of oxidative stress and ARHL. However, the mechanism by which SESN2 protects auditory cells in the aging mouse cochlea remains unknown. Here, we observed that ectopic overexpression of SESN2 delayed ARHL, whereas SESN2 knockdown accelerated it. Importantly, we elucidated that SESN2 exerts a hearing-protective effect by inhibiting the production of NLRP3 by acting as a mitophagy agonist. Our study proposes a new theoretical basis for SESN2 prevention of ARHL and provides a novel therapeutic strategy for maintaining SESN2 activity in the aging cochlea.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"221 ","pages":"Article 111964"},"PeriodicalIF":5.3,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633872","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}