Mechanisms of Ageing and Development最新文献_第4页

Linking nutrition and aging: A cross-domain analysis of Mediterranean Diet Adhesion Screener components 链接营养和衰老：地中海饮食粘连筛选组件的跨域分析。

IF 5.1 3区医学

Mechanisms of Ageing and Development Pub Date : 2025-12-01 Epub Date: 2025-10-15 DOI: 10.1016/j.mad.2025.112119

Fatma Hastaoǧlu , Sonia de Pascual-Teresa

{"title":"Linking nutrition and aging: A cross-domain analysis of Mediterranean Diet Adhesion Screener components","authors":"Fatma Hastaoǧlu , Sonia de Pascual-Teresa","doi":"10.1016/j.mad.2025.112119","DOIUrl":"10.1016/j.mad.2025.112119","url":null,"abstract":"<div><div>This study explores the scientific landscape linking the Mediterranean Diet Adherence Screener (MEDAS) to aging-related health outcomes through a comprehensive bibliometric and scoping review approach. Given the increasing prevalence of chronic conditions in aging populations, diet has emerged as a modifiable factor with potential to enhance health span. The Mediterranean diet, characterized by high intake of vegetables, fruits, olive oil, and legumes, has shown promise in promoting cardiovascular, neurological, and metabolic health. MEDAS, a validated 14-item questionnaire developed within the PREDIMED study, serves as a practical tool to assess adherence to this dietary pattern. The current analysis spans literature from 2000 to 2025 and includes 203 peer-reviewed publications indexed in Web of Science. Using VOSviewer and CiteSpace software, co-occurrence maps, keyword clusters, and disease associations were visualized. Results indicate that fish, vegetables, nuts, and olive oil are the most frequently studied MEDAS components. Cardiovascular aging emerged as the most researched domain, followed by general aging and neurodegenerative conditions, while dermatological aging remains underexplored. Key themes such as cognitive decline, frailty, inflammaging, and longevity underscore the multidimensional role of MEDAS. Findings suggest that MEDAS is not only a dietary adherence measure but also a valuable instrument in preventive geriatric nutrition. Its global adaptability, simplicity, and strong predictive value make it a suitable tool for clinical and community-based nutritional strategies. This study contributes a consolidated foundation for future interdisciplinary efforts to integrate diet-based approaches into aging research and public health policy.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"228 ","pages":"Article 112119"},"PeriodicalIF":5.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Defective mitochondrial quality control in the aging of skeletal muscle 骨骼肌老化过程中线粒体质量控制缺陷。

IF 5.1 3区医学

Mechanisms of Ageing and Development Pub Date : 2025-12-01 Epub Date: 2025-09-08 DOI: 10.1016/j.mad.2025.112112

Emanuele Marzetti , Riccardo Calvani , Helio José Coelho-Junior , Francesco Landi , Anna Picca

{"title":"Defective mitochondrial quality control in the aging of skeletal muscle","authors":"Emanuele Marzetti , Riccardo Calvani , Helio José Coelho-Junior , Francesco Landi , Anna Picca","doi":"10.1016/j.mad.2025.112112","DOIUrl":"10.1016/j.mad.2025.112112","url":null,"abstract":"<div><div>Age-related skeletal muscle decline is a major contributor to frailty, functional impairment, and loss of independence in advanced age. This process is characterized by selective atrophy of type II fibers, impaired excitation–contraction coupling, and reduced regenerative capacity. Emerging evidence implicates mitochondrial dysfunction as a central mechanism in the disruption of muscle homeostasis with age. Beyond ATP production, mitochondria orchestrate redox signaling, calcium handling, and apoptotic pathways, which are increasingly compromised in aged muscle due to chronic oxidative stress and defective quality control. High-resolution respirometry has revealed intrinsic, lifestyle-independent declines in mitochondrial respiratory capacity, while large-scale phenotyping and transcriptomic profiling have established robust associations between mitochondrial integrity, physical performance, and mobility. These findings have prompted a paradigm shift from static descriptions of mitochondrial decline toward dynamic analyses of mitochondrial signaling networks and stress adaptability. Several quality control mechanisms, including mitochondrial biogenesis, dynamics, mitophagy, and vesicle trafficking, emerge as critical regulators of myocyte integrity. Understanding how these systems deteriorate with age will be pivotal for developing therapeutic targets to preserve muscle function, mitigate sarcopenia, and extend health span.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"228 ","pages":"Article 112112"},"PeriodicalIF":5.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ABI3BP deficiency alleviates Ang II-induced VSMC senescence through the Nrf2 signalling pathway ABI3BP缺失通过NRF2信号通路缓解angii诱导的VSMC衰老

IF 5.1 3区医学

Mechanisms of Ageing and Development Pub Date : 2025-12-01 Epub Date: 2025-08-30 DOI: 10.1016/j.mad.2025.112104

Aiqiu Mao , Qiang Tu , Huaqiang Xie , Xiaoying Wang , Yuhan Liu , Yan Ding , Zheng Cao

{"title":"ABI3BP deficiency alleviates Ang II-induced VSMC senescence through the Nrf2 signalling pathway","authors":"Aiqiu Mao , Qiang Tu , Huaqiang Xie , Xiaoying Wang , Yuhan Liu , Yan Ding , Zheng Cao","doi":"10.1016/j.mad.2025.112104","DOIUrl":"10.1016/j.mad.2025.112104","url":null,"abstract":"<div><div>Vascular aging is a critical independent risk factor for cardiovascular disease (CVD), yet its precise molecular mechanisms remain poorly understood. In this study, we generated an ABI3BP knockout mouse to investigate the role of ABI3BP deficiency in angiotensin II (Ang II)-induced vascular aging. The results demonstrated that ABI3BP was highly expressed in AngII-induced senescent vascular smooth muscle cell (VSMC) and vascular tissues, with significantly increased expression also observed in the blood vessels of naturally aged mice. Downregulation of ABI3BP expression using siRNA significantly inhibited Ang II-induced senescence of VSMC. ABI3BP knockout ameliorated Ang II-induced vascular aging in mice, reduced the secretion of senescence-associated inflammatory factors IL-6 and TNF-α, alleviated senescence-induced accumulation of collagen in the vascular media and thickening of the vascular intima, and effectively suppressed Ang II-induced elevation of blood pressure. Further investigations revealed that these protective effects might be mediated through enhanced expression of Nrf2 and its downstream anti-aging factors. Silencing Nrf2 with siRNA attenuated the protective effects of ABI3BP downregulation on vascular aging. Overall, these findings demonstrate that ABI3BP downregulation inhibits VSMC senescence by enhancing the activity of the Nrf2-mediated antioxidant defense pathway, thereby attenuating the progression of vascular aging.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"228 ","pages":"Article 112104"},"PeriodicalIF":5.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Histone modifications: Key players in Alzheimer's disease 组蛋白修饰：阿尔茨海默病的关键因素

IF 5.1 3区医学

Mechanisms of Ageing and Development Pub Date : 2025-12-01 Epub Date: 2025-09-02 DOI: 10.1016/j.mad.2025.112102

Kun Li , Xiaolin Qiu , Qiqi Yang , Ziqiang Wang

引用次数: 0

Human astrocytes from healthy individuals and Alzheimer’s patients respond differently to Aβ1–42 oligomers, triggering distinct paths of reactivity and senescence 健康个体和阿尔茨海默病患者的人类星形胶质细胞对Aβ1-42寡聚物的反应不同，引发不同的反应性和衰老途径。

IF 5.1 3区医学

Mechanisms of Ageing and Development Pub Date : 2025-12-01 Epub Date: 2025-09-24 DOI: 10.1016/j.mad.2025.112116

Sara Ristori , Gianmarco Bertoni , Alessandra Bigi , Cristina Cecchi , Manuela Sollazzo , Luisa Iommarini , Daniela Monti , Elisa Bientinesi

{"title":"Human astrocytes from healthy individuals and Alzheimer’s patients respond differently to Aβ1–42 oligomers, triggering distinct paths of reactivity and senescence","authors":"Sara Ristori , Gianmarco Bertoni , Alessandra Bigi , Cristina Cecchi , Manuela Sollazzo , Luisa Iommarini , Daniela Monti , Elisa Bientinesi","doi":"10.1016/j.mad.2025.112116","DOIUrl":"10.1016/j.mad.2025.112116","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is a neurodegenerative disorder characterised by cognitive decline, amyloid-β (Aβ) plaques, and neurofibrillary tangles. Aβ<sub>1–42</sub> oligomers exert neurotoxic and pro-inflammatory effects. Astrocytes maintain brain homeostasis, and their dysfunction contributes to AD progression. This study investigates the impact of Aβ<sub>1–42</sub> oligomers on primary human astrocytes from healthy individuals and AD patients. Our findings show that astrocytes from both groups internalise Aβ<sub>1–42</sub> oligomers. In healthy astrocytes, internalisation enhances proteasome activity, whereas in AD astrocytes, it reduces it. Aβ<sub>1–42</sub> oligomers induce calcium dyshomeostasis and mitochondrial membrane potential alterations in both groups. Interestingly, oligomers induce apoptosis in a subset of healthy astrocytes, while surviving ones become reactive and hyperproliferative, releasing neuroinflammatory and neurotrophic molecules. Conversely, Aβ<sub>1–42</sub> drives AD astrocytes into senescence, characterised by increased β-galactosidase activity, p14<sup>ARF</sup> expression, senescence-associated secretory phenotype (SASP), and heterochromatin foci. Importantly, conditioned media from Aβ<sub>1–42</sub>-treated AD astrocytes, but not from healthy ones, cause death of differentiated SH-SY5Y neuron-like cells, suggesting that senescent astrocytes contribute to neurotoxicity. These findings reveal differential astrocytic responses to Aβ<sub>1–42</sub> oligomers, emphasising the importance of astrocyte senescence in AD pathogenesis. This research offers insight into cellular mechanisms underlying AD and may support the development of innovative therapeutic strategies for neurodegenerative diseases.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"228 ","pages":"Article 112116"},"PeriodicalIF":5.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145176423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IF 5.1 3区医学

Mechanisms of Ageing and Development Pub Date : 2025-12-01 Epub Date: 2025-11-19 DOI: 10.1016/j.mad.2025.112125

Di Hu, Wen Wen, Hui Li, Zuohui Zhang, Hong Lin, Jia Luo

{"title":"Age-related alterations in the expression of mesencephalic astrocyte-derived neurotrophic factor in the brain and their impact on neurobehavioral functions","authors":"Di Hu, Wen Wen, Hui Li, Zuohui Zhang, Hong Lin, Jia Luo","doi":"10.1016/j.mad.2025.112125","DOIUrl":"10.1016/j.mad.2025.112125","url":null,"abstract":"<div><div>Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a neurotrophic protein localized in the endoplasmic reticulum (ER) and pivotally involved in maintaining ER homeostasis. The ER is central to protein synthesis, folding, degradation and secretion (proteostasis), and experiences considerable stress in neurodegenerative diseases (NDDs), which activates the unfolded protein response (UPR). Aging, the primary risk factor for NDDS, is associated with impaired ER function. MANF is shown to be protective in various experimental models of NDDs. We hypothesized that the expression of MANF in the brain declines with age, which may increase the vulnerability to NDDs. We measured MANF levels in the brain and plasma of 1-, 4-, 11-, and 22-month-old male and female mice. A progressive decline of MANF levels was observed, with the lowest levels detected in 22 months. Reduced MANF expression was found in aged mice across several brain areas, including the cerebral cortex, olfactory bulb, thalamus, hypothalamus, hippocampus, and cerebellum. There was a sex difference in MANF levels in aged mice. Aging also altered the expression of UPR and MANF interacting proteins. Using cerebellar Purkinje cell (PC)-specific MANF deficient mice, we showed that MANF deficiency impaired motor coordination in female, but not male mice. MANF deficiency weakened spatial learning and memory in both male and female mice. Male MANF deficient mice displayed increased sociability, whereas female mice exhibit social withdrawal. Taken together, MANF expression in the brain declined with age and MANF deficiency impacted neurobehaviors in a sex-specific manner.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"228 ","pages":"Article 112125"},"PeriodicalIF":5.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145564292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An atlas of age- and sex-related volumetric alterations of grey matter in subcortical regions: The case of 46,111 UK Biobank participants 皮层下区域灰质年龄和性别相关体积变化图谱：46111名英国生物银行参与者的病例。

IF 5.1 3区医学

Mechanisms of Ageing and Development Pub Date : 2025-12-01 Epub Date: 2025-11-08 DOI: 10.1016/j.mad.2025.112123

Fatemeh Tabassi Mofrad, Chris Patrick Pflanz, John Gallacher

{"title":"An atlas of age- and sex-related volumetric alterations of grey matter in subcortical regions: The case of 46,111 UK Biobank participants","authors":"Fatemeh Tabassi Mofrad, Chris Patrick Pflanz, John Gallacher","doi":"10.1016/j.mad.2025.112123","DOIUrl":"10.1016/j.mad.2025.112123","url":null,"abstract":"<div><div>Ageing is commonly associated with neuroanatomical changes in brain structure, underscoring the importance of distinguishing normal age-related alterations from those linked to pathological neurodegeneration. Despite this critical need, a standardized benchmark for identifying brain volumetric signatures of ageing remains lacking, and the influence of biological sex on age-related changes in brain volume is not yet fully understood. To address the above-mentioned gaps, we employed T1-weighted MRI images of 46,111 cognitively healthy individuals aged 44–83 from the UK Biobank cohort, and generated comprehensive maps of all the linear and non-linear trajectories of alterations in the grey matter volumes (GMVs) of subcortical regions across males and females. According to our findings, Brainstem, bilateral Amygdala and Hippocampus are the most susceptible subcortical regions to age-related atrophy, with males being generally more prone to such alterations. However, ageing proves to have a dual function as we also observed age-related inflammation in GMVs of Pallidum and Caudate which accelerates during older age and remains consistent across males and females. Our findings guide regenerative strategies and therapeutic interventions by locating subcortical regions most vulnerable to age-related atrophy and inflammation and establish a benchmark for sex-specific typical patterns of subcortical grey matter alterations due to ageing.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"228 ","pages":"Article 112123"},"PeriodicalIF":5.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145489163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Diminished CEACAM1 level plays a critical role in age-related hepatic fibrosis CEACAM1水平降低在年龄相关性肝纤维化中起关键作用。

IF 5.1 3区医学

Mechanisms of Ageing and Development Pub Date : 2025-12-01 Epub Date: 2025-11-04 DOI: 10.1016/j.mad.2025.112122

Sobia Zaidi , Suman Asalla , Raziyeh Abdolahipour , Agnes O. Portuphy , Marziyeh S. Jahromi , Harrison T. Muturi , Getachew D. Belew , Ramiro Malgor , Sivarajan Kumarasamy , Sonia M. Najjar

{"title":"Diminished CEACAM1 level plays a critical role in age-related hepatic fibrosis","authors":"Sobia Zaidi , Suman Asalla , Raziyeh Abdolahipour , Agnes O. Portuphy , Marziyeh S. Jahromi , Harrison T. Muturi , Getachew D. Belew , Ramiro Malgor , Sivarajan Kumarasamy , Sonia M. Najjar","doi":"10.1016/j.mad.2025.112122","DOIUrl":"10.1016/j.mad.2025.112122","url":null,"abstract":"<div><h3>Background</h3><div>Hepatic fibrosis increases with aging, but its physiological progression and underlying mechanisms remain poorly defined. Given that CEACAM1 repression causes metabolic dysfunction and liver injury, the current studies investigated whether it mediates age-related hepatic fibrosis.</div></div><div><h3>Materials and methods</h3><div>The metabolic phenotype, histological, immunochemical and Western blot analyses were performed in male C57BL6/J wild-type and LCC1 mice with liver-specific CEACAM1 overexpression at 2–17 months of age.</div></div><div><h3>Results</h3><div>Progression of metabolic dysfunction during physiological aging began with increased lipolysis-derived fatty acids, followed by hepatic insulin resistance with compensatory increase in insulin secretion and a decline in hepatic insulin clearance mediated initially by compromised CEACAM1 phosphorylation and then expression. Resultant hyperinsulinemia drove hepatic steatosis, followed by Th1 inflammatory response and subsequently, hepatic fibrosis at 17 months of age. These histological abnormalities regressed in LCC1 mice with protected hepatic CEACAM1 levels. Accordingly, LCC1 mice exhibited survival advantage.</div></div><div><h3>Discussion</h3><div>This age-related mapping demonstrated that early metabolic alterations impaired insulin clearance with a progressive loss of CEACAM1. Resultant hyperinsulinemia drove hepatic steatosis followed by inflammation and ultimately, hepatic fibrosis in wild-type but not LCC1 mice. Together with survival benefit of LCC1, these observations propose that protecting hepatic CEACAM1 prevents age-related hepatic fibrosis and bestows longevity.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"228 ","pages":"Article 112122"},"PeriodicalIF":5.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145458845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The stress-responsive cytokine GDF-15 and sarcopenia: A systematic review and meta-analysis on aging muscle decline 应激反应细胞因子GDF-15和肌肉减少症：衰老肌肉衰退的系统回顾和荟萃分析。

IF 5.1 3区医学

Mechanisms of Ageing and Development Pub Date : 2025-12-01 Epub Date: 2025-09-26 DOI: 10.1016/j.mad.2025.112117

Mario Virgilio Papa , Chiara Ceolin , Francesco Boschele , Raffaele Pagliuca , Giuseppe Sergi , Marina De Rui

{"title":"The stress-responsive cytokine GDF-15 and sarcopenia: A systematic review and meta-analysis on aging muscle decline","authors":"Mario Virgilio Papa , Chiara Ceolin , Francesco Boschele , Raffaele Pagliuca , Giuseppe Sergi , Marina De Rui","doi":"10.1016/j.mad.2025.112117","DOIUrl":"10.1016/j.mad.2025.112117","url":null,"abstract":"<div><h3>Background</h3><div>Given the increasing interest for Growth Differentiation Factor-15 (GDF-15) in muscle decline, this study aims to evaluate the association between circulating levels of GDF-15 and muscle mass and sarcopenia through a systematic review and meta-analysis.</div></div><div><h3>Methods</h3><div>The research, in accordance with PRISMA and MOOSE guidelines, involved PubMed, Embase, and Cochrane Libraries. Two meta-analyses were performed: (1) comparison of GDF-15 levels in sarcopenic vs non-sarcopenic individuals; (2) correlation between GDF-15 and muscle mass.</div></div><div><h3>Results</h3><div>A total of 7 studies met the inclusion criteria (total n = 2344) enrolling both adults aged ≥ 60 years (6/7 studies) and a younger cohort (42 years [IQR 31.8–51]). The first meta-analysis, based on 4 studies (n = 1393), showed significantly higher levels of GDF-15 in sarcopenic individuals (r = 0.482). The second meta-analysis, involving 4 studies (n = 1400), found a significant inverse correlation between GDF-15 and muscle mass (r = -0.221).</div></div><div><h3>Conclusions</h3><div>Sarcopenic individuals had higher circulating GDF-15. Together with the inverse correlation between GDF-15 and muscle mass observed, these findings show a small-to-moderate association between elevated GDF-15 and sarcopenic phenotypes in older adults. However, the limited number of studies and high heterogeneity for the sarcopenia comparison warrant cautious interpretation and underscore the need for larger, longitudinal investigations.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"228 ","pages":"Article 112117"},"PeriodicalIF":5.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

DKK3, regulated by FOXF1-EZH2 axis, takes action on tubular epithelial cells senescence to trigger glomerular endothelial cells ferroptosis involving in renal fibrosis DKK3受FOXF1-EZH2轴调控，作用于小管上皮细胞衰老，触发肾小球内皮细胞铁上沉，参与肾纤维化。

IF 5.1 3区医学

Mechanisms of Ageing and Development Pub Date : 2025-12-01 Epub Date: 2025-08-28 DOI: 10.1016/j.mad.2025.112103

Huiling Cao , Yanxia Chen , Jinjing Huang, Weiping Tu, Ben Ke, Xiangdong Fang

{"title":"DKK3, regulated by FOXF1-EZH2 axis, takes action on tubular epithelial cells senescence to trigger glomerular endothelial cells ferroptosis involving in renal fibrosis","authors":"Huiling Cao , Yanxia Chen , Jinjing Huang, Weiping Tu, Ben Ke, Xiangdong Fang","doi":"10.1016/j.mad.2025.112103","DOIUrl":"10.1016/j.mad.2025.112103","url":null,"abstract":"<div><div>Chronic kidney disease (CKD) can be accelerated by renal fibrosis. Dickkopf-3 (DKK3) plays a role in regulating renal fibrosis, while tubular cell senescence contributes to fibrosis development. Here, the role and mechanism of DKK3 on senescence and renal fibrosis were evaluated. We demonstrated that in CKD patients and Unilateral Ureteral Obstruction (UUO) mice, downregulation of FOXF1 and upregulation of DDK3 was observed, of which expression patterns exhibited negative association. Reinforced FOXF1 protected against H<sub>2</sub>O<sub>2</sub>-triggered tubular cell damage, fibrosis, and senescence, which was reversed by DKK3 overexpression. In UUO mice, FOXF1 depletion worsened renal fibrosis and senescence. Mechanistically, FOXF1 was identified to be a transcriptional activator of EZH2 to mediated epigenetic silence of DKK3 via H3K27me3 levels. Moreover, exosomal DKK3 from tubular cells controlled Endothelial to Mesenchymal Transition, oxidative stress and ferroptosis in MRGECs. Overall, our data reveal that the FOXF1-EZH2-DKK3 axis controls tubular cell senescence. Exosome-borne DKK3 influences lipid peroxidation in glomerular endothelial cells, inducing ferroptosis and advancing renal fibrosis, which provides new therapeutic targets for CKD treatment.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"228 ","pages":"Article 112103"},"PeriodicalIF":5.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0