Mechanisms of Ageing and Development最新文献

Distinct Thermosensitive Activation of HSF1 and HSF2 in Immune Cells During Aging. 衰老过程中免疫细胞中HSF1和HSF2不同的热敏激活。

IF 6.5 3区医学

Mechanisms of Ageing and Development Pub Date : 2026-10-29 DOI: 10.1016/j.mad.2026.112268

Prachayaporn Prasertsuksri, Nathan A Velaris, Donald A Jurivich

{"title":"Distinct Thermosensitive Activation of HSF1 and HSF2 in Immune Cells During Aging.","authors":"Prachayaporn Prasertsuksri, Nathan A Velaris, Donald A Jurivich","doi":"10.1016/j.mad.2026.112268","DOIUrl":"https://doi.org/10.1016/j.mad.2026.112268","url":null,"abstract":"<p><p>Heat shock factors (HSF1 and HSF2) critically maintain proteostasis under stress, yet their activation across the continuum of rising temperatures is incompletely understood. Furthermore, how age impacts thermally driven rheostatic changes in stress responses is not fully elucidated. Here, we investigate how different temperature levels impact HSF1 and HSF2 in Jurkat T cells and splenocytes from young and aged mice. Using Western blotting, EMSA, RT-qPCR, immunofluorescence, and co-immunoprecipitation, we examined heat shock response changes across a range of thermal conditions. Unlike most cell types that require 42°C for HSF1 activation, Jurkat cells maximally responded at 41°C and splenocytes at 40°C. Optimal HSF1 activation coincided with maximal nuclear translocation, Ser326 phosphorylation, SIRT1 protein levels, and HSP RNA levels. By contrast, HSF2 nuclear translocation required a higher temperature (42°C) than HSF1. Age reduced HSF1 protein levels and nuclear translocation during thermal stress, while HSF2 protein levels were significantly elevated. These findings reveal distinct temperature-sensitive patterns of HSF1 and HSF2 activation of immunocytes during heat stress and identify age-associated alterations in this response.</p>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":" ","pages":"112268"},"PeriodicalIF":6.5,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149298730","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

Effects of the Pythagorean Self-Awareness Intervention on total oxidant status and telomere length in breast cancer survivors: A randomized controlled trial. 毕达哥拉斯自我意识干预对乳腺癌幸存者总氧化状态和端粒长度的影响：一项随机对照试验。

IF 6.5 3区医学

Mechanisms of Ageing and Development Pub Date : 2026-10-23 DOI: 10.1016/j.mad.2026.112263

Maria Charalampopoulou, George C Zografos, Dimitrios Tsakogiannis, Ioanna A Anastasiou, Garyfalia Bletsa, Dimitrios Tryfonopoulos, Panagiotis Daskalakis, George P Chrousos, Flora Bacopoulou, Flora Zagouri, Christina Darviri

{"title":"Effects of the Pythagorean Self-Awareness Intervention on total oxidant status and telomere length in breast cancer survivors: A randomized controlled trial.","authors":"Maria Charalampopoulou, George C Zografos, Dimitrios Tsakogiannis, Ioanna A Anastasiou, Garyfalia Bletsa, Dimitrios Tryfonopoulos, Panagiotis Daskalakis, George P Chrousos, Flora Bacopoulou, Flora Zagouri, Christina Darviri","doi":"10.1016/j.mad.2026.112263","DOIUrl":"https://doi.org/10.1016/j.mad.2026.112263","url":null,"abstract":"<p><strong>Background: </strong>Psychological stress and health behaviors are associated with oxidative status and telomere biology, but evidence from multidomain interventions in breast cancer survivors remains limited.</p><p><strong>Objective: </strong>To evaluate the effects of the Pythagorean Self-Awareness Intervention (PSAI) on biological, behavioral, and psychosocial outcomes following breast cancer treatment.</p><p><strong>Methods: </strong>In this randomized controlled trial, 120 women were randomized to an eight-week PSAI program or education-only control condition (n = 60 each); 118 were included in the modified intention-to-treat analysis. Primary biological outcomes were serum total oxidant status and PBMC relative telomere T/S ratio. Linear mixed-effects models estimated group × time effects, between-group differences in change, 95% confidence intervals (CIs), and Hedges' g.</p><p><strong>Results: </strong>Total oxidant status decreased more in the intervention group (difference in change, -3.83 μmol/L; 95% CI -7.03 to -0.63; p = 0.020; g = -0.13). Telomere-length change did not differ significantly between groups (-0.170log₂[T/S] units; 95% CI -0.554 to 0.214; p = 0.382; g = -0.23). PSAI also improved physical activity, body weight, sleep, perceived stress, anxiety, and depression.</p><p><strong>Conclusion: </strong>PSAI improved total oxidant status and several patient-relevant outcomes but did not significantly affect telomere-length change. Longer, adequately powered trials with repeated biomarker assessments are require.</p>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":" ","pages":"112263"},"PeriodicalIF":6.5,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149245266","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

Corrigendum to "SOX2 and NTF3 expression are associated with taste-bud alterations in aging klotho-deficient mice" [Mech. Ageing Develop. (2026) 112259]. “SOX2和NTF3的表达与衰老的klotho缺陷小鼠的味蕾改变有关”的勘误表。老龄化的发展。(2026) 112259)。

IF 6.5 3区医学

Mechanisms of Ageing and Development Pub Date : 2026-10-03 DOI: 10.1016/j.mad.2026.112262

Manh Dat Duong, Soo-A Kim, Sang-Gun Ahn

引用次数: 0

Expression of Concern to "Increased expression of heat shock proteins in rat brain during aging relationship with mitochondrial function and glutathione redox state" [Mech. Ageing Dev. 125(2004) 325-35]. 对“衰老过程中大鼠脑热休克蛋白表达增加与线粒体功能和谷胱甘肽氧化还原状态的关系”的关注表达[机制]。人口老龄化发展[j].社会科学进展，2004(1):325-35。

IF 6.5 3区医学

Mechanisms of Ageing and Development Pub Date : 2026-09-12 DOI: 10.1016/j.mad.2026.112256

V Calabrese, G Scapagnini, A Ravagna, C Colombrita, F Spadaro, D A Butterfield, A M Giuffrida Stella

引用次数: 0

Expression of Concern to "CHIP E3 ligase regulates mammalian senescence by modulating the levels of oxidized proteins" [Mech. Ageing Dev. 132 (2011) 269-272]. 对“CHIP E3连接酶通过调节氧化蛋白水平调节哺乳动物衰老”的关注表达[Mech。老龄化发展[j].社会科学进展，2011(4):669 - 672。

IF 5.1 3区医学

Mechanisms of Ageing and Development Pub Date : 2026-06-01 Epub Date: 2026-04-11 DOI: 10.1016/j.mad.2026.112182

Christina Sisoula, Efstathios S Gonos

引用次数: 0

SRC suppression attenuates vascular aging by activating FUNDC1-dependent mitophagy SRC抑制通过激活fundc1依赖的线粒体自噬来减缓血管老化。

IF 5.1 3区医学

Mechanisms of Ageing and Development Pub Date : 2026-04-01 Epub Date: 2026-01-15 DOI: 10.1016/j.mad.2026.112156

Linghuan Wang , Yan Ma , Tianhu Wang , Weiwei Zhang , Zhiyi Fang , Tingting Lu , Yingjie Zhang , Yan Fang , Ting Sun , Dong Han , Feng Cao

{"title":"SRC suppression attenuates vascular aging by activating FUNDC1-dependent mitophagy","authors":"Linghuan Wang , Yan Ma , Tianhu Wang , Weiwei Zhang , Zhiyi Fang , Tingting Lu , Yingjie Zhang , Yan Fang , Ting Sun , Dong Han , Feng Cao","doi":"10.1016/j.mad.2026.112156","DOIUrl":"10.1016/j.mad.2026.112156","url":null,"abstract":"<div><div>Vascular smooth muscle cell senescence contributes critically to vascular remodeling and atherosclerosis, with mitochondrial dysfunction and impaired mitophagy recognized as major contributors. SRC, a stress-responsive tyrosine kinase, has been linked to aging, yet its role in vascular aging remains unclear. Here, we examined the role of SRC in regulating autophagy/mitophagy using <em>in vitro</em> and <em>in vivo</em> models. An accelerated vascular aging model was established using a high-fat diet and streptozotocin injection in ApoE<sup>-/-</sup> mice, while senescence in mouse aortic vascular smooth muscle cells (MOVASs) was induced by doxorubicin. Elevated expression of SRC and phosphorylated SRC (Tyr418) was confirmed in both models. Pharmacological inhibition of SRC with KX2–391 partially mitigated features of vascular aging, improved mitochondrial morphology, reduced plaque burden, and enhanced fibrous cap stability. In senescent MOVASs, SRC knockdown decreased FUNDC1 Tyr18 phosphorylation, enhanced mitophagic flux, and reduced senescence, whereas SRC overexpression produced opposite effects and impaired KX2–391–mediated protection. Moreover, FUNDC1 knockdown abolished the anti-senescence effects of KX2–391, confirming that FUNDC1 is essential for SRC-mediated regulation. Together, these findings establish the SRC–FUNDC1 axis as an important regulator of mitophagy and vascular aging, suggesting that SRC inhibition may offer therapeutic benefit against vascular senescence and atherosclerosis.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"230 ","pages":"Article 112156"},"PeriodicalIF":5.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994313","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

Inflammatory and genetic mechanisms mediate the association between frailty and incident atopic dermatitis in middle-aged and elderly adults 炎症和遗传机制介导虚弱和中老年人特应性皮炎之间的关联

IF 5.1 3区医学

Mechanisms of Ageing and Development Pub Date : 2026-04-01 Epub Date: 2026-01-05 DOI: 10.1016/j.mad.2025.112148

Peizhi Deng , Siyu Tang , Jinron Zeng , Jianyun Lu

{"title":"Inflammatory and genetic mechanisms mediate the association between frailty and incident atopic dermatitis in middle-aged and elderly adults","authors":"Peizhi Deng , Siyu Tang , Jinron Zeng , Jianyun Lu","doi":"10.1016/j.mad.2025.112148","DOIUrl":"10.1016/j.mad.2025.112148","url":null,"abstract":"<div><div>Frailty is linked to many chronic conditions, but its relationship with atopic dermatitis (AD) remains insufficiently defined. We assessed whether frailty predisposes to incident AD and explored inflammatory and genetic mechanisms. Baseline frailty was ascertained using both the physical frailty phenotype and a multidimensional frailty index, classifying participants as non-frail, pre-frail, or frail. Cox proportional hazards models with stratified analyses quantified associations with AD onset. To probe causality, we performed two-sample Mendelian randomization (TSMR) and generalized summary-data-based MR (GSMR). We further integrated circulating inflammatory markers and plasma proteomic data to illuminate biological pathways. Compared with non-frail participants, pre-frail and frail individuals had higher risks of incident AD after adjustment for established confounders; associations were stronger in adults < 65 years. TSMR and GSMR supported a potential causal effect of frailty on AD. Neutrophil count, eosinophil count, and C-reactive protein partially mediated the frailty-AD relationship. Proteomic analyses highlighted MMP12 as a promising AD-specific biomarker in frail individuals. Overall, frailty confers an elevated long-term risk of AD, with middle-aged adults displaying the greatest vulnerability. Several inflammatory cell measures and circulating proteins-including MMP12-may serve as early indicators of AD risk, informing earlier diagnosis and targeted monitoring in pre-frail and frail populations.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"230 ","pages":"Article 112148"},"PeriodicalIF":5.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145915215","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

Senescent cancer-associated fibroblasts in cancer progression: From formation to therapeutic opportunities 癌症进展中的衰老癌症相关成纤维细胞：从形成到治疗机会

IF 5.1 3区医学

Mechanisms of Ageing and Development Pub Date : 2026-04-01 Epub Date: 2026-01-21 DOI: 10.1016/j.mad.2026.112158

Yingying Feng, Xiaochen Zhi, Ting Xiao, Lin Feng

{"title":"Senescent cancer-associated fibroblasts in cancer progression: From formation to therapeutic opportunities","authors":"Yingying Feng, Xiaochen Zhi, Ting Xiao, Lin Feng","doi":"10.1016/j.mad.2026.112158","DOIUrl":"10.1016/j.mad.2026.112158","url":null,"abstract":"<div><div>Cancer-associated fibroblasts (CAFs) are a key cellular component of the tumor microenvironment (TME), which comprises distinct subtypes, each exhibiting unique and significant roles in cancer development. Senescent cancer-associated fibroblasts (senCAFs) are a newly identified subset of CAFs characterized by high expression of senescence-associated markers. Notably, senCAFs significantly promote tumor malignancy through the secretion of diverse senescence-associated secretory phenotype (SASP) factors, such as interleukin-6 (IL-6), interleukin-8 (IL-8), matrix metalloproteinases (MMPs), and transforming growth factor-β (TGF-β), thereby facilitating tumor cell proliferation, invasion, angiogenesis, immunosuppression, and resistance to cancer therapy. Consequently, targeting senCAFs—either through selective clearance of this cell subset or suppression of their SASP—represents a promising approach for cancer treatment. Emerging therapies include pharmacological inhibition of key SASP regulatory pathways (e.g., JAK/STAT3 and NF-κB) and antagonists targeting individual SASP components. Additionally, senolytic agents and therapies targeting senCAF-specific markers (e.g., TSPAN8) are being actively explored. Furthermore, immunotherapies, including CAR-T cells targeting senescence-associated surface proteins, provide intriguing avenues. These advances highlight senCAFs as attractive therapeutic targets and underscore the potential for integrating SASP inhibitors and senolytic agents into precision oncology paradigms.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"230 ","pages":"Article 112158"},"PeriodicalIF":5.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035545","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

Vitisin B rejuvenates senescence via WBP2NL regulation 维生素B通过调控WBP2NL使衰老恢复活力

IF 5.1 3区医学

Mechanisms of Ageing and Development Pub Date : 2026-04-01 Epub Date: 2026-01-21 DOI: 10.1016/j.mad.2026.112159

Jee Hee Yoon , Yun Haeng Lee , Sekyung Oh , Kyeong Seon Lee , Ji Ho Park , Yoo Jin Lee , Byeonghyeon So , Duyeol Kim , Minseon Kim , Hyung Wook Kwon , Youngjoo Byun , Ki Yong Lee , Joon Tae Park

{"title":"Vitisin B rejuvenates senescence via WBP2NL regulation","authors":"Jee Hee Yoon , Yun Haeng Lee , Sekyung Oh , Kyeong Seon Lee , Ji Ho Park , Yoo Jin Lee , Byeonghyeon So , Duyeol Kim , Minseon Kim , Hyung Wook Kwon , Youngjoo Byun , Ki Yong Lee , Joon Tae Park","doi":"10.1016/j.mad.2026.112159","DOIUrl":"10.1016/j.mad.2026.112159","url":null,"abstract":"<div><div>One of the main factors contributing to aging is reactive oxygen species (ROS), which are produced by dysfunctional mitochondria. Reducing ROS generation is considered an essential treatment for senescence, but no effective treatment has been developed yet. In this study, vitisin B, a tetramer of resveratrol, was found to be an efficient reagent that reduces mitochondrial ROS generation after screening phenylpropanoids (PPs), metabolites produced to overcome ROS-mediated stress in plants. Vitisin B induced mitochondrial functional recovery by activating mitophagy and removing dysfunctional mitochondria. Mitochondrial functional recovery by vitisin B decreased mitochondrial ROS, a by-product generated from dysfunctional mitochondria. In addition, ROS reduction by vitisin B restored senescence-associated phenotypes. RNA sequencing identified <em>WBP2 N-Terminal Like</em> (<em>WBP2NL</em>) as a gene essential for vitisin B-mediated senescence rejuvenation. Knockdown of <em>WBP2NL</em> exhibited effects similar to those of vitisin B, reducing mitochondrial ROS generation and consequently reversing senescence-associated phenotypes. This study elucidates a novel mechanism by which vitisin B reverses senescence by lowering mitochondrial ROS generation. This discovery opens the way to new therapeutic options to control aging by modulating mitochondrial ROS production.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"230 ","pages":"Article 112159"},"PeriodicalIF":5.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035490","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

Dietary restriction mitigates cognitive impairments in a mouse model of SCA19/22 饮食限制减轻sc19 /22小鼠模型的认知障碍。

IF 5.1 3区医学

Mechanisms of Ageing and Development Pub Date : 2026-04-01 Epub Date: 2026-01-17 DOI: 10.1016/j.mad.2026.112157

Cheng-Yun Ma , Sheng-Rong Yeh , Yi-Hsuan Huang , Wei-Sheng Lin , Yi-Chung Lee , Ting-Fen Tsai , Shou-Zen Fan , Pei-Yu Wang

{"title":"Dietary restriction mitigates cognitive impairments in a mouse model of SCA19/22","authors":"Cheng-Yun Ma , Sheng-Rong Yeh , Yi-Hsuan Huang , Wei-Sheng Lin , Yi-Chung Lee , Ting-Fen Tsai , Shou-Zen Fan , Pei-Yu Wang","doi":"10.1016/j.mad.2026.112157","DOIUrl":"10.1016/j.mad.2026.112157","url":null,"abstract":"<div><div>Spinocerebellar ataxia types 19 and 22 (SCA19/22) are neurodegenerative disorders caused by mutations in <em>KCND3</em> (potassium voltage-gated channel subfamily D member 3). Previous studies have developed <em>Kcnd3</em> F227del knock-in (KI) mice that successfully recapitulate the motor deficits and molecular pathogenesis observed in patients. However, the broader neurobehavioral consequences of the humanized <em>Kcnd3</em> F227del mutation, and whether these phenotypes depend on functional <em>Kcnd3</em>, remain unclear. In this study, we employed a battery of behavioral assessments and found that the <em>Kcnd3</em> F227del mutation may not only result in a loss of function but also act as a dominant, toxic gain-of-function variant associated with both ataxia and memory impairments. In contrast, <em>Kcnd3</em> null mice exhibited primarily hyperactivity without major cognitive deficits. Furthermore, we demonstrated that dietary restriction (DR) effectively attenuates memory deficits but does not improve locomotor impairments in <em>Kcnd3</em> F227del KI mice at behavioral, cellular, and neurostructural levels. Specifically, DR preserved neuronal survival, maintained dendritic architecture and spine density, and reduced neuroinflammation in the hippocampus. These findings offer new insights into the etiology of SCA19/22-related symptoms and suggest that DR may serve as a potential therapeutic strategy targeting cognitive deficits in patients carrying the <em>KCND3</em> F227del mutation.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"230 ","pages":"Article 112157"},"PeriodicalIF":5.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003649","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