首页 > 最新文献

GeroScience最新文献

英文 中文
Hierarchical disruption of lateral prefrontal cortex gradients in cognitive aging. 认知老化中外侧前额叶皮层梯度的分层破坏。
IF 5.6 2区 医学 Q1 GERIATRICS & GERONTOLOGY Pub Date : 2026-01-23 DOI: 10.1007/s11357-025-02094-7
Hai-Yan Hou,Ping Wang,Sheng-Ju Guo,Hui-Jie Li
The lateral prefrontal cortex (LPFC) plays a pivotal role in executive functions and exhibits a hierarchical rostro-caudal organization critical for higher-order cognition. Using connectome gradient mapping of resting-state fMRI data across young, middle-aged, and older adults (N = 478), we found preserved global gradient structure but significant compression of the principal gradient in older adults relative to middle-aged adults, particularly in dorsolateral (DLPFC) and frontopolar (FPC) regions. This reduced functional differentiation corresponded to lower spatial separation between LPFC subdivisions. Meta-analytic decoding linked these changes to attenuated engagement of executive functions. Crucially, in an independent cohort of older adults (N = 99), individuals with better executive function exhibited greater gradient range and variation at the global level, along with higher gradient values in the DLPFC and ventrolateral prefrontal cortex (VLPFC) and lower values in the premotor cortex at the regional level. These findings suggest that age-related disruption of LPFC gradient organization may reflect neural dedifferentiation and is closely related to executive decline. Gradient compression in the LPFC may serve as a novel biomarker of cognitive aging, offering insights into the hierarchical reorganization of brain networks in late life.
侧前额叶皮层(LPFC)在执行功能中起着关键作用,并表现出对高阶认知至关重要的纵向-尾部分层组织。利用青年人、中年人和老年人静息状态fMRI数据的连接组梯度映射(N = 478),我们发现与中年人相比,老年人的整体梯度结构得到了保留,但主梯度明显压缩,特别是在背外侧(DLPFC)和额极(FPC)区域。这种减少的功能分化对应于LPFC细分之间较低的空间分离。元分析解码将这些变化与执行功能的减弱联系起来。重要的是,在一个独立的老年人队列(N = 99)中,执行功能较好的个体在整体水平上表现出更大的梯度范围和变化,同时DLPFC和腹外侧前额叶皮层(VLPFC)的梯度值较高,而运动前皮层在区域水平上的梯度值较低。这些发现表明,年龄相关的LPFC梯度组织破坏可能反映了神经去分化,并与执行能力下降密切相关。LPFC的梯度压缩可能作为认知衰老的一种新的生物标志物,为研究晚年大脑网络的分层重组提供了新的见解。
{"title":"Hierarchical disruption of lateral prefrontal cortex gradients in cognitive aging.","authors":"Hai-Yan Hou,Ping Wang,Sheng-Ju Guo,Hui-Jie Li","doi":"10.1007/s11357-025-02094-7","DOIUrl":"https://doi.org/10.1007/s11357-025-02094-7","url":null,"abstract":"The lateral prefrontal cortex (LPFC) plays a pivotal role in executive functions and exhibits a hierarchical rostro-caudal organization critical for higher-order cognition. Using connectome gradient mapping of resting-state fMRI data across young, middle-aged, and older adults (N = 478), we found preserved global gradient structure but significant compression of the principal gradient in older adults relative to middle-aged adults, particularly in dorsolateral (DLPFC) and frontopolar (FPC) regions. This reduced functional differentiation corresponded to lower spatial separation between LPFC subdivisions. Meta-analytic decoding linked these changes to attenuated engagement of executive functions. Crucially, in an independent cohort of older adults (N = 99), individuals with better executive function exhibited greater gradient range and variation at the global level, along with higher gradient values in the DLPFC and ventrolateral prefrontal cortex (VLPFC) and lower values in the premotor cortex at the regional level. These findings suggest that age-related disruption of LPFC gradient organization may reflect neural dedifferentiation and is closely related to executive decline. Gradient compression in the LPFC may serve as a novel biomarker of cognitive aging, offering insights into the hierarchical reorganization of brain networks in late life.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"275 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
DNA methylation-based surrogate markers of C-reactive protein and their associations with health-related traits. 基于DNA甲基化的c反应蛋白替代标记及其与健康相关特征的关联
IF 5.6 2区 医学 Q1 GERIATRICS & GERONTOLOGY Pub Date : 2026-01-22 DOI: 10.1007/s11357-025-02085-8
Danmeng Lily Li,Allison M Hodge,Joanne Ryan,Melissa C Southey,Graham G Giles,Roger L Milne,Pierre-Antoine Dugué
Several methylation-based surrogate markers of C-reactive protein (mCRP) have been proposed and used to assess the risk of age-related phenotypes and construct novel ageing markers. We aimed to (i) assess the variance in plasma CRP explained by several mCRP markers; (ii) compare their associations with three health-related traits: mortality, body mass index (BMI), and PCGrimAge; and (iii) assess the stability of CRP and mCRP over a decade. Blood samples were collected from 947 participants in the Melbourne Collaborative Cohort Study at baseline (1990-1994) and wave 2 (2003-2007). High-sensitivity CRP was measured in plasma samples. Five mCRP markers were calculated: mCRP-Ligthart, mCRP-Wielscher, mCRP-EpiScore, mCRP-GrimAge2, and mCRP-Hillary. Intraclass correlation coefficients (ICCs) were calculated to assess the stability of CRP/mCRP between baseline and wave 2. Associations of wave 2 CRP/mCRP with mortality (Ndeaths = 319) were assessed using Cox models and linear regression for BMI and age-adjusted PCGrimAge. mCRP explained 6.0% (mCRP-Wielscher) to 16.8% (mCRP-GrimAge2) of the variance in plasma CRP. The ICCs for CRP and mCRP markers were similar, ranging from 0.44 (mCRP-GrimAge2) to 0.63 (mCRP-Wielscher). Compared with CRP, mCRP had stronger associations with PCGrimAge, whereas for mortality and BMI, the associations were similar or weaker for mCRP. Associations between mCRP and mortality were greatly attenuated after adjusting for PCGrimAge but less so after adjusting for CRP. The association of CRP with mortality remained strong after adjusting for mCRP. Our study validated mCRP markers and clarified the role of CRP and mCRP in ageing, which may inform the use and development of ageing biomarkers.
已经提出了几种基于甲基化的c反应蛋白(mCRP)替代标记物,并用于评估年龄相关表型的风险和构建新的衰老标记物。我们的目的是(i)评估由几种mCRP标志物解释的血浆CRP的差异;(ii)比较它们与三个健康相关特征的关联:死亡率、体重指数(BMI)和PCGrimAge;(iii)评估CRP和mCRP在十年内的稳定性。在墨尔本合作队列研究的基线(1990-1994)和第二阶段(2003-2007)收集了947名参与者的血液样本。在血浆样品中检测高敏CRP。计算五种mCRP标记物:mCRP- lighthart、mCRP- wielscher、mCRP- episcore、mCRP- grimage2和mCRP- hillary。计算类内相关系数(ICCs)以评估CRP/mCRP在基线和第2波之间的稳定性。使用Cox模型和BMI及年龄调整后的PCGrimAge线性回归评估wave 2 CRP/mCRP与死亡率(Ndeaths = 319)的关系。mCRP解释了6.0% (mCRP- wielscher)至16.8% (mCRP- grimage2)的血浆CRP差异。CRP和mCRP标志物的ICCs相似,范围从0.44 (mCRP- grimage2)到0.63 (mCRP- wielscher)。与CRP相比,mCRP与pcgrmage有较强的相关性,而对于死亡率和BMI, mCRP的相关性相似或较弱。调整PCGrimAge后,mCRP与死亡率之间的相关性大大减弱,但调整CRP后相关性减弱。在调整mCRP后,CRP与死亡率的相关性仍然很强。我们的研究验证了mCRP标志物的有效性,并阐明了CRP和mCRP在衰老中的作用,这可能为衰老生物标志物的使用和开发提供信息。
{"title":"DNA methylation-based surrogate markers of C-reactive protein and their associations with health-related traits.","authors":"Danmeng Lily Li,Allison M Hodge,Joanne Ryan,Melissa C Southey,Graham G Giles,Roger L Milne,Pierre-Antoine Dugué","doi":"10.1007/s11357-025-02085-8","DOIUrl":"https://doi.org/10.1007/s11357-025-02085-8","url":null,"abstract":"Several methylation-based surrogate markers of C-reactive protein (mCRP) have been proposed and used to assess the risk of age-related phenotypes and construct novel ageing markers. We aimed to (i) assess the variance in plasma CRP explained by several mCRP markers; (ii) compare their associations with three health-related traits: mortality, body mass index (BMI), and PCGrimAge; and (iii) assess the stability of CRP and mCRP over a decade. Blood samples were collected from 947 participants in the Melbourne Collaborative Cohort Study at baseline (1990-1994) and wave 2 (2003-2007). High-sensitivity CRP was measured in plasma samples. Five mCRP markers were calculated: mCRP-Ligthart, mCRP-Wielscher, mCRP-EpiScore, mCRP-GrimAge2, and mCRP-Hillary. Intraclass correlation coefficients (ICCs) were calculated to assess the stability of CRP/mCRP between baseline and wave 2. Associations of wave 2 CRP/mCRP with mortality (Ndeaths = 319) were assessed using Cox models and linear regression for BMI and age-adjusted PCGrimAge. mCRP explained 6.0% (mCRP-Wielscher) to 16.8% (mCRP-GrimAge2) of the variance in plasma CRP. The ICCs for CRP and mCRP markers were similar, ranging from 0.44 (mCRP-GrimAge2) to 0.63 (mCRP-Wielscher). Compared with CRP, mCRP had stronger associations with PCGrimAge, whereas for mortality and BMI, the associations were similar or weaker for mCRP. Associations between mCRP and mortality were greatly attenuated after adjusting for PCGrimAge but less so after adjusting for CRP. The association of CRP with mortality remained strong after adjusting for mCRP. Our study validated mCRP markers and clarified the role of CRP and mCRP in ageing, which may inform the use and development of ageing biomarkers.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"30 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Is the emerging influenza A(H3N2) K subclade a specific threat for older adults? 新出现的甲型流感(H3N2) K亚支是否对老年人构成特定威胁?
IF 5.6 2区 医学 Q1 GERIATRICS & GERONTOLOGY Pub Date : 2026-01-21 DOI: 10.1007/s11357-026-02108-y
Jorge Quarleri,M Victoria Delpino
{"title":"Is the emerging influenza A(H3N2) K subclade a specific threat for older adults?","authors":"Jorge Quarleri,M Victoria Delpino","doi":"10.1007/s11357-026-02108-y","DOIUrl":"https://doi.org/10.1007/s11357-026-02108-y","url":null,"abstract":"","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"49 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Tai Chi modulating multimodal connectivity patterns and cognitive function in cerebral small vessel disease. 太极对脑血管疾病多模态连接模式和认知功能的调节。
IF 5.6 2区 医学 Q1 GERIATRICS & GERONTOLOGY Pub Date : 2026-01-21 DOI: 10.1007/s11357-026-02106-0
Xiaoyong Zhong,Zhongpeng Dai,Liuxi Chu,Hongliang Zhou,Wanqing Lin,Bin Chen
Cerebral small vessel disease (CSVD) significantly contributes to cognitive decline and poses potential risk factors for both dementia and acute cerebrovascular events. Tai Chi has been recognized as an effective mind-body intervention for enhancing cognitive function and promoting neural plasticity. However, the neurobiological mechanisms that underlie how Tai Chi exercises affect cognitive improvement in patients with CSVD remain unclear. We recruited 51 patients with CSVD, randomly assigning them to either a 24-week Tai Chi exercise group (n = 26) or a health education control group (n = 25). We collected and analyzed data on neuropsychological assessments, plasma homocysteine levels, and brain structural and functional connectivity (SC and FC). Additionally, we employed network-based statistics along with correlational and mediation effect analyses to analyze the intervention process. Patients in the intervention group demonstrated a significant improvement in cognitive function. Furthermore, they demonstrated an increased FC pattern in the frontal-parietal-occipital regions, along with a significant rise of structural-functional coupling within the frontal network and a reduction in the occipital network. The enhanced structural-functional coupling in the frontal network partially mediated the reduction in homocysteine levels and the improvement in cognitive function.
脑血管病(CSVD)显著导致认知能力下降,并构成痴呆和急性脑血管事件的潜在危险因素。太极拳被认为是一种有效的身心干预,可以增强认知功能,促进神经可塑性。然而,太极拳运动如何影响心血管疾病患者认知改善的神经生物学机制尚不清楚。我们招募了51例CSVD患者,将他们随机分配到24周的太极运动组(n = 26)和健康教育对照组(n = 25)。我们收集并分析了神经心理学评估、血浆同型半胱氨酸水平以及大脑结构和功能连通性(SC和FC)的数据。此外,我们采用基于网络的统计,结合相关效应和中介效应分析来分析干预过程。干预组患者的认知功能有显著改善。此外,他们还发现前额-顶叶-枕叶区域的FC模式增加,同时额叶网络内结构-功能耦合显著增加,枕叶网络减少。额叶网络结构-功能耦合的增强部分介导了同型半胱氨酸水平的降低和认知功能的改善。
{"title":"Tai Chi modulating multimodal connectivity patterns and cognitive function in cerebral small vessel disease.","authors":"Xiaoyong Zhong,Zhongpeng Dai,Liuxi Chu,Hongliang Zhou,Wanqing Lin,Bin Chen","doi":"10.1007/s11357-026-02106-0","DOIUrl":"https://doi.org/10.1007/s11357-026-02106-0","url":null,"abstract":"Cerebral small vessel disease (CSVD) significantly contributes to cognitive decline and poses potential risk factors for both dementia and acute cerebrovascular events. Tai Chi has been recognized as an effective mind-body intervention for enhancing cognitive function and promoting neural plasticity. However, the neurobiological mechanisms that underlie how Tai Chi exercises affect cognitive improvement in patients with CSVD remain unclear. We recruited 51 patients with CSVD, randomly assigning them to either a 24-week Tai Chi exercise group (n = 26) or a health education control group (n = 25). We collected and analyzed data on neuropsychological assessments, plasma homocysteine levels, and brain structural and functional connectivity (SC and FC). Additionally, we employed network-based statistics along with correlational and mediation effect analyses to analyze the intervention process. Patients in the intervention group demonstrated a significant improvement in cognitive function. Furthermore, they demonstrated an increased FC pattern in the frontal-parietal-occipital regions, along with a significant rise of structural-functional coupling within the frontal network and a reduction in the occipital network. The enhanced structural-functional coupling in the frontal network partially mediated the reduction in homocysteine levels and the improvement in cognitive function.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"35 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Age and sex shape plasma lipid associations to skeletal muscle mitochondrial respiration and H2O2 emission. 年龄和性别影响血浆脂质与骨骼肌线粒体呼吸和H2O2排放的关系。
IF 5.6 2区 医学 Q1 GERIATRICS & GERONTOLOGY Pub Date : 2026-01-19 DOI: 10.1007/s11357-025-02047-0
Nicholas A Carlini,Bradley A Ruple,Helya Rostamkhani,Huihui Shi,J Alan Maschek,Brady E Hanson,Namakkal Soorappan Rajasekaran,Russell S Richardson,Micah J Drummond,Ryan M Broxterman,Joel D Trinity
Aging changes the lipidome and mitochondrial function in a sex-dependent manner, yet their associations remain poorly understood. Twenty-four younger (7M/17F) and forty-three older (21M/22F) adults underwent blood draws and skeletal muscle biopsies for this cross-sectional investigation. Plasma lipidomic profiling was performed via liquid chromatography-tandem mass spectrometry, while peak mitochondrial O2 utilization (OXPHOS) and hydrogen peroxide (H2O2) emission were assessed using high-resolution respirometry. Plasma lipidomic analysis annotated 535 lipid species across 28 different lipid classes. Lipid-age associations were identified in four lipid classes for both sexes with twelve lipid classes demonstrating sex-specific associations, including triglycerides (TG), carnitines (CAR), and fatty acids (FA). For lipid-OXPHOS interactions, the primary lipid class and species associated with higher OXPHOS exclusively in males were ceramides (CER) and dimethyl cholesterol esters (dimethyl-CE), while TG were the primary lipid species associated with impaired OXPHOS in females. For lipid-H2O2 interactions, the primary lipid class and species associated with higher H2O2 were methyl desmosteryl esters (methyl-DE), methyl cholesterol esters (methyl-CE), FA and TG in males whereas females exhibited 10 (CE, SM, LPC, dihexosylceramides (Hex2Cer), LPE, PI, HexCer, LPI, CAR, and hexosyl-N-acetylneuraminyl-ceramides (Hex2NeuAcCer)) lipid classes associated exclusively with H2O2 emission. These findings establish novel age- and sex-specific relationships between age-related changes in plasma lipids and skeletal muscle mitochondrial function, revealing distinct lipid signatures for respiration and H2O2 emission in males and females.
衰老以性别依赖的方式改变脂质组和线粒体功能,但它们之间的关联仍然知之甚少。24名年轻人(7米/17层)和43名老年人(21米/22层)接受了抽血和骨骼肌活检。通过液相色谱-串联质谱法进行血浆脂质组学分析,同时使用高分辨率呼吸仪评估线粒体O2利用率(OXPHOS)和过氧化氢(H2O2)排放峰值。血浆脂质组学分析注释了28个不同脂类的535种脂质。在两性的四类脂质中发现了脂质年龄相关性,其中有十二类脂质显示出性别特异性相关性,包括甘油三酯(TG)、肉碱(CAR)和脂肪酸(FA)。在脂质-OXPHOS相互作用中,仅在男性中与较高OXPHOS相关的主要脂类和种类是神经酰胺(CER)和二甲基胆固醇酯(dimethyl- ce),而在女性中与OXPHOS受损相关的主要脂类是TG。对于脂质-H2O2相互作用,与较高H2O2相关的主要脂类和种类是雄性的甲基去氨酯(甲基- de)、甲基胆固醇酯(甲基-CE)、FA和TG,而雌性则表现出10种(CE、SM、LPC、二己基神经酰胺(Hex2Cer)、LPE、PI、HexCer、LPI、CAR和己基- n -乙酰神经酰胺(Hex2NeuAcCer))脂类,它们只与H2O2排放相关。这些发现在年龄相关的血浆脂质变化和骨骼肌线粒体功能之间建立了新的年龄和性别特异性关系,揭示了男性和女性呼吸和H2O2排放的不同脂质特征。
{"title":"Age and sex shape plasma lipid associations to skeletal muscle mitochondrial respiration and H2O2 emission.","authors":"Nicholas A Carlini,Bradley A Ruple,Helya Rostamkhani,Huihui Shi,J Alan Maschek,Brady E Hanson,Namakkal Soorappan Rajasekaran,Russell S Richardson,Micah J Drummond,Ryan M Broxterman,Joel D Trinity","doi":"10.1007/s11357-025-02047-0","DOIUrl":"https://doi.org/10.1007/s11357-025-02047-0","url":null,"abstract":"Aging changes the lipidome and mitochondrial function in a sex-dependent manner, yet their associations remain poorly understood. Twenty-four younger (7M/17F) and forty-three older (21M/22F) adults underwent blood draws and skeletal muscle biopsies for this cross-sectional investigation. Plasma lipidomic profiling was performed via liquid chromatography-tandem mass spectrometry, while peak mitochondrial O2 utilization (OXPHOS) and hydrogen peroxide (H2O2) emission were assessed using high-resolution respirometry. Plasma lipidomic analysis annotated 535 lipid species across 28 different lipid classes. Lipid-age associations were identified in four lipid classes for both sexes with twelve lipid classes demonstrating sex-specific associations, including triglycerides (TG), carnitines (CAR), and fatty acids (FA). For lipid-OXPHOS interactions, the primary lipid class and species associated with higher OXPHOS exclusively in males were ceramides (CER) and dimethyl cholesterol esters (dimethyl-CE), while TG were the primary lipid species associated with impaired OXPHOS in females. For lipid-H2O2 interactions, the primary lipid class and species associated with higher H2O2 were methyl desmosteryl esters (methyl-DE), methyl cholesterol esters (methyl-CE), FA and TG in males whereas females exhibited 10 (CE, SM, LPC, dihexosylceramides (Hex2Cer), LPE, PI, HexCer, LPI, CAR, and hexosyl-N-acetylneuraminyl-ceramides (Hex2NeuAcCer)) lipid classes associated exclusively with H2O2 emission. These findings establish novel age- and sex-specific relationships between age-related changes in plasma lipids and skeletal muscle mitochondrial function, revealing distinct lipid signatures for respiration and H2O2 emission in males and females.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"22 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Epigenetic insights of Olympic champions: nuclear and mitochondrial DNA methylation and regulators of aging. 奥运冠军的表观遗传学见解:核和线粒体DNA甲基化和衰老调节因子。
IF 5.6 2区 医学 Q1 GERIATRICS & GERONTOLOGY Pub Date : 2026-01-17 DOI: 10.1007/s11357-025-02092-9
Timea Teglas,Ferenc Torma,Zoltan Bori,Dora Aczel,Gergely Babszky,Takuji Kawamura,Mitsuru Higuchi,Gu Yaodong,Muhammad Lee,Steve Horvath,Zsolt Radak
The interaction between nuclear (nDNA) and mitochondrial DNA (mtDNA) methylation is not well known in the healthy population. The D-loop methylation level of the Olympic champions (N = 58) was significantly lower than that of non-champions (N = 32) (~ 36% unadjusted mean difference p = 0.016, sex and age adjusted p = 0.017). Interestingly, the robust linear analysis revealed that biological sex is a significant factor in mtDNA D-loop methylation (estimate = 1.521, p = 0.033). On the other hand, we cannot find relationships between the methylation levels of mtDNA and nuclear DNA, suggesting distinct regulation of the methylation/demethylation process of mtDNA and nuclear DNA. DNA methylation-based aging clocks showed a significant relationship with the levels of Klotho, irisin, and its receptor (irisin receptor integrin alpha-V), as well as with epigenetic regulators such as ten-eleven translocation enzyme 2, which were measured using enzyme-linked immunosorbent assay. Therefore, the data suggest a complex regulatory process of epigenetic aging and raise the possibility that D-loop methylation may have functional relevance in health, which remains to be explored.
在健康人群中,核(nDNA)和线粒体DNA (mtDNA)甲基化之间的相互作用尚不清楚。奥运冠军(N = 58)的D-loop甲基化水平显著低于非奥运冠军(N = 32)(~ 36%未经调整的平均差异p = 0.016,性别和年龄调整p = 0.017)。有趣的是,强有力的线性分析显示,生物性别是mtDNA d -环甲基化的重要因素(估计值= 1.521,p = 0.033)。另一方面,我们没有发现mtDNA和核DNA的甲基化水平之间的关系,这表明mtDNA和核DNA的甲基化/去甲基化过程有不同的调控。基于DNA甲基化的衰老时钟显示与Klotho、鸢尾素及其受体(鸢尾素受体整合素α - v)的水平以及表观遗传调节因子(如10 - 11易位酶2)的水平有显著关系,这些调节因子是用酶联免疫吸附法测量的。因此,这些数据表明表观遗传衰老是一个复杂的调控过程,并提出了d -环甲基化可能在健康中具有功能相关性的可能性,这仍有待探索。
{"title":"Epigenetic insights of Olympic champions: nuclear and mitochondrial DNA methylation and regulators of aging.","authors":"Timea Teglas,Ferenc Torma,Zoltan Bori,Dora Aczel,Gergely Babszky,Takuji Kawamura,Mitsuru Higuchi,Gu Yaodong,Muhammad Lee,Steve Horvath,Zsolt Radak","doi":"10.1007/s11357-025-02092-9","DOIUrl":"https://doi.org/10.1007/s11357-025-02092-9","url":null,"abstract":"The interaction between nuclear (nDNA) and mitochondrial DNA (mtDNA) methylation is not well known in the healthy population. The D-loop methylation level of the Olympic champions (N = 58) was significantly lower than that of non-champions (N = 32) (~ 36% unadjusted mean difference p = 0.016, sex and age adjusted p = 0.017). Interestingly, the robust linear analysis revealed that biological sex is a significant factor in mtDNA D-loop methylation (estimate = 1.521, p = 0.033). On the other hand, we cannot find relationships between the methylation levels of mtDNA and nuclear DNA, suggesting distinct regulation of the methylation/demethylation process of mtDNA and nuclear DNA. DNA methylation-based aging clocks showed a significant relationship with the levels of Klotho, irisin, and its receptor (irisin receptor integrin alpha-V), as well as with epigenetic regulators such as ten-eleven translocation enzyme 2, which were measured using enzyme-linked immunosorbent assay. Therefore, the data suggest a complex regulatory process of epigenetic aging and raise the possibility that D-loop methylation may have functional relevance in health, which remains to be explored.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"29 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145993036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Epigenetic age deceleration reflects exercise-induced cardiorespiratory fitness improvements. 表观遗传年龄减速反映了运动诱导的心肺健康改善。
IF 5.6 2区 医学 Q1 GERIATRICS & GERONTOLOGY Pub Date : 2026-01-17 DOI: 10.1007/s11357-025-02076-9
Menno Van Damme,Sanne Stegen,Bram Steenwinckel,Helene Schroé,Gustavo A Reyes Del Paso,Matias M Pulopulos,Rudi De Raedt,Marie-Anne Vanderhasselt,Wim Derave,Femke Ongenae,Jan Boone,Wim Van Criekinge,Ernst R Rietzschel,Tim De Meyer
Epigenetic clocks are emerging as promising biomarkers of biological aging, yet their sensitivity to short-term interventions remains unclear. This pilot study investigates whether the GrimAge clock can capture the effects of a 6-month cycling-based endurance exercise training intervention, with cardiorespiratory fitness (VO2 max) and body composition as primary outcomes. We enrolled 42 adults aged 35-65, of whom 38 completed the study and 33 adhered to the protocol (> 66% adherence). Participants demonstrated significant improvements in VO2 max (+ 20%, P < 0.001) and body composition (P < 0.001). High-quality epigenetic data preprocessing yielded highly reproducible GrimAge estimates (< 2 months measurement error), which strongly correlated with chronological age (R2 = 0.86, P < 0.001). On average, GrimAge decreased by 7.44 months relative to the expected trajectory (P = 0.012), reflecting improvements in VO2 max (R2 = 0.27, P = 0.002) but not body composition changes. Notably, GrimAge changes strongly correlated with fluctuations in leukocyte composition, particularly neutrophil fraction (R2 = 0.74, P < 0.001). Adjusting for leukocyte composition improved consistency in GrimAge changes, aligning them with additional intervention outcomes and explaining up to 81% of variance. These findings demonstrate that GrimAge is responsive to short-term endurance training, serving as a meaningful biomarker of improved cardiorespiratory fitness, while also capturing immune system variability. This study supports the use of GrimAge in evaluating longevity interventions and highlights the importance of accounting for leukocyte composition in epigenetic aging research.
表观遗传时钟正在成为生物衰老的有前途的生物标志物,但它们对短期干预的敏感性尚不清楚。本初步研究以心肺功能(最大摄氧量)和身体成分为主要指标,调查GrimAge时钟是否能捕捉6个月周期耐力运动训练干预的效果。我们招募了42名年龄在35-65岁之间的成年人,其中38人完成了研究,33人遵守了方案(bbb66%的依从性)。参与者的最大摄氧量(+ 20%,P < 0.001)和身体成分(P < 0.001)均有显著改善。高质量的表观遗传数据预处理产生了高度可重复的GrimAge估计(< 2个月测量误差),其与实足年龄密切相关(R2 = 0.86, P < 0.001)。平均而言,GrimAge相对于预期轨迹减少了7.44个月(P = 0.012),反映了最大摄氧量的改善(R2 = 0.27, P = 0.002),但没有反映身体成分的变化。值得注意的是,GrimAge变化与白细胞组成,特别是中性粒细胞部分的波动密切相关(R2 = 0.74, P < 0.001)。调整白细胞组成提高了GrimAge变化的一致性,使其与其他干预结果一致,并解释了高达81%的差异。这些发现表明GrimAge对短期耐力训练有反应,作为改善心肺健康的有意义的生物标志物,同时也捕获免疫系统变异性。这项研究支持使用GrimAge来评估长寿干预措施,并强调了在表观遗传衰老研究中考虑白细胞组成的重要性。
{"title":"Epigenetic age deceleration reflects exercise-induced cardiorespiratory fitness improvements.","authors":"Menno Van Damme,Sanne Stegen,Bram Steenwinckel,Helene Schroé,Gustavo A Reyes Del Paso,Matias M Pulopulos,Rudi De Raedt,Marie-Anne Vanderhasselt,Wim Derave,Femke Ongenae,Jan Boone,Wim Van Criekinge,Ernst R Rietzschel,Tim De Meyer","doi":"10.1007/s11357-025-02076-9","DOIUrl":"https://doi.org/10.1007/s11357-025-02076-9","url":null,"abstract":"Epigenetic clocks are emerging as promising biomarkers of biological aging, yet their sensitivity to short-term interventions remains unclear. This pilot study investigates whether the GrimAge clock can capture the effects of a 6-month cycling-based endurance exercise training intervention, with cardiorespiratory fitness (VO2 max) and body composition as primary outcomes. We enrolled 42 adults aged 35-65, of whom 38 completed the study and 33 adhered to the protocol (> 66% adherence). Participants demonstrated significant improvements in VO2 max (+ 20%, P < 0.001) and body composition (P < 0.001). High-quality epigenetic data preprocessing yielded highly reproducible GrimAge estimates (< 2 months measurement error), which strongly correlated with chronological age (R2 = 0.86, P < 0.001). On average, GrimAge decreased by 7.44 months relative to the expected trajectory (P = 0.012), reflecting improvements in VO2 max (R2 = 0.27, P = 0.002) but not body composition changes. Notably, GrimAge changes strongly correlated with fluctuations in leukocyte composition, particularly neutrophil fraction (R2 = 0.74, P < 0.001). Adjusting for leukocyte composition improved consistency in GrimAge changes, aligning them with additional intervention outcomes and explaining up to 81% of variance. These findings demonstrate that GrimAge is responsive to short-term endurance training, serving as a meaningful biomarker of improved cardiorespiratory fitness, while also capturing immune system variability. This study supports the use of GrimAge in evaluating longevity interventions and highlights the importance of accounting for leukocyte composition in epigenetic aging research.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"56 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145993035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Microbiota-derived indole-3-propionic acid extends lifespan in Drosophila and improves muscle and bone health in mice. 微生物衍生的吲哚-3-丙酸延长果蝇的寿命,改善小鼠的肌肉和骨骼健康。
IF 5.6 2区 医学 Q1 GERIATRICS & GERONTOLOGY Pub Date : 2026-01-16 DOI: 10.1007/s11357-025-02078-7
Sagar Vyavahare,Ford Berger,Shelton G Swint,Bharati Mendhe,Mansi Shukla,Ian Duchesne,Roger Zhong,Marion A Cooley,Meghan E McGee-Lawrence,Carlos M Isales,Jessica M Hoffman,Sadanand Fulzele
Aging is associated with alterations in endogenous tryptophan (TRP) metabolism that contributes to musculoskeletal decline. In this study, we investigated the effects of the microbiota-derived TRP metabolite, indole-3-propionic acid (IPA), on musculoskeletal health in aged mice and lifespan in Drosophila melanogaster. Aged C57BL/6 mice received IPA (20 mg/kg, subcutaneous, three times per week for 12 weeks), while Drosophila were maintained on food supplemented with IPA (100 µM) throughout their lifespan. Our findings revealed that IPA-treated aged mice exhibited enhanced muscle function (grip strength and hang time). Histological and bone microCT analyses revealed no changes in muscle fiber size but enhanced bone microarchitecture. Furthermore, molecular studies have elucidated that IPA treatment prevents oxidative stress and reduces senescence, indicating improved cellular survival. Our Drosophila melanogaster longevity analysis revealed a significant extension of lifespan, but lifespan effects were genotype- and sex-specific. Collectively, our findings identify IPA as a promising microbiota-derived metabolite that improves musculoskeletal health and promotes longevity, highlighting its potential as a therapeutic intervention for age-related decline in function.
衰老与内源性色氨酸(TRP)代谢的改变有关,从而导致肌肉骨骼衰退。在这项研究中,我们研究了微生物来源的TRP代谢物吲哚-3-丙酸(IPA)对老年小鼠肌肉骨骼健康和黑腹果蝇寿命的影响。老年C57BL/6小鼠给予IPA (20 mg/kg,皮下注射,每周3次,持续12周),果蝇终生喂食添加IPA(100µM)的食物。我们的研究结果显示,ipa处理的老年小鼠表现出增强的肌肉功能(握力和悬挂时间)。组织学和骨微ct分析显示肌纤维大小没有变化,但骨微结构增强。此外,分子研究表明,IPA治疗可以防止氧化应激,减少衰老,表明细胞存活率提高。我们对黑腹果蝇的寿命分析揭示了寿命的显著延长,但寿命效应是基因型和性别特异性的。总的来说,我们的研究结果确定了IPA是一种有前途的微生物衍生代谢物,可以改善肌肉骨骼健康并促进寿命,突出了其作为治疗与年龄相关的功能衰退的干预措施的潜力。
{"title":"Microbiota-derived indole-3-propionic acid extends lifespan in Drosophila and improves muscle and bone health in mice.","authors":"Sagar Vyavahare,Ford Berger,Shelton G Swint,Bharati Mendhe,Mansi Shukla,Ian Duchesne,Roger Zhong,Marion A Cooley,Meghan E McGee-Lawrence,Carlos M Isales,Jessica M Hoffman,Sadanand Fulzele","doi":"10.1007/s11357-025-02078-7","DOIUrl":"https://doi.org/10.1007/s11357-025-02078-7","url":null,"abstract":"Aging is associated with alterations in endogenous tryptophan (TRP) metabolism that contributes to musculoskeletal decline. In this study, we investigated the effects of the microbiota-derived TRP metabolite, indole-3-propionic acid (IPA), on musculoskeletal health in aged mice and lifespan in Drosophila melanogaster. Aged C57BL/6 mice received IPA (20 mg/kg, subcutaneous, three times per week for 12 weeks), while Drosophila were maintained on food supplemented with IPA (100 µM) throughout their lifespan. Our findings revealed that IPA-treated aged mice exhibited enhanced muscle function (grip strength and hang time). Histological and bone microCT analyses revealed no changes in muscle fiber size but enhanced bone microarchitecture. Furthermore, molecular studies have elucidated that IPA treatment prevents oxidative stress and reduces senescence, indicating improved cellular survival. Our Drosophila melanogaster longevity analysis revealed a significant extension of lifespan, but lifespan effects were genotype- and sex-specific. Collectively, our findings identify IPA as a promising microbiota-derived metabolite that improves musculoskeletal health and promotes longevity, highlighting its potential as a therapeutic intervention for age-related decline in function.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"29 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145971849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Metacontrol-related aperiodic and periodic neural activity in cognitive aging: enhancing the neural signal-to-noise ratio through anodal transcranial direct current stimulation. 认知老化中与元控制相关的非周期性和周期性神经活动:通过阳极经颅直流电刺激增强神经信噪比。
IF 5.6 2区 医学 Q1 GERIATRICS & GERONTOLOGY Pub Date : 2026-01-16 DOI: 10.1007/s11357-025-02077-8
Yu Pi,Qinfei Zhang,Shuhui Lyu,Christian Beste,Lorenza Colzato,Bernhard Hommel
Metacontrol, the ability to adapt cognitive control to task demands, declines with age and is thought to be reflected in aperiodic and periodic neural dynamics. Given that anodal transcranial direct current stimulation (atDCS) can modulate cortical excitability via membrane potential shifts, we tested whether atDCS alters the neurophysiological signatures of metacontrol in younger and older adults. In a mixed design, younger and older participants performed a Go/Nogo task under both atDCS and sham stimulation conditions; resting-state EEG data were also acquired. Aperiodic activity was analyzed using the FOOOF algorithm, and periodic activity was examined through time-frequency analysis. Behaviorally, younger adults showed higher accuracy and faster responses than older adults, but no significant stimulation effects emerged in either group. Results showed that, compared to sham, aperiodic activity (FOOOF exponent) increased after atDCS, particularly in older adults, indicating a steepening of the EEG spectrum and thus increased inhibitory tone in the aging process. However, resting-state aperiodic activity did not predict stimulation-induced effects within either group. In the periodic domain, we found no evidence that atDCS modulated task-related theta or alpha power. Moreover, exploratory analyses revealed no significant associations between atDCS-induced changes in the aperiodic exponent and oscillatory power. This dissociation indicates that, under the present conditions, the periodic and aperiodic components of the EEG signal reflect distinct and likely independent neurophysiological responses to neuromodulation. Targeting metacontrol mechanisms through neuromodulation may, with further validation, open new avenues for supporting cognitive health in older adults.
元控制,即适应任务需求的认知控制能力,随着年龄的增长而下降,被认为反映在非周期性和周期性的神经动力学中。考虑到阳极经颅直流电刺激(atDCS)可以通过膜电位转移调节皮质兴奋性,我们测试了atDCS是否会改变年轻人和老年人元控制的神经生理特征。在混合设计中,年轻和年长的参与者在atDCS和假刺激条件下都执行Go/Nogo任务;静息状态脑电数据采集。利用FOOOF算法分析非周期活度,通过时频分析分析周期活度。在行为上,年轻人比老年人表现出更高的准确性和更快的反应,但两组都没有明显的刺激效应。结果显示,与假手术相比,atDCS后非周期活动(FOOOF指数)增加,特别是在老年人中,表明脑电图谱变陡,从而增加了衰老过程中的抑制性张力。然而,静息状态的非周期活动并不能预测两组的刺激诱导效应。在周期域中,我们没有发现atDCS调制与任务相关的θ或α功率的证据。此外,探索性分析显示,atdcs诱导的非周期指数变化与振荡功率之间没有显着关联。这种分离表明,在目前的条件下,脑电图信号的周期性和非周期性成分反映了不同的和可能独立的神经生理反应。通过神经调节靶向元控制机制,进一步验证,为支持老年人的认知健康开辟了新的途径。
{"title":"Metacontrol-related aperiodic and periodic neural activity in cognitive aging: enhancing the neural signal-to-noise ratio through anodal transcranial direct current stimulation.","authors":"Yu Pi,Qinfei Zhang,Shuhui Lyu,Christian Beste,Lorenza Colzato,Bernhard Hommel","doi":"10.1007/s11357-025-02077-8","DOIUrl":"https://doi.org/10.1007/s11357-025-02077-8","url":null,"abstract":"Metacontrol, the ability to adapt cognitive control to task demands, declines with age and is thought to be reflected in aperiodic and periodic neural dynamics. Given that anodal transcranial direct current stimulation (atDCS) can modulate cortical excitability via membrane potential shifts, we tested whether atDCS alters the neurophysiological signatures of metacontrol in younger and older adults. In a mixed design, younger and older participants performed a Go/Nogo task under both atDCS and sham stimulation conditions; resting-state EEG data were also acquired. Aperiodic activity was analyzed using the FOOOF algorithm, and periodic activity was examined through time-frequency analysis. Behaviorally, younger adults showed higher accuracy and faster responses than older adults, but no significant stimulation effects emerged in either group. Results showed that, compared to sham, aperiodic activity (FOOOF exponent) increased after atDCS, particularly in older adults, indicating a steepening of the EEG spectrum and thus increased inhibitory tone in the aging process. However, resting-state aperiodic activity did not predict stimulation-induced effects within either group. In the periodic domain, we found no evidence that atDCS modulated task-related theta or alpha power. Moreover, exploratory analyses revealed no significant associations between atDCS-induced changes in the aperiodic exponent and oscillatory power. This dissociation indicates that, under the present conditions, the periodic and aperiodic components of the EEG signal reflect distinct and likely independent neurophysiological responses to neuromodulation. Targeting metacontrol mechanisms through neuromodulation may, with further validation, open new avenues for supporting cognitive health in older adults.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"4 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145986575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Lipid-laden endothelial cells exhibit a transcriptomic signature linked to blood-brain barrier dysfunction, metabolic reprogramming, and increased inflammation in the aging brain. 脂质内皮细胞表现出与血脑屏障功能障碍、代谢重编程和老化大脑中炎症增加有关的转录组特征。
IF 5.4 2区 医学 Q1 GERIATRICS & GERONTOLOGY Pub Date : 2026-01-16 DOI: 10.1007/s11357-025-01986-y
Sarah Otu-Boakye, Duraipandy Natarajan, Bhuvana Plakkot, Ilakiya Raghavendiran, Paulina Hoppa, Tamas Kiss, Madhan Subramanian, Priya Balasubramanian

Dysregulation in lipid metabolism is increasingly recognized as a key contributor to age-related diseases, including neurodegeneration and cerebrovascular dysfunction. While prior studies have largely focused on glial cells, the impact of lipid dysregulation on brain endothelial aging remains poorly understood. In this study, we conducted a secondary analysis of single-cell transcriptomic data from young and aged mouse brains, with a specific focus on endothelial cells (ECs). Our analyses revealed that aging promotes lipid droplet accumulation in brain ECs. These lipid-laden brain ECs exhibit a transcriptomic signature indicative of impaired blood-brain barrier function, increased cellular senescence, and inflammation in aging. Furthermore, lipid accumulation is associated with an altered metabolic phenotype characterized by increased fatty acid oxidation and decreased glycolysis and impaired mitochondrial electron transport chain activity in the ECs of the aging brain. We have also validated lipid accumulation in aged ECs in vivo. Collectively, our findings indicate that lipid accumulation may drive structural, functional, and metabolic impairments in the brain ECs, likely contributing to cerebrovascular aging. Understanding the mechanisms underlying lipid accumulation-induced endothelial dysfunction may offer novel therapeutic strategies for mitigating microvascular dysfunction and cognitive decline in aging.

脂质代谢失调越来越被认为是与年龄有关的疾病的关键因素,包括神经变性和脑血管功能障碍。虽然先前的研究主要集中在神经胶质细胞上,但脂质失调对脑内皮细胞衰老的影响仍然知之甚少。在这项研究中,我们对来自年轻和老年小鼠大脑的单细胞转录组数据进行了二次分析,特别关注内皮细胞(ECs)。我们的分析表明,衰老促进了脑内皮细胞中脂滴的积累。这些富含脂质的脑ECs表现出一种转录组学特征,表明血脑屏障功能受损、细胞衰老加剧和衰老过程中的炎症。此外,脂质积累与代谢表型的改变有关,其特征是脂肪酸氧化增加,糖酵解减少,衰老大脑ec中线粒体电子传递链活性受损。我们还在体内验证了老年内皮细胞的脂质积累。总的来说,我们的研究结果表明,脂质积累可能会导致脑ECs的结构、功能和代谢损伤,可能导致脑血管老化。了解脂质积累诱导的内皮功能障碍的机制可能为减轻微血管功能障碍和衰老的认知能力下降提供新的治疗策略。
{"title":"Lipid-laden endothelial cells exhibit a transcriptomic signature linked to blood-brain barrier dysfunction, metabolic reprogramming, and increased inflammation in the aging brain.","authors":"Sarah Otu-Boakye, Duraipandy Natarajan, Bhuvana Plakkot, Ilakiya Raghavendiran, Paulina Hoppa, Tamas Kiss, Madhan Subramanian, Priya Balasubramanian","doi":"10.1007/s11357-025-01986-y","DOIUrl":"10.1007/s11357-025-01986-y","url":null,"abstract":"<p><p>Dysregulation in lipid metabolism is increasingly recognized as a key contributor to age-related diseases, including neurodegeneration and cerebrovascular dysfunction. While prior studies have largely focused on glial cells, the impact of lipid dysregulation on brain endothelial aging remains poorly understood. In this study, we conducted a secondary analysis of single-cell transcriptomic data from young and aged mouse brains, with a specific focus on endothelial cells (ECs). Our analyses revealed that aging promotes lipid droplet accumulation in brain ECs. These lipid-laden brain ECs exhibit a transcriptomic signature indicative of impaired blood-brain barrier function, increased cellular senescence, and inflammation in aging. Furthermore, lipid accumulation is associated with an altered metabolic phenotype characterized by increased fatty acid oxidation and decreased glycolysis and impaired mitochondrial electron transport chain activity in the ECs of the aging brain. We have also validated lipid accumulation in aged ECs in vivo. Collectively, our findings indicate that lipid accumulation may drive structural, functional, and metabolic impairments in the brain ECs, likely contributing to cerebrovascular aging. Understanding the mechanisms underlying lipid accumulation-induced endothelial dysfunction may offer novel therapeutic strategies for mitigating microvascular dysfunction and cognitive decline in aging.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145989201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
期刊
GeroScience
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1