Pub Date : 2026-01-28DOI: 10.1007/s11357-026-02110-4
Thole H Hoppen,Nexhmedin Morina,Monica Aas,Julian Mutz
Exposure to non-relational trauma, such as serious accidents, war or life-threatening illness, is linked to poor mental and physical health. Its relationship with biological ageing markers, however, remains underexplored. This study's aim was to examine associations between non-relational trauma and multiple biological ageing markers, and to assess whether associations vary by trauma burden, trauma type and sex. We analysed UK Biobank data from 152,863 participants (mean age = 56.4 years; 56.5% female). Lifetime exposure to six non-relational traumatic experiences was assessed. Biological ageing markers included metabolomic age (MileAge) delta, a metabolomic mortality profile score, frailty, leukocyte telomere length and grip strength. Regression models, adjusted for demographic and socioeconomic confounders, estimated associations between trauma and biological ageing markers. We also examined trauma burden, trauma type-specific and sex-specific associations. Non-relational trauma was associated with a metabolite-predicted age exceeding chronological age (MileAge delta; β = 0.047, 95% CI 0.032-0.062), elevated metabolomic mortality scores (β = 0.102, 95% CI 0.051-0.153) and greater frailty (β = 0.298, 95% CI 0.290-0.307), with a graded, approximately linear pattern for frailty (i.e., higher non-relational trauma sum scores were associated with higher frailty scores). All trauma types were associated with greater frailty, with the strongest association for life-threatening illness. There was no evidence of associations with telomere length, and mixed findings for grip strength. Several associations differed by sex, for example overall trauma burden was more strongly associated with greater frailty in females compared to males. Lifetime non-relational trauma was associated with older biological ageing profiles, with the strongest associations with frailty. These findings support the notion that non-relational trauma exposure is associated with long-term health status, underscoring the need for mitigating ageing-related health decline in trauma-exposed populations.
遭受非关系性创伤，如严重事故、战争或危及生命的疾病，与精神和身体健康状况不佳有关。然而，它与生物衰老标志物的关系仍未得到充分探索。本研究的目的是研究非关系性创伤与多种生物衰老标志物之间的联系，并评估这种联系是否因创伤负担、创伤类型和性别而异。我们分析了英国生物银行152,863名参与者（平均年龄56.4岁，56.5%为女性）的数据。评估了六种非关系性创伤经历的终生暴露。生物老化标志物包括代谢组年龄（里程）delta、代谢组死亡率谱评分、虚弱、白细胞端粒长度和握力。根据人口统计学和社会经济混杂因素调整的回归模型估计了创伤和生物衰老标志物之间的关联。我们还研究了创伤负担、创伤类型特异性和性别特异性的关联。非关系性创伤与代谢预测年龄超过实际年龄（里程δ； β = 0.047, 95% CI 0.032-0.062）、代谢组学死亡率评分升高（β = 0.102, 95% CI 0.051-0.153）和更大的虚弱（β = 0.298, 95% CI 0.290-0.307）相关，虚弱呈分级近似线性模式（即，较高的非关系性创伤总评分与较高的虚弱评分相关）。所有的创伤类型都与更大的虚弱有关，与危及生命的疾病的联系最为密切。没有证据表明与端粒长度有关，握力也有不同的结果。一些关联因性别而异，例如，与男性相比，女性的总体创伤负担与更大的脆弱性联系更紧密。终生非关系性创伤与较老的生物老化特征有关，与脆弱的联系最为密切。这些发现支持了非关系性创伤暴露与长期健康状况相关的观点，强调了减轻创伤暴露人群中与年龄相关的健康下降的必要性。
{"title":"Lifetime non-relational traumatic experiences are associated with biological ageing.","authors":"Thole H Hoppen,Nexhmedin Morina,Monica Aas,Julian Mutz","doi":"10.1007/s11357-026-02110-4","DOIUrl":"https://doi.org/10.1007/s11357-026-02110-4","url":null,"abstract":"Exposure to non-relational trauma, such as serious accidents, war or life-threatening illness, is linked to poor mental and physical health. Its relationship with biological ageing markers, however, remains underexplored. This study's aim was to examine associations between non-relational trauma and multiple biological ageing markers, and to assess whether associations vary by trauma burden, trauma type and sex. We analysed UK Biobank data from 152,863 participants (mean age = 56.4 years; 56.5% female). Lifetime exposure to six non-relational traumatic experiences was assessed. Biological ageing markers included metabolomic age (MileAge) delta, a metabolomic mortality profile score, frailty, leukocyte telomere length and grip strength. Regression models, adjusted for demographic and socioeconomic confounders, estimated associations between trauma and biological ageing markers. We also examined trauma burden, trauma type-specific and sex-specific associations. Non-relational trauma was associated with a metabolite-predicted age exceeding chronological age (MileAge delta; β = 0.047, 95% CI 0.032-0.062), elevated metabolomic mortality scores (β = 0.102, 95% CI 0.051-0.153) and greater frailty (β = 0.298, 95% CI 0.290-0.307), with a graded, approximately linear pattern for frailty (i.e., higher non-relational trauma sum scores were associated with higher frailty scores). All trauma types were associated with greater frailty, with the strongest association for life-threatening illness. There was no evidence of associations with telomere length, and mixed findings for grip strength. Several associations differed by sex, for example overall trauma burden was more strongly associated with greater frailty in females compared to males. Lifetime non-relational trauma was associated with older biological ageing profiles, with the strongest associations with frailty. These findings support the notion that non-relational trauma exposure is associated with long-term health status, underscoring the need for mitigating ageing-related health decline in trauma-exposed populations.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"42 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056511","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}
Pub Date : 2026-01-28DOI: 10.1007/s11357-026-02103-3
Tianhao Wu,Chengnan Guo,Huangbo Yuan,Mingyi Du,Tiejun Zhang,Xingdong Chen,Zhenqiu Liu
Phenotypic age, an aging indicator derived from clinical biomarkers, is associated with morbidities and mortality. However, a liver-specific phenotypic aging indicator is still lacking, and its longitudinal associations with liver-related outcomes, as well as the underlying biological mechanisms, remain elusive. We developed a liver-specific phenotypic age using 11 selected clinical blood markers within the England-White cohort of the UK Biobank and validated this metric in both the Scotland-Wales cohort and Non-White-British cohort. We calculated phenotypic age acceleration (PhenoAgeAccel) and examined its association with long-term liver-related outcomes. We also explored the extent to which liver-specific PhenoAgeAccel mediated the impact of modifiable risk behaviors on liver-related outcomes. The metabolic and proteomic signatures of liver-specific PhenoAgeAccel were subsequently characterized. Liver-specific PhenoAgeAccel was significantly associated with a 1.23- to 2.97-fold increased risks of all-cause mortality and liver-related events. The impact of liver-specific PhenoAgeAccel on liver outcomes were more pronounced in males and in individuals with high genetic risk compared to their respective counterparts, and was stronger than that observed with systemic PhenoAgeAccel. Approximately 10-27% of the associations between risk behaviors and liver-related outcomes were mediated by liver-specific PhenoAgeAccel. Proteomic analysis identified 211 proteins associated with both liver-specific PhenoAgeAccel and liver-related outcomes, of which 22 (e.g., AGXT and SULT2A1) were liver-enriched and significantly mediated this relationship. Liver-specific PhenoAgeAccel is a strong predictor of liver-related outcomes, partially mediates the impact of modifiable behaviors, and is linked to liver-enriched proteins. This accessible tool may enhance risk stratification and support preventive strategies targeting liver health and aging.
{"title":"Liver-specific phenotypic aging, behavior and genetic risks, and long-term liver-related outcomes.","authors":"Tianhao Wu,Chengnan Guo,Huangbo Yuan,Mingyi Du,Tiejun Zhang,Xingdong Chen,Zhenqiu Liu","doi":"10.1007/s11357-026-02103-3","DOIUrl":"https://doi.org/10.1007/s11357-026-02103-3","url":null,"abstract":"Phenotypic age, an aging indicator derived from clinical biomarkers, is associated with morbidities and mortality. However, a liver-specific phenotypic aging indicator is still lacking, and its longitudinal associations with liver-related outcomes, as well as the underlying biological mechanisms, remain elusive. We developed a liver-specific phenotypic age using 11 selected clinical blood markers within the England-White cohort of the UK Biobank and validated this metric in both the Scotland-Wales cohort and Non-White-British cohort. We calculated phenotypic age acceleration (PhenoAgeAccel) and examined its association with long-term liver-related outcomes. We also explored the extent to which liver-specific PhenoAgeAccel mediated the impact of modifiable risk behaviors on liver-related outcomes. The metabolic and proteomic signatures of liver-specific PhenoAgeAccel were subsequently characterized. Liver-specific PhenoAgeAccel was significantly associated with a 1.23- to 2.97-fold increased risks of all-cause mortality and liver-related events. The impact of liver-specific PhenoAgeAccel on liver outcomes were more pronounced in males and in individuals with high genetic risk compared to their respective counterparts, and was stronger than that observed with systemic PhenoAgeAccel. Approximately 10-27% of the associations between risk behaviors and liver-related outcomes were mediated by liver-specific PhenoAgeAccel. Proteomic analysis identified 211 proteins associated with both liver-specific PhenoAgeAccel and liver-related outcomes, of which 22 (e.g., AGXT and SULT2A1) were liver-enriched and significantly mediated this relationship. Liver-specific PhenoAgeAccel is a strong predictor of liver-related outcomes, partially mediates the impact of modifiable behaviors, and is linked to liver-enriched proteins. This accessible tool may enhance risk stratification and support preventive strategies targeting liver health and aging.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"293 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056875","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}
Pub Date : 2026-01-24DOI: 10.1007/s11357-025-02091-w
Barbara Cazzolli,Andrea Chirico,Federica Stefanelli,Michele Zacchilli,Elisa Cavicchiolo,Fabio Alivernini,Fabio Lucidi
Physical and cognitive interventions, alone or combined, are recognized strategies to enhance cognitive function in healthy older adults, though their relative effectiveness remains debated. This study aimed to compare and classify the impact of such interventions on cognitive performance. Following PRISMA guidelines, randomized controlled trials (RCTs) were identified through searches of PubMed, Web of Science, and Scopus, with screening and data extraction procedures guided by the Cochrane Handbook for Systematic Reviews of Interventions. The protocol was registered on PROSPERO (CRD42024565879). A network meta-analysis synthesized results from 87 studies including participants aged 65 and older. Interventions were grouped into seven groups, covering dual-task, single-task, technology-based formats, and a control group. Compared with controls, cognitive-motor dual-task training showed the strongest effects (SMD = 0.71, 95% CI 0.45, 0.97). Differences between exercise types were not statistically significant. However, dual-task approaches, whether technology-supported or not, outperformed traditional physical training (e.g., SMD = 0.33, 95% CI 0.05, 0.61). Findings suggest that dual-task interventions effectively enhance cognitive performance, with technology adding value by creating engaging and adaptive experiences. Technology particularly strengthened single-task training. Future research should examine specific executive functions and scalable technology-based methods to guide evidence-based strategies that promote healthy aging and cognitive resilience.
身体和认知干预，单独或联合，是公认的提高健康老年人认知功能的策略，尽管它们的相对有效性仍存在争议。本研究旨在比较和分类这些干预措施对认知表现的影响。遵循PRISMA指南，随机对照试验（rct）通过PubMed、Web of Science和Scopus检索确定，筛选和数据提取程序由Cochrane干预措施系统评价手册指导。该协议在PROSPERO上注册（CRD42024565879）。一项网络荟萃分析综合了87项研究的结果，其中包括65岁及以上的参与者。干预措施分为七组，包括双任务、单任务、基于技术的格式和对照组。与对照组相比，认知-运动双任务训练效果最强（SMD = 0.71, 95% CI 0.45, 0.97）。不同运动类型之间的差异无统计学意义。然而，无论是否有技术支持，双任务方法都优于传统的体育训练（例如，SMD = 0.33, 95% CI 0.05, 0.61）。研究结果表明，双重任务干预有效地提高了认知表现，技术通过创造参与和适应性体验来增加价值。技术特别加强了单任务训练。未来的研究应检查具体的执行功能和可扩展的基于技术的方法，以指导以证据为基础的战略，促进健康老龄化和认知弹性。
{"title":"Optimizing cognitive functions in healthy older adults: a network meta-analysis of dual- and single-task interventions.","authors":"Barbara Cazzolli,Andrea Chirico,Federica Stefanelli,Michele Zacchilli,Elisa Cavicchiolo,Fabio Alivernini,Fabio Lucidi","doi":"10.1007/s11357-025-02091-w","DOIUrl":"https://doi.org/10.1007/s11357-025-02091-w","url":null,"abstract":"Physical and cognitive interventions, alone or combined, are recognized strategies to enhance cognitive function in healthy older adults, though their relative effectiveness remains debated. This study aimed to compare and classify the impact of such interventions on cognitive performance. Following PRISMA guidelines, randomized controlled trials (RCTs) were identified through searches of PubMed, Web of Science, and Scopus, with screening and data extraction procedures guided by the Cochrane Handbook for Systematic Reviews of Interventions. The protocol was registered on PROSPERO (CRD42024565879). A network meta-analysis synthesized results from 87 studies including participants aged 65 and older. Interventions were grouped into seven groups, covering dual-task, single-task, technology-based formats, and a control group. Compared with controls, cognitive-motor dual-task training showed the strongest effects (SMD = 0.71, 95% CI 0.45, 0.97). Differences between exercise types were not statistically significant. However, dual-task approaches, whether technology-supported or not, outperformed traditional physical training (e.g., SMD = 0.33, 95% CI 0.05, 0.61). Findings suggest that dual-task interventions effectively enhance cognitive performance, with technology adding value by creating engaging and adaptive experiences. Technology particularly strengthened single-task training. Future research should examine specific executive functions and scalable technology-based methods to guide evidence-based strategies that promote healthy aging and cognitive resilience.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"85 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146042468","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}
Pub Date : 2026-01-24DOI: 10.1007/s11357-026-02098-x
May A Beydoun,Tianyi Huang,Nicole Noren Hooten,Hind A Beydoun,Mustapha Bouhrara,Jordan Weiss,Michele K Evans,Alan B Zonderman
Red cell distribution width (RDW), reflecting erythrocyte size variability, and serum vitamin D are emerging biomarkers for dementia. We examined the independent and joint associations of RDW and 25-hydroxyvitamin D [25(OH)D] with incident dementia and the potential mediating role of plasma metabolomic profiles in a large prospective cohort study. We analyzed data from 162,606 UK Biobank participants aged ≥ 50 years and dementia-free with RDW and 25(OH)D measurements at baseline. Incident dementia was identified via electronic health records for ≤ 15 years. Cox proportional hazards models adjusted for sociodemographic, cardiovascular, and genetic factors. Mediation was assessed using generalized structural equation models based on 15 metabolomic principal components (zMETAB1-zMETAB15) derived from 249 NMR-based plasma metabolites. Higher RDW was associated with increased dementia risk (HR = 1.05; 95% CI: 1.02-1.08) and a atherogenic lipid signature (zMETAB1: Cholesteryl Esters in VLDL), while higher 25(OH)D was associated with lower risk (HR = 0.89; 95% CI: 0.86-0.92) and more favorable metabolomic profiles (zMETAB7: higher Omega-3 Fatty Acids; zMETAB12: lower Saturated Fatty Acids). zMETAB1, zMETAB2 (Free Cholesterol in Small HDL), and zMETAB4 (Phospholipids in Small HDL) significantly mediated RDW's effect on dementia (up to 8.8%), whereas ~ 10.8% of the association with vitamin D was mediated by zMETAB1, with additional contributions from zMETAB7 and zMETAB12. Omega-3 fatty acids partially mediated both associations, while RDW and 25(OH)D did not interact significantly in relation to dementia risk. RDW and vitamin D exert opposing, non-interactive influences on dementia risk. Lipid metabolism, particularly omega-3 fatty acids, partially mediates both associations, highlighting a common metabolic pathway that could be targeted for prevention. These findings suggest that interventions aimed at increasing omega-3 intake may simultaneously modulate the effects of both RDW and vitamin D on dementia risk, offering a promising translational strategy for early risk reduction.
{"title":"Metabolic signatures, vitamin D, and red cell distribution width in dementia risk: UK Biobank insights.","authors":"May A Beydoun,Tianyi Huang,Nicole Noren Hooten,Hind A Beydoun,Mustapha Bouhrara,Jordan Weiss,Michele K Evans,Alan B Zonderman","doi":"10.1007/s11357-026-02098-x","DOIUrl":"https://doi.org/10.1007/s11357-026-02098-x","url":null,"abstract":"Red cell distribution width (RDW), reflecting erythrocyte size variability, and serum vitamin D are emerging biomarkers for dementia. We examined the independent and joint associations of RDW and 25-hydroxyvitamin D [25(OH)D] with incident dementia and the potential mediating role of plasma metabolomic profiles in a large prospective cohort study. We analyzed data from 162,606 UK Biobank participants aged ≥ 50 years and dementia-free with RDW and 25(OH)D measurements at baseline. Incident dementia was identified via electronic health records for ≤ 15 years. Cox proportional hazards models adjusted for sociodemographic, cardiovascular, and genetic factors. Mediation was assessed using generalized structural equation models based on 15 metabolomic principal components (zMETAB1-zMETAB15) derived from 249 NMR-based plasma metabolites. Higher RDW was associated with increased dementia risk (HR = 1.05; 95% CI: 1.02-1.08) and a atherogenic lipid signature (zMETAB1: Cholesteryl Esters in VLDL), while higher 25(OH)D was associated with lower risk (HR = 0.89; 95% CI: 0.86-0.92) and more favorable metabolomic profiles (zMETAB7: higher Omega-3 Fatty Acids; zMETAB12: lower Saturated Fatty Acids). zMETAB1, zMETAB2 (Free Cholesterol in Small HDL), and zMETAB4 (Phospholipids in Small HDL) significantly mediated RDW's effect on dementia (up to 8.8%), whereas ~ 10.8% of the association with vitamin D was mediated by zMETAB1, with additional contributions from zMETAB7 and zMETAB12. Omega-3 fatty acids partially mediated both associations, while RDW and 25(OH)D did not interact significantly in relation to dementia risk. RDW and vitamin D exert opposing, non-interactive influences on dementia risk. Lipid metabolism, particularly omega-3 fatty acids, partially mediates both associations, highlighting a common metabolic pathway that could be targeted for prevention. These findings suggest that interventions aimed at increasing omega-3 intake may simultaneously modulate the effects of both RDW and vitamin D on dementia risk, offering a promising translational strategy for early risk reduction.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"31 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033685","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}
Pub Date : 2026-01-23DOI: 10.1007/s11357-026-02102-4
Shanshan Ran,Jingyi Zhang,Miao Cai,Lan Chen,Zhengmin Qian,Fei Tian,Gan Wu,Ri'enna Boyd,Stephen Edward McMillin,Huai-Cai Zeng,Yin Yang,Hualiang Lin
BACKGROUNDAir pollution is associated with Alzheimer's disease (AD), and the susceptibility of AD from air pollution may be affected by genetic characteristics, but the underlying mechanisms remain unknown.METHODSData from the UK Biobank, in conjunction with PLINK2, was utilized to conduct a genome-wide analysis of a gene-air pollution (PM2.5, PM10, NO2, and NOx) interaction in AD. Functional annotation, positional gene mapping, expression Quantitative Trait Loci (eQTL) analysis, 3D chromatin interactions mapping (ciMap), and gene expression analysis were conducted using FUMA. Potential biological pathways was analyzed by Metascape.RESULTSA total of 322,958 participants were included in the study. Genome-wide gene-air pollution interaction analysis (GWIA) identified 38, 36, 66, and 101 genomic risk loci that interacted with PM2.5, PM10, NO2 and NOx (p < 5 × 10-8). The functional annotation positional gene mapping, eQTL, ciMap mapping, and quantitative gene prioritization prioritized 26, 25, 46 and 70 prioritized genes for PM2.5, PM10, NO2 and NOx, including PTCH1, UNC80, TUBGCP3, RUNX2, RCAN2, SUPT3H, DNPH1, TTBK1, and RSPH9, and we found significantly high expression of NOx-related prioritized genes in the heart atrial appendage, the modulation of smoothened signaling was associated with PM2.5 and PM10, hemopoiesis was associated with nitrogen oxides, and learning or memory processes may be involved in the interaction between PM2.5, NO2, NOx, and genes, affecting Alzheimer's disease.CONCLUSIONSWe prioritized genetic risk loci that interact with air pollutants in AD and revealed that learning or memory are crucial pathways through which these pollutants interact with genes PDE1B, SRF, ZNF385A, and TTBK1.
{"title":"Associations of air pollution and genetic risk and their interaction with risk of Alzheimer's disease: identification of risk loci and potential biological pathways.","authors":"Shanshan Ran,Jingyi Zhang,Miao Cai,Lan Chen,Zhengmin Qian,Fei Tian,Gan Wu,Ri'enna Boyd,Stephen Edward McMillin,Huai-Cai Zeng,Yin Yang,Hualiang Lin","doi":"10.1007/s11357-026-02102-4","DOIUrl":"https://doi.org/10.1007/s11357-026-02102-4","url":null,"abstract":"BACKGROUNDAir pollution is associated with Alzheimer's disease (AD), and the susceptibility of AD from air pollution may be affected by genetic characteristics, but the underlying mechanisms remain unknown.METHODSData from the UK Biobank, in conjunction with PLINK2, was utilized to conduct a genome-wide analysis of a gene-air pollution (PM2.5, PM10, NO2, and NOx) interaction in AD. Functional annotation, positional gene mapping, expression Quantitative Trait Loci (eQTL) analysis, 3D chromatin interactions mapping (ciMap), and gene expression analysis were conducted using FUMA. Potential biological pathways was analyzed by Metascape.RESULTSA total of 322,958 participants were included in the study. Genome-wide gene-air pollution interaction analysis (GWIA) identified 38, 36, 66, and 101 genomic risk loci that interacted with PM2.5, PM10, NO2 and NOx (p < 5 × 10-8). The functional annotation positional gene mapping, eQTL, ciMap mapping, and quantitative gene prioritization prioritized 26, 25, 46 and 70 prioritized genes for PM2.5, PM10, NO2 and NOx, including PTCH1, UNC80, TUBGCP3, RUNX2, RCAN2, SUPT3H, DNPH1, TTBK1, and RSPH9, and we found significantly high expression of NOx-related prioritized genes in the heart atrial appendage, the modulation of smoothened signaling was associated with PM2.5 and PM10, hemopoiesis was associated with nitrogen oxides, and learning or memory processes may be involved in the interaction between PM2.5, NO2, NOx, and genes, affecting Alzheimer's disease.CONCLUSIONSWe prioritized genetic risk loci that interact with air pollutants in AD and revealed that learning or memory are crucial pathways through which these pollutants interact with genes PDE1B, SRF, ZNF385A, and TTBK1.","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":"146021612","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}
Pub Date : 2026-01-23DOI: 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.
{"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}
Pub Date : 2026-01-22DOI: 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.
{"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}
Pub Date : 2026-01-21DOI: 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}
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.
{"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}
Pub Date : 2026-01-19DOI: 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}
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