GeroScience最新文献

{"title":"Capturing silent oxidative stress in early Alzheimer's disease: prediction of CSF biomarkers from sleep qEEG data.","authors":"Anna Michela Gaeta, Lorena Gallego Viñarás, Ferran Barbé, Pablo Martínez Olmos, Reinald Pamplona, Farida Dakterzada, Arrate Muñoz-Barrutia, Gerard Piñol-Ripoll","doi":"10.1007/s11357-026-02133-x","DOIUrl":"10.1007/s11357-026-02133-x","url":null,"abstract":"<p><p>Oxidative stress is a central pathogenic process in the earliest stages of Alzheimer's disease (AD), promoting non-enzymatic protein modifications that accumulate in cerebrospinal fluid (CSF) before measurable neurodegeneration. These alterations impair proteostasis and disrupt sleep-regulating neural circuits, producing characteristic changes in sleep electroencephalographic patterns. Because CSF sampling is invasive, quantitative electroencephalography (qEEG) has emerged as a promising non-invasive proxy for early oxidative processes. Here, we investigated whether nonlinear and time-domain sleep qEEG features can estimate CSF oxidative stress biomarkers in early AD using machine learning (ML) models. Forty-two mild-to-moderate AD patients underwent overnight polysomnography, from which sleep qEEG features were extracted. CSF protein oxidation biomarkers-glutamic semialdehyde, aminoadipic semialdehyde, N-carboxyethyl-lysine, N-carboxymethyl-lysine, and N-malondialdehyde-lysine-were quantified by gas chromatography/mass spectrometry, and ML models were trained to predict CSF biomarker levels from qEEG features. The best-performing model was a random forest trained on the first principal component, achieving an <math><msup><mi>R</mi> <mn>2</mn></msup> </math> of 0.625 and a mean absolute error (MAE) of 467.1 pg/mL. Features derived from frontal and central electrodes during slow-wave sleep and rapid eye movement sleep contributed most strongly to predictive performance. Predictions for healthy controls displayed distributions distinct from those of AD patients, supporting the biological specificity of the qEEG-based estimates. These exploratory analyses suggest that sleep qEEG combined with ML can noninvasively capture silent oxidative processes involved early in AD pathological cascades, with potential for risk stratification, disease monitoring, and non-invasive upstream biomarkers development.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"8467-8490"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146179111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mediating role of muscle strength and body composition on the association between movement behaviours and health-related quality of life in Spanish older adults: the IMPACT65 + study.","authors":"Julia Wiedmaier-Barros, Sara Higueras-Fresnillo, Kabir P Sadarangani, Verónica Cabanas-Sánchez, David Martínez-Gómez","doi":"10.1007/s11357-026-02121-1","DOIUrl":"10.1007/s11357-026-02121-1","url":null,"abstract":"<p><p>Physical activity can improve health-related quality of life (HRQoL); however, it is not clear whether this association is direct or indirect. The aims of this study were to examine the associations of daily movement behaviours with physical and mental HRQoL in older adults, and the mediating role of muscle strength and body composition on it. Three hundred thirty-four community-dwelling older adults wore the Intelligent Device for Energy Expenditure and Activity for two consecutive days to quantify time spent in sedentary behaviour (SB), light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA). HRQoL was assessed using the 12-Item Short-Form Health Survey, yielding physical (PCS) and mental (MCS) component scores. For muscle strength, a handgrip dynamometer and the Sit-to-Stand test were used. Body mass index (BMI), waist circumference, and estimates of skeletal muscle mass and fat mass by bioelectrical impedance were included as body composition variables. Association analyses were examined using linear regression models, and for mediation analysis, structural equation modelling was used. MVPA was positively associated with PCS [β (95%CI): 0.39 (0.19, 0.59)], whereas no significant associations were observed between MVPA, LPA, or SB and MCS. The association between MVPA and PCS was partially mediated by lower-limb muscle strength and fat mass percentage [8.5% (z = 1.753, p = 0.080) and 28.9% (z = 1.912, p = 0.056), respectively], and fully mediated by skeletal muscle mass normalized by BMI [28.2% (z = 2.016, p = 0.044)].Regular engagement in MVPA is positively associated with the physical component of HRQoL in older adults, both directly and indirectly through muscle strength and skeletal muscle mass.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"8609-8620"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146226536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic frailty trajectories and risk of age-related macular degeneration: a prospective cohort study in UK Biobank.","authors":"Yu Peng, Yuzhou Zhang, Ka Wai Kam, Mary Ho, Simon Sezto, Sunny Au, Charlene C Yim, Xiujuan Zhang, Mandy P H Ng, Patrick Ip, Alvin Young, Chi Pui Pang, Clement C Tham, Li Jia Chen, Jason C Yam","doi":"10.1007/s11357-025-02066-x","DOIUrl":"10.1007/s11357-025-02066-x","url":null,"abstract":"<p><p>Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the aging population. Although frailty has been recognized as a potential risk factor, previous studies relying on static assessments cannot capture its dynamic nature. This study aims to prospectively evaluate the association between dynamic frailty trajectories and incident AMD. The baseline cohort included 462,573 UK Biobank participants who were free of AMD and had frailty phenotype (FP) data at enrollment. Among them, 53,059 with at least one follow-up FP assessment comprised the trajectory cohort. Participants were categorized as nonfrail, prefrail, or frail based on their FP scores. Annualized frailty progression (ΔFP/year) was estimated via linear regression. Cox models assessed hazard ratios (HRs) and 95% confidence intervals (CIs) for AMD. During a median follow-up of 11.8 years in the baseline cohort, 13,428 incident AMD cases (2.9%) were documented. Prefrail (HR:1.14; 95% CI:1.10-1.18) and frail (HR:1.36; 95% CI: 1.26-1.47) individuals had significantly higher AMD risks compared to nonfrail participants. In the frailty trajectory analysis with a median follow-up duration of 3.3 years, 852 incident AMD cases (1.6%) were recorded. Each 1-point FP increase conferred 28% higher AMD risk (HR: 1.28; 95% CI: 1.18-1.38), while each 0.1-point/year ΔFP increase independently elevated risk by 15% (HR: 1.15; 95% CI: 1.10-1.21). Compared to stable nonfrail, prefrailty aggravation showed highest AMD risk (HR: 2.26; 95% CI: 1.51-3.37), followed by frailty alleviation (HR: 1.73; 95% CI: 0.98-3.04) and frailty maintenance (HR: 1.72; 95% CI: 0.86-3.41). Progressive frailty trajectories, independent of baseline status, is associated with increased incident AMD risk. Early interventions targeting frailty progression may mitigate AMD risk in aging populations.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"7681-7691"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early-life exposures, biological age acceleration, and type 2 diabetes in adulthood: mediation analyses in the UK Biobank.","authors":"Denghui Hu, Diana van Heemst, Qiuyu Feng, Ko Willems van Dijk, Raymond Noordam","doi":"10.1007/s11357-026-02138-6","DOIUrl":"10.1007/s11357-026-02138-6","url":null,"abstract":"<p><p>Early-life exposures could affect the risk of type 2 diabetes (T2D) in adulthood, but the mechanisms remain unclear. We included 319,951 (54.5% women) UK Biobank participants free of T2D at baseline and within the first year of follow-up to investigate whether early-life exposures contribute to T2D through biological aging estimated using the Klemera-Doubal (KDM) and PhenoAge methods. We first examined associations of exposures with biological age and T2D, respectively, using multivariable-adjusted linear models and Cox regression models. Next, we investigated the role of biological age acceleration in exposure-T2D associations using mediation analyses. Overall, the mean (standard deviation) chronological age of participants was 56.3 (8.1) years, KDM age was 40.9 (13.1) years, and PhenoAge was 44.4 (10.0) years. 17,062 T2D cases developed during a median (interquartile range) follow-up of 14.3 (13.5-15.0) years. Maternal smoking around birth, being part of a multiple birth, earlier puberty, and being relatively plumper or thinner at age ten were associated with both a higher biological age and T2D risk, while having a higher birth weight and being breastfed were associated with a lower T2D risk. Biological age acceleration partly mediated the exposure-T2D associations, ranging from a proportion of 8.3% (95%CI: 6.0-13.1%) of the association between birthweight-T2D being mediated by PhenoAge to a proportion of 27.7% (95%CI: 15.3-48.5%) of the association between breastfeeding-T2D being mediated by KDM. In conclusion, early-life exposures were associated with biological age acceleration that partly mediated the exposure-T2D associations, highlighting the importance of addressing early-life risks and biological aging in prevention strategies.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"8385-8397"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA methylation signatures in skeletal muscle associated with physical function in healthy older adults.","authors":"Xiaoxiao Wen, Mingjing Chen, Guanhong Miao, Christopher Wu, Anna Picca, Javier A Tamargo, Xiangyang Lou, Kevin Wu, Stephen Anton, Christiaan Leeuwenburgh, Jinying Zhao","doi":"10.1007/s11357-026-02410-9","DOIUrl":"10.1007/s11357-026-02410-9","url":null,"abstract":"<p><p>Despite the substantial variability in physical function among older adults, the molecular mechanisms remain poorly characterized, particularly within skeletal muscle. This study aimed to determine the patterns of DNA methylation in skeletal muscle associated with physical function in healthy older adults. We analyzed DNA methylation (EPIC v2 array; 875,554 CpG sites) in skeletal muscle from 92 healthy older adults (median age 74; 62% female). Associations were examined across five phenotypes: Short Physical Performance Battery (SPPB), 6-min walk test (6MWT), handgrip strength, perceived disability (PAT-D), and lifestyle health (modified Life's Essential 8). Linear regression models adjusted for age, sex, race, BMI, and muscle fiber composition. Genomic inflation corrected via the BACON method (FDR < 0.05). Gene set enrichment analysis was performed on suggestive hits (FDR < 0.1). We identified significant differentially methylated probes (DMPs) and regions (DMRs) across all phenotypes: SPPB (70 DMPs, 22 DMRs), 6MWT (16 DMPs, 566 DMRs), handgrip strength (2 DMRs), PAT-D (19 DMPs, 1 DMR), and lifestyle health (2 DMPs). DMRs largely overlapped promoters. Identified genes overlapped known musculoskeletal and neurological GWAS hits, including RUNX2 and FOXL1 (bone mineral density), IGFBP3 (muscle mass), and NEK1 and SHANK1 (neurological function). Enrichment analysis revealed that 6MWT-associated genes relate to nervous and skeletal system development, while handgrip-associated genes involve cytoskeletal dynamics and protein assembly. Epigenetic variation in aging skeletal muscle is associated with physical function. The enrichment of pathways related to nervous and musculoskeletal development suggests specific epigenetic mechanisms underlying functional decline, offering potential targets for intervention in older adults.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"7597-7612"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148697356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel multi-omic biomarkers to combat oocyte and ovarian aging.","authors":"Pawel Kordowitzki, Shakchhi Joshi, Xutong Gong, Albert Kejun Ying, Jakub Wyroba, Joanna Kochan, Marcia C Haigis","doi":"10.1007/s11357-026-02119-9","DOIUrl":"10.1007/s11357-026-02119-9","url":null,"abstract":"<p><p>Understanding oocyte and ovarian aging has become critically important, as trends in family planning evolve, with many women choosing to have children later in life. The ovary, a crucial organ in female reproduction, is particularly susceptible to age-related changes and is one of the organs that exhibit functional deterioration most distinctly with age. The aging of female reproductive systems also affects longevity and various health outcomes. A better understanding of both oocyte and ovarian aging will lay the cornerstone to elucidate the phenomenon of longevity in women. Here, clinical data from 400 women of various ages undergoing intracytoplasmic sperm injection (ICSI) have been analyzed, including Anti-Müllerian Hormone (AMH) and Follicle-Stimulating Hormone (FSH) levels, the number of recovered oocytes, blastocyst rates, pregnancy rates, and live birth rates. Our analyses revealed significant differences in the aforementioned rates between patients of young and advanced age. For the biomarker analysis, we further utilised a novel predictive performance of age-associated gene expression signatures for oocyte aging, demonstrating its potential to provide molecular-level insights into oocyte quality over time. By analyzing RNA sequencing data generated from human oocytes of different ages, a genome-wide landscape of age-associated gene expression has been described. Additionally, metabolome profiling has been performed on young and reproductively aged mice, serving as a model for human ovaries. Changes in metabolites of the murine ovaries during aging have been recorded. In conjunction with traditional biomarkers, multiomics data represent a transformative approach in reproductive health, and they may offer personalised risk assessments and interventions to mitigate age-related fertility decline in women. Our metabolome profiling provides a valuable resource for elucidating the metabolomic basis of ovarian aging. Our findings offer novel insights into systemic shifts associated with oocyte and ovarian aging. This integrated approach may unlock new avenues for fertility preservation, ovarian rejuvenation, and assisted reproduction.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"8203-8228"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146112852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic brain functional connectivity in age-related hearing loss during auditory selective spatial attention.","authors":"Hongxing Liu, Yanru Bai, Mingkun Guo, Ran Zhao, Jianing Zhu, Guangjian Ni","doi":"10.1007/s11357-025-02069-8","DOIUrl":"10.1007/s11357-025-02069-8","url":null,"abstract":"<p><p>Age-related hearing loss (ARHL) is a common health problem that impairs auditory perception. However, the dynamic patterns of brain functional connectivity in ARHL during auditory spatial selective attention have not been thoroughly investigated. In this study, 32 older adults were recruited to investigate the dynamic brain functional connectivity in ARHL. First, an experimental paradigm for auditory spatial selective attention was designed, and neural electrical signals were recorded using electroencephalography. Then, a multilayer time-varying brain network was constructed based on multiple time windows, equally dividing each epoch signal to capture dynamic functional connectivity across time scales. Finally, the core layer brain network was identified by the multilayer time-varying brain network properties to investigate the changing patterns of network topology. Behavioral analysis revealed a significant negative correlation between the severity of hearing loss and auditory spatial selective attention performance. Multilayer time-varying brain network analysis revealed that worsening hearing loss was found to lead to increased inter-layer connectivity strength, decreased multilayer modularity and a higher participation coefficient. This suggests that the brain compensates by weakening the independence of local functional modules and enhancing cross-interaction. Core layer analysis further highlighted the critical role of the right parietal lobe in auditory spatial selective attention. It also suggested that connectivity between the right prefrontal and frontal lobes may play a compensatory role in ARHL. In conclusion, these findings provide important neuroscientific insights into the dynamic brain functional connectivity of ARHL, and potential biomarkers and time windows for the development of precision auditory rehabilitation strategies.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"7663-7680"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145855345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolvable soma theory of ageing: observations from the natural world.","authors":"Alessandro Fontana","doi":"10.1007/s11357-026-02115-z","DOIUrl":"10.1007/s11357-026-02115-z","url":null,"abstract":"<p><p>Ageing has traditionally been interpreted through declining selection gradients with age. The Evolvable Soma Theory of Ageing (ESTA) provides a complementary perspective by proposing that age-associated somatic changes reflect the late extension of the developmental program, which is shaped by evolution. These late-acting changes are epigenetic in nature, encoded in the genome, subject to germline-mediated modification, and may be viewed as developmentally regulated variants that have not yet been refined by selection. Here, we explore whether patterns observed in the natural world are consistent with key expectations derived from this framework. One such expectation is that species experiencing lower rates of evolutionary change may exhibit slower age-associated decline. In line with this idea, we examine long-lived species occupying ecological niches characterised by reduced competition and environmental turnover, as well as taxa often described as exhibiting high evolutionary stasis, and note that several display extended lifespans compared to related groups. Secondly, we examine evo-devo dynamics concerning the relationship between development and evolutionary history, and discuss their compatibility with the conceptual structure of ESTA. A third expectation is that stronger evolutionary pressure may influence life-history timing, including shifts in the age of sexual maturation; this possibility is explored through comparisons between bonobos and chimpanzees and through broader sex-specific patterns reported in mammals. Taken together, these observations do not constitute definitive tests but provide preliminary, qualitative support for the idea that evolutionary dynamics and ageing may be more closely intertwined than traditionally assumed, and they highlight directions for future investigation.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"8435-8447"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polluting cooking fuels and life satisfaction among middle-aged and older adults: a cross-sectional study from the Longitudinal Ageing Study in India.","authors":"Imnameren Longkumer, Soohyeon Ko, Priyanka deSouza, Rohit Bhatia, Rockli Kim, S V Subramanian","doi":"10.1007/s11357-026-02113-1","DOIUrl":"10.1007/s11357-026-02113-1","url":null,"abstract":"<p><p>Polluting cooking fuels are a major source of household air pollution and may reduce life satisfaction (LS). Yet, this relationship remains unexplored in India where polluting fuel use is still widespread. We utilized cross-sectional data from the Longitudinal Aging Study in India, a nationally representative study of individuals aged 45 years and above. Cooking fuel type was classified as households using clean fuels (CF) or non-CF. Based on kitchen type, non-CF was categorized into non-CF in separate kitchen, and non-CF without separate kitchen. We used multivariable regression to examine the association between polluting cooking fuels and LS and explored gender differences in this association. The analytical sample comprised 62,822 respondents (mean age 59.56 ± 10.52 years). The use of non-CF in separate and non-separate kitchen was 27.08% (n = 17,010) and 18.89% (n = 11,868), respectively. We observed that LS scores were highest among households using CF, followed by those using non-CF in separate kitchen, and lowest among households using non-CF without separate room for cooking. Additionally, in the fully adjusted model, a dose-response association with LS was observed corresponding to different levels of polluting cooking fuels (non-CF in separate kitchen: β = -0.51 [95% CI: -0.71, -0.31]; non-CF without separate kitchen: β = -1.42 [95% CI: -1.65, -1.19]). Multiple sensitivity analyses support the robustness of our findings. Gender was a significant effect modifier, with the interaction model revealing a stronger negative association between non-CF use and LS among women than among men. Our findings highlight the need for policies that promote an equitable clean fuel transition to enhance life satisfaction and well-being.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"8189-8202"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146112860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular exosome signature links hypertension and Alzheimer's disease.","authors":"Joakim A Bastrup, Jonas Folke, Sanne S Kaalund, Michel Rasmussen, Susana Aznar, Thomas Jepps","doi":"10.1007/s11357-026-02097-y","DOIUrl":"10.1007/s11357-026-02097-y","url":null,"abstract":"<p><p>Untreated hypertension is a risk factor for late-onset Alzheimer's disease (AD); however, this association is not well understood. The aim of this study was to reveal protein signatures that bridge the pathophysiological changes in hypertension to AD. Using untargeted proteomics, we analyzed brain samples from aged (30- and 40-week-old) spontaneously hypertensive rats (SHRs, n = 12), and age-matched normotensive Wistar Kyoto (WKY, n = 8) controls, and human AD patients (Braak stages 4-6) (n = 30), cerebral amyloid angiopathy (CAA) (n = 5), non-demented controls (Braak stages 0-3) (n = 37). Differential expression and pathway analyses in SHRs highlighted the 'extracellular exosome' pathway. This pathway also showed significant associations to differentially expressed proteins in AD and CAA patients. Comparison between species identified 24 proteins in SHRs and AD, whose trajectory pattern over the progression of hypertension, aligned with those observed during AD Braak stage progression, compared to respective controls. The proteins were similarly associated with extracellular exosomes. Immunostaining and spatial proteomics support vesicle accumulation and dysregulated exosome protein signatures in the cerebrovasculature of both SHR and AD brains. Additionally, the extracellular exosome pathway-association was not identified in a traditional model of familial AD (5xFAD). Our findings demonstrate cross-species translatability between AD and the SHR and provide novel mechanistic insights into a shared dysregulation of cerebral artery-associated exosomes.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"8265-8283"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146112914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}