GeroScience最新文献

{"title":"Treatment delay significantly increases mortality in colorectal cancer: a meta-analysis","authors":"Zoltan Ungvari, Mónika Fekete, János Tibor Fekete, Andrea Lehoczki, Annamaria Buda, Gyöngyi Munkácsy, Péter Varga, Anna Ungvari, Balázs Győrffy","doi":"10.1007/s11357-025-01648-z","DOIUrl":"https://doi.org/10.1007/s11357-025-01648-z","url":null,"abstract":"<p>Delaying the initiation of cancer treatment increases the risk of mortality, particularly in colorectal cancer (CRC), which is among the most common and deadliest malignancies. This study aims to explore the impact of treatment delays on mortality in CRC. A systematic literature search was conducted in PubMed, Web of Science, and Scopus for studies published between 2000 and 2025. Meta-analyses were performed using random-effects models with inverse variance method to calculate hazard ratios (HRs) for both overall and cancer-specific survival at 4-, 8-, and 12-week treatment delay intervals, with heterogeneity assessed through <i>I</i>²-statistics and publication bias evaluated using funnel plots and Egger’s test. A total of 20 relevant studies were included in the meta-analysis. The analyses of all patients demonstrated a progressively increasing risk of 12–39% with longer treatment delays (4 weeks, HR = 1.12; 95% CI, 1.08–1.16; 8 weeks, HR = 1.24; 95% CI, 1.16–1.34; 12 weeks, HR = 1.39; 95% CI, 1.25–1.55). In particular, incrementally higher hazard ratios were observed for all–cause mortality at 4 weeks (HR = 1.14; 95% CI, 1.09–1.18), 8 weeks (HR = 1.29; 95% CI, 1.20–1.39), and 12 weeks (HR = 1.47; 95% CI, 1.31–1.64). In contrast, cancer-specific survival analysis showed a similar trend but did not reach statistical significance (4 weeks, HR = 1.07; 95% CI, 0.98–1.18; 8 weeks, HR = 1.15; 95% CI, 0.95–1.39; 12 weeks, HR = 1.23; 95% CI, 0.93–1.63). Treatment delays in colorectal cancer patients were associated with progressively worsening overall survival, with each 4-week delay increment leading to a substantially higher mortality risk. This study suggests that timely treatment initiation should be prioritized in clinical practice, as these efforts can lead to substantial improvements in survival rates.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"138 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797924","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}

{"title":"Bilingualism and “brain reserve” in subregions of the hippocampal formation","authors":"Katharina Peitz, Nora Bittner, Stefan Heim, Svenja Caspers","doi":"10.1007/s11357-025-01639-0","DOIUrl":"https://doi.org/10.1007/s11357-025-01639-0","url":null,"abstract":"<p>With aging, the hippocampal formation shows variable structural atrophy, which is associated with a decline in cognitive performance. Bilingualism is related to higher hippocampal gray matter volume (GMV), potentially representing a form of brain reserve in aging. However, the differential influence of bilingualism on hippocampal subregions remains unclear. Thus, we investigated GMV differences and differences in age-GMV relationships between mono- and bilinguals in the hippocampal formation and its subregions, hippocampus proper and subicular complex. We included 661 adults aged 19 to 85 years (257 monolinguals, 404 sequential bilinguals, predominantly native German speakers with variable second language background) from the population-based 1000BRAINS cohort. GMV differences in mono- vs. bilinguals were assessed for six regions of interest (hippocampal formation, hippocampus proper, and subicular complex; each left and right) using analyses of covariance. Effects of bilingualism on age-GMV relationships were investigated via moderation analyses. We found higher GMV in bilinguals in the bilateral subicular complex, while only a trend towards this effect existed for the hippocampal formation. Moderation analyses revealed similar age-GMV relationships between mono- and bilinguals for all regions of interest. Higher GMV in bilinguals’ hippocampal formation seems specifically attributable to the subicular complex rather than the hippocampus proper. With similar age-GMV relationships for mono- and bilinguals, bilingual brain reserve in the subicular complex may persist over time. This may be particularly beneficial since subicular atrophy has previously been associated with higher risk for dementia. Altogether, a differential impact of bilingualism on hippocampal subregions has been demonstrated. </p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"95 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805860","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}

{"title":"The selection of participants for interventional microbiota trials involving cognitively impaired older adults","authors":"Adam Golden, Cynthia Williams, Hariom Yadav, Michal M. Masternak, Corinne Labyak, Peter J. Holland, Andrea Y. Arikawa, Shalini Jain","doi":"10.1007/s11357-025-01641-6","DOIUrl":"https://doi.org/10.1007/s11357-025-01641-6","url":null,"abstract":"<p>Gut microbiota plays a significant role in nutrient extraction, metabolism, and immune function. Thus, the growing number of microbiome studies seek to link the presence and prevalence of specific bacteria, fungi, and viruses with a variety of physiological and disease outcomes. However, recruiting a diverse group of patients has been a challenge. Poor hearing and vision, lack of transportation, cognitive impairment, and a non-English primary language may interfere with patient enrollment as well as adherence to the requirements of a Microbiome study. Much of what we do know about diseases in older adults comes from studies that exclude many of these patients commonly encountered in clinical practice. The purpose of this review article is to highlight recruitment and retention strategies for engaging people who typically do not participate in microbiome studies, and it seeks to develop and explicate inclusion and exclusion criteria to promote more robust study results.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"1 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782534","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}

{"title":"Comparative effects of angiotensin II stimulating and inhibiting antihypertensives on dementia risk: a systematic review and meta-analysis","authors":"Eyayaw Ashete Belachew, Gregory M. Peterson, Woldesellassie M. Bezabhe","doi":"10.1007/s11357-025-01600-1","DOIUrl":"https://doi.org/10.1007/s11357-025-01600-1","url":null,"abstract":"<p>Studies comparing the effects of Angiotensin II (Ang-II) stimulating and inhibiting antihypertensive medications (AHMs) on dementia risk have reported inconsistent findings. Based on the PRISMA guidelines, this study was performed to pool these findings. We searched PubMed, Scopus, Embase Ovid, PsycINFO, and CINAHL from inception to 22 May 2024 for randomised controlled trials (RCTs) and observational studies that compared the use of Ang-II stimulating (thiazides, Ang-II receptor blockers, and dihydropyridine calcium channel blockers) and inhibiting AHMs (β-blockers, angiotensin-converting enzyme inhibitors, and non-dihydropyridine calcium channel blockers) and the subsequent risk of developing dementia. Two reviewers independently performed study selection, data extraction, and quality assessment. Random effects meta-analysis models were used to calculate hazard ratios (HRs) or risk ratios (RRs) with their confidence intervals (CIs). All-cause dementia was the primary outcome. Alzheimer’s disease (AD), vascular dementia (VD), and mild cognitive impairment (MCI) were secondary outcomes. We included 18 studies with 1,883,283 participants. Observational studies showed that the use of Ang-II stimulating AHMs reduced the risk of all-cause dementia by 13% (HR = 0.87; 95% CI = 0.82–0.93) compared with Ang-II inhibiting AHMs. The risk of AD was reduced by 12% (HR = 0.88; 95% CI = 0.86–0.90), VD by 19% (HR = 0.81; 95% CI = 0.72–0.91), and MCI by 24% (HR = 0.76; 95% CI = 0.68–0.85) in these studies. A meta-analysis of four RCTs revealed a non-significant 8% reduction in dementia risk with Ang-II stimulating AHMs versus control (RR = 0.92; 95% CI = 0.79–1.08). Observational evidence suggests that Ang-II stimulating AHMs may offer neuroprotective benefits relative to Ang-II inhibiting AHMs.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"18 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143775641","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}

{"title":"NIA Caenorhabditis Intervention Testing Program: identification of robust and reproducible pharmacological interventions that promote longevity across experimentally accessible, genetically diverse populations","authors":"Monica Driscoll, Christine A. Sedore, Brian Onken, Anna L. Coleman-Hulbert, Erik Johnson, Patrick C. Phillips, Gordon Lithgow","doi":"10.1007/s11357-025-01627-4","DOIUrl":"https://doi.org/10.1007/s11357-025-01627-4","url":null,"abstract":"<p>A core facet of the National Institute on Aging’s mission is to identify pharmacological interventions that can promote human healthy aging and long life. As part of the comprehensive effort toward that goal, the NIA Division of Biology of Aging established the <i>Caenorhabditis</i> Intervention Testing Program (CITP) in 2013. The <i>C. elegans</i> model (with an ~ 21 day lifespan) has led the field in dissection of longevity genetics and offers features that allow for relatively rapid testing and for the potential elaboration of biological mechanisms engaged by candidate geroprotectants. CITP builds on this foundation by utilizing a genetically diverse set of intervention test strains so that “subjects” represent genetic diversity akin to that that between mouse and humans. Another distinctive aspect of the CITP is a dedicated focus on reproducibility of longevity outcomes as labs at three independent test sites confirm positive outcomes. The overall goal of the <i>Caenorhabditis</i> Intervention Testing Program (CITP) is to identify robust and reproducible pro-longevity interventions affecting genetically diverse cohorts in the <i>Caenorhabditis</i> genus. A strong Data Collection Center supports data collection and dissemination. Pharmacological interventions tested by CITP can be nominated by the general public, directed by in-house screens, or supported by published scientific literature. As of December 2024, CITP tested &gt; 75 compounds and conducted &gt; 725,000 animal assays over 891 trials. We identified 12 compounds that confer a ≥ 20% increase in median lifespan to reproducibly and robustly extend lifespan across multiple strains and labs. Five of these interventions have pro-longevity impact reported in the mouse literature (most CITP positive interventions are not tested yet in mouse). As part of the celebration of the 50th Anniversary of the NIA, we review the development history and accomplishments of the CITP program, and we comment on translation and the promise of advancing understanding of fundamental aging biology that includes the pharmacological intervention/health interface.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"3 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143767082","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}

{"title":"Aging, mitochondrial dysfunction, and cerebral microhemorrhages: a preclinical evaluation of SS-31 (elamipretide) and development of a high-throughput machine learning-driven imaging pipeline for cerebromicrovascular protection therapeutic screening","authors":"Roland Patai, Krish Patel, Boglarka Csik, Rafal Gulej, Raghavendra Y. Nagaraja, Dorina Nagy, Siva Sai Chandragiri, Santny Shanmugarama, Kiana Vali Kordestan, Mark Nagykaldi, Shoba Ekambaram, Anna Ungvari, Andriy Yabluchanskiy, Stefano Tarantini, Zoltan Benyo, Anna Csiszar, Zoltan Ungvari, Adam Nyul-Toth","doi":"10.1007/s11357-025-01634-5","DOIUrl":"https://doi.org/10.1007/s11357-025-01634-5","url":null,"abstract":"<p>Cerebral microhemorrhages (CMHs, also known as cerebral microbleeds) contribute to vascular cognitive impairment and dementia (VCID), with aging and hypertension being key risk factors. Mitochondrial oxidative stress is a hallmark of cerebrovascular aging, leading to endothelial dysfunction. This study tests the hypothesis that increased mitochondrial oxidative stress contributes to age-related CMH susceptibility and evaluates the mitochondrial-targeted antioxidative peptide SS-31 (elamipretide) as a potential protective agent in an aged, hypertensive mouse model. Concurrently, we developed a high-throughput, machine learning–driven imaging pipeline to enhance CMH quantification and facilitate the screening of anti-aging vasoprotective interventions. To detect CMHs, brain sections were labeled with diaminobenzidine (DAB) and digitized using a slide scanner-based imaging platform. We developed multiple quantification tools, including color space transformation for enhanced contrast separation and a supervised machine-learning approach utilizing a random forest algorithm to generate whole-brain 3D reconstructions and precisely localize CMHs. We optimized a semi-automated detection method integrating color space transformation and machine learning, benchmarking it against traditional manual counting and color deconvolution-based approaches. While SS-31 treatment did not significantly mitigate hypertension-induced CMH burden in aged mice, our high-throughput imaging pipeline provided a reliable, scalable, and unbiased approach to CMH detection, reducing processing time while improving accuracy. This methodological advancement paves the way for future preclinical studies evaluating therapeutic strategies for cerebrovascular protection in aging. Our findings underscore the need for multi-targeted interventions to mitigate CMH-related neurovascular impairments and prevent VCID.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"32 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143758088","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}

{"title":"Preoperative physical resilience indicators and their associations with postoperative outcomes","authors":"Marjolein Klop, René J. F. Melis, G. M. E. E. Geeske Peeters, Guillaume S. C. Geuzebroek, Robin H. Heijmen, Richard J. A. van Wezel, Jurgen A. H. R. Claassen","doi":"10.1007/s11357-025-01633-6","DOIUrl":"https://doi.org/10.1007/s11357-025-01633-6","url":null,"abstract":"<p>The health benefit of surgery in older adults may be outweighed by negative effects on cognitive or physical function. Physical resilience is defined as the potential for recovery after a stressor such as surgery. We assessed associations between physical resilience measured by orthostatic blood pressure (BP) and cerebral oxygenation recovery or grip work (sustained hand grip strength; GW) and postoperative outcome in two cohorts of (older) surgical patients. The first cohort (CTC) consisted of patients undergoing complex cardiothoracic surgery. The second cohort (GRR) held geriatric outpatients undergoing various surgical procedures. Outcome measures were length of stay (LoS) and postoperative complications. Negative binomial (LoS) and ordinal (complications) regression models were used to determine associations. 261 patients (113 CTC and 148 GRR) underwent surgery. Median LoS was 10 (CTC) and 5 days (GRR). Postoperative complications occurred in 80% (CTC) and 45% (GRR) of patients. In CTC, 10 mmHg higher systolic BP recovery was associated with a 12% shorter LoS (incidence rate ratio (IRR) 0.88 (95% CI 0.78–0.98)). 10 s longer sustained hand grip was associated with a 5% shorter LoS in GRR (IRR 0.95 (0.90–1.00)), but a 7% longer LoS in CTC (IRR 1.07 (1.03–1.11)). No significant associations were found with postoperative complications. Orthostatic cerebral oxygenation recovery in CTC was not significantly associated with any postoperative outcome. Our results imply that resilience indicators might be associated with LoS after surgery. Future research should seek to replicate our findings and investigate whether adding resilience parameters to preoperative assessment can support postoperative outcome prediction.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"107 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143767083","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}

{"title":"Apathy, gait slowness, and executive dysfunction (AGED) triad: opportunities to predict and delay dementia onset.","authors":"Frederico Pieruccini-Faria, Vladimir Hachinski, Surim Son, Manuel Montero-Odasso","doi":"10.1007/s11357-024-01372-0","DOIUrl":"10.1007/s11357-024-01372-0","url":null,"abstract":"<p><p>This study investigates whether older adults diagnosed with the apathy, gait impairment, and executive dysfunction (AGED) triad, frequently associated with cerebrovascular disease and confounded with depression, have earlier dementia onset. We followed 322 community-dwelling older individuals (mean age 72.0 ± 6.4 years; 58.3% women) free of dementia at baseline for up to 9 years. The AGED triad was identified when gait slowness (< 1 m/s), apathy (assessed by Geriatric Depression Scale-3A with ≥ 2 items), and executive dysfunction (assessed by the 75th percentile of Trail Making Test-part B by age range) were simultaneously present. Incident dementia was diagnosed using the clinical dementia rating scale. Over the 9-year follow-up (mean 45.1 ± 28.6 months), 44 participants (13.6%) converted to dementia. Sixteen participants (5.0%) were diagnosed with AGED triad + and showed a significantly higher risk of earlier conversion to dementia compared with AGED triad- (hazard ratio = 5.08, 95%CI 2.16-11.97; p = 0.0001), as well as to those with only one AGED factor or fewer AGED factors. Hypertension and diabetes were 2 and 3 times more prevalent, respectively, in individuals with AGED triad + . These findings suggest that the AGED triad serves as a simplified and effective behavioral marker for accelerated progression to dementia.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"1859-1871"},"PeriodicalIF":5.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389824","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}

{"title":"Sarcopenia and the management of spinal disease in the elderly.","authors":"Alexander R Evans, Lonnie Smith, Joshua Bakhsheshian, David B Anderson, James M Elliott, Hakeem J Shakir, Zachary A Smith","doi":"10.1007/s11357-024-01300-2","DOIUrl":"10.1007/s11357-024-01300-2","url":null,"abstract":"<p><p>Sarcopenia, generally defined by the loss of skeletal mass and function, may disproportionately affect elderly individuals and heavily influence spinal disease. Muscle atrophy is associated with myriad clinical problems, including thoracic kyphosis, increased sagittal vertical axis (SVA), spinal implant failures, and postoperative complications. As such, the aim of this narrative review is to synthesize pertinent literature detailing the intersection between sarcopenia and the impact of sarcopenia on the management of spine disease. Specifically, we focus on the domains of etiology, diagnosis and assessment, impact on the cervical and lumbar spine, spinal augmentation procedures, neoplastic disease, whiplash injury, and recovery/prevention. A narrative review was conducted by searching the PubMed and Google Scholar databases from inception to July 12, 2024, for any cohort studies, systematic reviews, or randomized controlled trials. Case studies and conference abstracts were excluded. Diagnosis of sarcopenia relies on the assessment of muscle strength and quantity/quality. Strength may be assessed using clinical tools such as gait speed, timed up and go (TUG) test, or hand grip strength, whereas muscle quantity/quality may be assessed via computed tomography (CT scan), magnetic resonance imaging (MRI), and dual-energy X-ray absorptiometry (DXA scan). Sarcopenia has a generally negative impact on the clinical course of those undergoing cervical and lumbar surgery, and may be predictive of mortality in those with neoplastic spinal disease. In addition, severe acceleration-deceleration (whiplash) injuries may result in cervical extensor muscle atrophy. Intervention and recovery measures include nutrition or exercise therapy, although the evidence for nutritional intervention is lacking. Sarcopenia is a widely prevalent pathology in the advanced-age population, in which the diagnostic criteria, impact on spinal pathology, and recovery/prevention measures remain understudied. However, further understanding of this therapeutically challenging pathology is paramount, as surgical outcome may be heavily influenced by sarcopenia status.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"1471-1484"},"PeriodicalIF":5.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975529","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}

{"title":"Impaired brain ability of older adults to transit and persist to latent states with well-organized structures at wakeful rest.","authors":"Zijin Liu, Haishuo Xia, Antao Chen","doi":"10.1007/s11357-024-01366-y","DOIUrl":"10.1007/s11357-024-01366-y","url":null,"abstract":"<p><p>The intrinsic brain functional network organization continuously changes with aging. By integrating spatial and temporal information, the process of how brain networks temporally reconfigure and remain well-organized spatial structure largely reflects the brain function, thereby holds the potential to capture its age-related declines. In this study, we examined the spatiotemporal brain dynamics from resting-state functional Magnetic Resonance Imaging (fMRI) data of healthy young and older adults using a Hidden Markov Model (HMM). Six brain states were generated by HMM, with the young group showing higher fractional occupancy and mean dwell time in states 1, 3, and 4 (SY1, SY2 and SY3), and the older group in states 2, 5, and 6 (SO1, SO2 and SO3). Importantly, comparisons of transition probabilities revealed that the older group showed a reduced brain ability to transition into states dominated by the younger group, as well as a diminished capacity to persist in them. Moreover, graph analysis revealed that these young-specific states exhibited higher modularity and k-coreness. Collectively, these findings suggested that the older group showed impaired brain ability of both transition into and sustain well spatially organized states. This emphasized that the temporal changes in brain state organization, rather than its static mode, could be a key biomarker for detecting age-related functional decline. These insights may pave the way for targeted interventions aimed at mitigating cognitive decline in the aging population.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"1761-1776"},"PeriodicalIF":5.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365044","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}