GeroScience最新文献

{"title":"HealthAge: evaluation of intrinsic capacity changes in humans, mice, and killifish to explore the biology of aging.","authors":"Sophie Guyonnet,Claudie Hooper,Heike A Bischoff-Ferrari,Angelo Parini,Yohan Santin,Jean-Philippe Pradère,Cédric Dray,Bruno Vellas,","doi":"10.1007/s11357-025-01718-2","DOIUrl":"https://doi.org/10.1007/s11357-025-01718-2","url":null,"abstract":"HealthAge was devised by a conglomerate of research groups in Toulouse, France, with the combined goal of narrowing the lifespan-healthspan gap through novel translational bench-to-bedside research studies. HealthAge comprises the \"INStitute for Prevention\" \"healthy aging\" and \"medicine Rejuvenative\" (INSPIRE) human translational, outbred SWISS mice and African turquoise killifish (GRZ strain) cohorts in which aging is studied based on the concept of intrinsic capacity (IC). In this narrative review, we describe the three INSPIRE aging models (human cohort, n = 1109, age range 20 -102 years old with mean age ± standard deviation, 62.4 ± 19.0 years and 61.9% female; outbred SWISS mice, n = 1576 and African Turquoise killifish, n = 300) and explain how IC is assessed at the clinical (in humans) and biological level over time. HealthAge strives to elucidate the underlying biology of IC and to identify biomarkers of IC declines and novel gero-therapeutics using the clinical and biological data and biospecimens collected prospectively in the three species. The data sharing policy will foster scientific discovery through new multi-disciplinary collaborations. Thus, HealthAge will promote healthy aging using a unique translational platform based on IC phenotyping with the ultimate goal of preventing loss of human independence and alleviating health costs associated with an aging population.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"13 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295703","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":"Age-independent anti-angiogenic therapy for choroidal neovascularization by targeting secretogranin III.","authors":"Chengchi Huang,Hong Tian,Wei Li","doi":"10.1007/s11357-025-01732-4","DOIUrl":"https://doi.org/10.1007/s11357-025-01732-4","url":null,"abstract":"Recent studies reported that anti-angiogenic drugs targeting vascular endothelial growth factor (VEGF) alleviate choroidal neovascularization (CNV) in young but not aged animals. We recently developed a disease-targeted anti-angiogenic therapy against secretogranin III (Scg3), which selectively binds to diseased but not healthy vessels in young mice. Herein, using a unique in vivo ligand binding assay, we predicted and confirmed that Scg3 selectively binds CNV vessels in both young and aged mice. In contrast, VEGF with minimal increased binding to CNV vessels exhibited an age-dependent decline in binding to both CNV and healthy vessels with negligible binding in aged mice. Based on these binding activity patterns, we further predicted and confirmed that a humanized anti-Scg3 antibody effectively alleviated laser-induced CNV in both young and aged mice, whereas the anti-VEGF drug aflibercept was effective only in young mice. These findings suggest that enhanced binding of Scg3 to CNV vessels in both age groups provides a molecular basis for an age-independent anti-Scg3 therapy, offering potential to address anti-VEGF resistance in clinical treatment of wet age-related macular degeneration with CNV.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"23 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295706","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":"Linking sleep microstructure, blood markers of inflammation and metabolism, and cognition: mediation analysis in the osteoporotic fractures in men study.","authors":"Claire Suen, Julia Ma, Xihong Lin, Robert J Thomas, M Brandon Westover, Katie Stone, Kristine Yaffe, Kristine E Ensrud, Susan Redline, Rudolph E Tanzi, Haoqi Sun, Can Zhang","doi":"10.1007/s11357-025-01730-6","DOIUrl":"https://doi.org/10.1007/s11357-025-01730-6","url":null,"abstract":"<p><p>The sleep electroencephalographic (EEG) microstructure is explicitly related to brain functions, such as sleep spindle and memory consolidation. On the other hand, given the crosstalk between the central nervous system and the body, including inflammation regulation and metabolic systems, there is a gap in understanding the bidirectional relationship between sleep and these systems that contribute to cognitive health. We used data from the Osteoporotic Fractures in Men (MrOS) Study, a six-site cohort study of community-dwelling men 65 years or older. We analyzed 1898 participants who participated in the Sleep Visit and Visit 2. We analyzed 41 sleep EEG microstructures and 9 blood markers. The outcome was the Modified Mini-Mental State Examination (3MS) in Visit 2. We used partial Spearman's correlation to investigate the pairwise associations and performed 3MS prediction. We then performed mediation analyses using each blood marker as the exposure and each sleep EEG microstructure as the mediator, and then the other way around. Sleep EEG microstructures were more strongly correlated with 3MS than blood markers in general. The best Pearson's correlation between the actual and predicted 3MS scores was 0.45 (95% confidence interval 0.38-0.47) using sleep EEG microstructures and covariates, which provided little improvement compared to using covariates alone (0.43, 0.39-0.48). Leptin and 3MS score were associated (Spearman's ρ = 0.053, p = 0.02) while adjusting for covariates. The association between leptin and 3MS score was mediated by fast spindle density (indirect effect = 0.030, p = 0.02) and spindle-slow oscillation (SO) overlap (indirect effect = 0.029, p = 0.02). No blood marker mediated the association between sleep EEG microstructure and 3MS. Instead, the following sleep EEG microstructures had significant direct associations with 3MS independent of the blood markers: theta power during N1 and REM (direct effect = - 0.57 and - 0.46, p = 0.0002 and 0.007, respectively), spindle density (direct effect = 0.39, p = 0.006), and spindle-SO coupling overlap (direct effect = 0.29, p = 0.01). The blood markers of inflammation and metabolism were less predictive of and indirectly associated with global cognition compared to the sleep EEG microstructures. Future work is needed to confirm these results in an experimental setting.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293631","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":"Synaptic pruning genes networks in Alzheimer's disease: correlations with neuropathology and cognitive decline.","authors":"Cristina Sanfilippo, Paola Castrogiovanni, Rosa Imbesi, Paolo Fagone, Grazia Scuderi, Manlio Vinciguerra, Michelino Di Rosa","doi":"10.1007/s11357-025-01740-4","DOIUrl":"https://doi.org/10.1007/s11357-025-01740-4","url":null,"abstract":"<p><p>Synaptic pruning (SP) is a critical process in brain development and maintenance, essential for refining neural circuits by eliminating weak or redundant synapses. Dysregulation of SP has been implicated in neurodegenerative disorders such as Alzheimer's disease (AD). Studying the regulation of SP genes across the lifespan and their variation by sex and age is crucial to understanding the interplay between aging, sex, and AD pathogenesis. This study comprehensively analyzes the expression of SP-related genes, including complement system components (C1QA, C1QB, C1QC, C1S, C1R, C3), microglial regulators (ITGB2, ITGAM), and astrocytic factors (MERTK, MEGF10), as well as synaptic protective signals (CD47, SIRPA) in 2294 non-demented healthy controls (NDHC) and 1555 AD patients, stratified by sex, age, and brain area. Our findings reveal significant upregulation of most SP-related genes in AD brains, except for CD47 and SIRPA. Sex-specific patterns emerged, with males exhibiting stronger associations between complement genes and AD pathology, compared to females. Notably, in NDHC, females displayed higher baseline expression of SP-related genes (except CD47), but these sex differences diminished in AD, indicating disease-driven convergence. Age-related dynamics further highlighted distinct profiles, with males showing progressive upregulation of SP genes in NDHC, whereas females exhibited early senescence-like suppression followed by late-life compensatory changes. In AD, males demonstrated early complement dysregulation, while females displayed a pronounced inflammatory shift in advanced age. Region-specific analyses revealed heterogeneity, with the diencephalon showing the highest gene expression in NDHC males, while AD flattened regional differences in males but amplified variability in females. Correlation analyses linked complement and microglial genes to amyloid and tau pathology, with sex-specific associations. Principal component analysis (PCA) and Gene Ontology (GO) highlighted disrupted coordination between microglia, astrocytes, and neurons in AD. Protein expression analysis using the Human Protein Atlas revealed sex-specific differences in the localization of complement and microglial proteins in the prefrontal cortex. These findings underscore the complex interplay of sex, age, and regional factors in SP regulation, implicating complement overactivation, microglial dysfunction, and astrocytic phagocytosis in AD pathogenesis.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293632","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":"Impact of lifestyle factors on quantitative motor and cognitive performance: insights from a longitudinal study on healthy ageing.","authors":"Milan Zimmermann, Ulrike Sünkel, Isabel Wurster, Stefanie Lerche, Markus A Hobert, Claudia Schulte, Anna-Katharina von Thaler, Daniela Berg, Walter Maetzler, Andreas Fallgatter, Gerhard W Eschweiler, Thomas Gasser, Kathrin Brockmann, Benjamin Roeben","doi":"10.1007/s11357-025-01731-5","DOIUrl":"https://doi.org/10.1007/s11357-025-01731-5","url":null,"abstract":"<p><p>The process of ageing is extremely variable in progression and phenotypic features including significant variations in disease milestones, such as cognitive impairment, frailty, or recurrent falls. Our aim was to analyze the influence of lifestyle factors on motor and cognitive performance in a longitudinal ageing study in older people on healthy ageing. We conducted a longitudinal analysis in a cohort of 744 older participants (mean 70 years) over an 8-year period. Cognitive performance was assessed using the Consortium to Establish a Registry for Alzheimer's Disease (CERADplus) test battery, including the Trail Making Test (TMT) for executive function. Gait performance was evaluated by measuring gait velocity. Dual-task performance was assessed by measuring gait velocity while checking boxes. Body Mass Index (BMI) was also recorded. Symptoms of depression were examined using Beck's Depression Inventory (BDI-II). We observed higher cognitive functions in individuals adhering to a high-frequency physical activity regimen and a resilient plant-based diet. Additionally, these individuals exhibited lower BDI-II scores and experienced mitigated cognitive decline. Participants who combined high physical activity, a high intake of plant-based foods, and extensive education-referred to as having a high \"successful ageing index\" -maintained nearly constant CERADplus total scores over the 8-year period. Protective lifestyle factors are linked to better cognitive and motor performance and a slower decline in cognitive function, indicating healthy ageing. Since the factors diet and exercise are modifiable, adopting them may enhance cognitive performance and autonomy in older adults.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274715","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":"Impact of sarcopenia and obesity on skeletal muscle size, gene expression, and mitochondrial function.","authors":"Hector G Paez, Christopher R Pitzer, Jessica L Halle, Peter J Ferrandi, James A Carson, Junaith S Mohamed, Stephen E Alway","doi":"10.1007/s11357-025-01726-2","DOIUrl":"https://doi.org/10.1007/s11357-025-01726-2","url":null,"abstract":"<p><p>Skeletal muscle is a primary tissue of dysfunction during both aging and obesity. Recently, the coincidence of obesity and aging has gained attention due to the intersection of the obesity epidemic with an aging demographic. Both aging and obesity are associated with marked defects in skeletal muscle metabolic health. Despite these findings, we have a poor understanding of how obesity and aging may interact to impact skeletal muscle mass and metabolic health. Therefore, we investigated the impact of high-fat diet (HFD)-induced obesity on skeletal muscle mass, mitochondrial function, transcriptomics, and whole-body metabolism in young and aged mice. We observed main effects of diet and age on several measures of whole-body metabolic function (VO₂, VCO₂, and RER). Complex I-driven mitochondrial proton leak was significantly elevated by HFD-induced obesity across both age groups; however, a main effect of aging for reduced complex I leak was detected in the soleus muscle. Interestingly, aged animals fed a HFD did not exhibit lower muscle mass than chow-fed young animals, but did present with stark increases in muscle triglyceride content and a unique transcriptional response to HFD. HFD-induced obesity impacted the muscle transcriptome differently in the muscles of young and aged mice, indicating that obesity can change altered gene expression with age. Our findings suggest that the presence of obesity can both compound and counteract age-associated changes to muscle mass, gene expression, and mitochondrial function.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274716","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":"Epigenetic aging mediates the association between life course socioeconomic status and decrements in kidney function across a decade.","authors":"Agus Surachman, Meera N Harhay, Rose Ann DiMaria-Ghalili, Anthony S Zannas, David M Almeida, Christopher L Coe","doi":"10.1007/s11357-025-01728-0","DOIUrl":"10.1007/s11357-025-01728-0","url":null,"abstract":"<p><p>Epigenetic aging measures are novel molecular indicators of biological aging that predict age-related chronic disease. We examined whether several established indices of epigenetic aging mediated the association between life course socioeconomic status (SES) and decrements in kidney function across a decade. Biomarker data were from 252 non-Hispanic (NH) Black and white participants who had consented to genetic analyses in Wave 2 (2004-2009) and 3 (2014-2021) of the Midlife in the United States study (MIDUS). Life course SES included parental education, a proxy of early life SES, and a composite score of adult SES based on the highest education level, household income to poverty line ratio, health insurance coverage, perception of the availability of money to meet needs, and difficulty level paying monthly bills. We included five measures of epigenetic age accelerations (EAA), based on the residuals after each epigenetic clock was regressed on chronological age (Horvath, Horvath blood and skin, Hannum, PhenoAge, and GrimAge) and one measure of the pace of aging (DunedinPACE) obtained during MIDUS 2. Kidney function was based on serum creatinine-based estimated glomerular filtration rate (eGFR), calculated using the CKD-EPI formula (without race adjustment). We calculated absolute decrements in eGFR across 11 years between MIDUS waves 2 and 3. Analyses were adjusted for age, sex, and health-related covariates (currently smoking, obese, hypertension, and insulin resistance). Lower adult SES and accelerated epigenetic aging, especially accelerated GrimAge and faster DunedinPACE pace of aging, mediated the association between lower parental education and larger decrements in eGFR. Accelerated epigenetic aging is associated with larger decrements in kidney function across a decade and may be one of the critical explanatory pathways for the higher burden of chronic kidney disease (CKD) among lower SES individuals.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274714","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 compensatory effect of education as revealed by resting-state electroencephalographic alpha rhythms in patients with dementia due to Parkinson's disease: findings from an exploratory study.","authors":"Susanna Lopez, Claudio Del Percio, Roberta Lizio, Giuseppe Noce, Dharmendra Jakhar, Andrea Soricelli, Marco Salvatore, Bahar Güntekin, Görsev Yener, Federico Massa, Dario Arnaldi, Francesco Famà, Matteo Pardini, Raffaele Ferri, Filippo Carducci, Bartolo Lanuzza, Fabrizio Stocchi, Laura Vacca, Chiara Coletti, Moira Marizzoni, John-Paul Taylor, Lutfu Hanoğlu, Nesrin Helvacı Yılmaz, İlayda Kıyı, Yağmur Özbek-İşbitiren, Anita D'Anselmo, Laura Bonanni, Roberta Biundo, Fabrizia D'Antonio, Giuseppe Bruno, Angelo Antonini, Franco Giubilei, Sofia Cuoco, Paolo Barone, Giovanni B Frisoni, Rossella Rotondo, Francesca De Pandis, Claudio Babiloni","doi":"10.1007/s11357-025-01703-9","DOIUrl":"https://doi.org/10.1007/s11357-025-01703-9","url":null,"abstract":"<p><p>Here, we investigated whether educational attainment influences the neurophysiological mechanisms underlying vigilance regulation, as reflected in resting-state eyes-closed electroencephalographic (rsEEG) rhythms, in patients with dementia due to Parkinson's (PDD) and Lewy body disease (DLB). Clinical, demographic, and rsEEG data were obtained from an international database, including PDD patients (N = 75), DLB patients (N = 50), and cognitively unimpaired older controls (Healthy; N = 54). Each group was partitioned into low (Edu-) and high (Edu+) educational attainment subgroups, matched for age, sex, and cognitive-motor status. We analyzed rsEEG rhythms across the individual delta, theta, and alpha frequency bands. Cortical rsEEG source topography was estimated using eLORETA freeware. In the Healthy group, Edu+ participants exhibited significantly greater widespread rsEEG alpha source activities compared to Edu- participants, possibly reflecting neuroprotective neurophysiological mechanisms. Conversely, in the PDD group, Edu+ patients showed lower widespread rsEEG alpha source activities than Edu- patients, possibly indicating compensatory mechanisms. No significant differences in rsEEG source activities were observed between DLB-Edu+ and DLB-Edu- patients. Educational attainment may be associated with compensatory mechanisms that counteract the abnormal neurophysiological processes underlying rsEEG alpha rhythms and vigilance regulation in PDD patients, but not in DLB patients. Future studies combining rsEEG and neuroimaging techniques should investigate the metabolic and functional connectivity correlates of these putative compensatory mechanisms in the PDD brain. Early education may be a key investment for national governments, especially in low-income countries, to prevent the cognitive deficits of Parkinson's disease along aging, thereby reducing the unbearable social and economic burden.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266094","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":"Retinal vessel diameter reflects altered resting-state fMRI connectivity and cognitive performance: A community-based study.","authors":"Yan Min, Chang Liu, Yanli Zhang, Yuesong Pan, Tao Liu, Hongyu Zhou, Zixiao Li, Yongjun Wang","doi":"10.1007/s11357-025-01667-w","DOIUrl":"https://doi.org/10.1007/s11357-025-01667-w","url":null,"abstract":"<p><p>This study investigated the relationship between fundus microvascular characteristics and the nodal local efficiency (Nle) of brain functional connectivity (FC), as well as their association with cognitive performance in a community-based cohort. A total of 1532 participants from Lishui City, China, were enrolled between May 2017 and September 2019 as part of the polyvascular evaluation for cognitive impairment and vascular events (PRECISE) study. Cognitive performance was assessed using the Montreal Cognitive Assessment-Beijing (MoCA-Beijing), and Nle was derived from resting-state functional magnetic resonance imaging (rs-fMRI). Fundus photography of the left eye was performed to measure microvascular features, including the central retinal arterial equivalent (CRAE), central retinal vein equivalent (CRVE), and their ratio (AVR). Correlations between fundus microvascular indices, cognitive function scores, and brain FC were analyzed. Notably, a wider CRVE was significantly associated with poorer naming scores on cognitive assessments. Several key brain regions, including the left orbital gyrus, right inferior temporal gyrus, left parahippocampal gyrus, bilateral posterior hippocampus, left fusiform gyrus, and left inferior parietal lobule, demonstrated significant correlations between fundus microvascular indices and brain FC. These regions played a crucial role in cognitive function and neural network connectivity. Overall, fundus microvascular characteristics were correlated with the indicators of brain FC related to cognitive function. Our findings suggest that fundus microvascular characteristics may serve as a potential non-invasive biomarker for detecting brain functional alterations linked to cognitive dysfunction in elderly populations.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257952","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":"Quantifying the impact of treatment delays on breast cancer survival outcomes: a comprehensive meta-analysis.","authors":"Zoltan Ungvari, Mónika Fekete, Annamaria Buda, Andrea Lehoczki, Gyöngyi Munkácsy, Paola Scaffidi, Tiziana Bonaldi, János Tibor Fekete, Giampaolo Bianchini, Péter Varga, Anna Ungvari, Balázs Győrffy","doi":"10.1007/s11357-025-01719-1","DOIUrl":"https://doi.org/10.1007/s11357-025-01719-1","url":null,"abstract":"<p><p>Treatment delay in breast cancer care represents a significant concern in oncology, potentially impacting patient survival outcomes. While various factors can contribute to delayed treatment initiation, the quantitative relationship between specific delay intervals and survival remains incompletely understood in breast cancer management. Our study aims to explore the impact of treatment delays on survival outcomes in breast cancer. A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science databases, covering publications from 2000 to 2025. From an initial 6222 records, 18 eligible studies comprising 25 cohorts were included. Hazard ratios (HRs) for all-cause and breast cancer-specific mortality were extracted or calculated for treatment delays of 4, 8, and 12 weeks. Random-effects meta-analyses were performed, and heterogeneity and publication bias were assessed using I² statistics, funnel plots, and Egger's test. This meta-analysis revealed progressively increasing mortality risks with longer treatment delays. For all-cause mortality, HRs increased from 1.12 (95% CI 1.08-1.15) at 4 weeks to 1.25 (95% CI 1.17-1.33) at 8 weeks, and 1.39 (95% CI 1.26-1.53) at 12 weeks. Breast cancer-specific mortality showed more pronounced effects, with HRs of 1.20 (95% CI 1.06-1.36), 1.43 (95% CI 1.11-1.84), and 1.71 (95% CI 1.18-2.49) for 4-, 8-, and 12-week delays, respectively. Analyses combining both survival outcomes demonstrated consistent risk elevation across all time intervals (4 weeks: HR = 1.12, 95% CI 1.09-1.16; 8 weeks: HR = 1.26, 95% CI 1.18-1.34; 12 weeks: HR = 1.41, 95% CI 1.29-1.55). While heterogeneity was significant (I² = 54-92%), no substantial publication bias was detected. Delays in initiating breast cancer treatment are associated with significantly worse survival, particularly for cancer-specific mortality. Each additional 4-week delay increases the hazard of death by over 10%, underscoring the urgency of minimizing delays in diagnosis-to-treatment pathways. These findings have critical implications for healthcare systems, clinical decision-making, and public health policy.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257951","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}