The Journals of Gerontology Series A: Biological Sciences and Medical Sciences最新文献

{"title":"Lifestyle Mediated the Relations of Socioeconomic Status with Risk of Frailty in Middle-Aged and Older Adults: Evidence from Three Prospective Cohorts.","authors":"Qihang Hu,Zhijun Chai,Yue Dong","doi":"10.1093/gerona/glag110","DOIUrl":"https://doi.org/10.1093/gerona/glag110","url":null,"abstract":"BACKGROUNDSocioeconomic status (SES) is a key social determinant of diverse health outcomes. This study examined the association of SES with the risk of frailty among adults aged over 45, and further explored the specific role of lifestyle.METHODSA total of 26,978 individuals from three nationwide cohorts were included in the analysis, with 57.57% of them aged 60 years and older. Frailty was evaluated using the frailty index (FI) constructed from 40 health-related items, and frailty trajectories were identified using group-based trajectory modeling. Latent class analysis was conducted to determine the optimal SES pattern based on occupation, education, and income. The lifestyle score comprised smoking, drinking, exercise, sleep, social participation, and body shape. Cox and Logistic regression models, mediation and joint analysis, and multiple sensitivity analysis were used.RESULTSOver a median follow-up of 7.49 years, 7,636 participants developed frailty. Low SES was a risk factor for frailty (HR = 1.51, 95% CI: 1.43-1.60) and high-ascending frailty trajectory (OR = 1.73, 95% CI: 1.60-1.87). Lifestyle mediated 8.82% of the association for SES and frailty, 8.37% of the association for SES and high-ascending frailty trajectory. Participants exhibiting both low SES and unhealthy lifestyle demonstrated the highest risk of frailty (HR = 2.13, 95% CI: 1.94-2.34) and high-ascending frailty trajectory (OR = 2.55, 95% CI: 2.23-2.92).CONCLUSIONSUnhealthy lifestyle partially mediated the association of low SES with frailty in adults aged over 45. Therefore, simultaneous interventions tailored to socioeconomic and lifestyle factors are needed to prevent frailty.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147753253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intensity Matters: Vigorous Activity is Associated with Lower Pressure-Independent Arterial Stiffness in the UK Biobank.","authors":"Amani M Norling,Alyssa B Dufour,Lewis A Lipsitz","doi":"10.1093/gerona/glag109","DOIUrl":"https://doi.org/10.1093/gerona/glag109","url":null,"abstract":"BACKGROUNDArterial stiffness, a predictor of cardiovascular disease, reflects both structural properties of the arterial wall and load-dependent effects of intra-arterial pressure. Although exercise improves vascular health, its optimal intensity and effects on these stiffness components remain unclear in older adults.METHODSWe analyzed 34,105 UK Biobank participants (mean age 64; 49% female) with finger-derived arterial stiffness index (ASI) and International Physical Activity Questionnaire (IPAQ)-assessed activity. ASI was regressed on mean arterial pressure (MAP) and decomposed into pressure-independent (ASI-PI; residuals) and pressure-dependent (ASI-PD; total minus ASI-PI) components. Multivariable models tested associations with total and intensity-specific MET-minutes, adjusting for demographic, socioeconomic, cardiometabolic, and medication factors.RESULTSHigher overall physical activity was associated with lower total ASI (9.45 ± 2.93 for high activity vs 9.72 ± 2.89 for low; p < 0.001), and lower ASI-PI (-0.01 ± 2.91 for high vs 0.26 ± 2.88 for low vs; p < 0.001). The association between physical activity and ASI-PD was minimal. Each 1-SD higher total MET was associated with lower ASI-PI (β=-0.094, 95% CI -0.119 to -0.068; p < 0.001) but not ASI-PD. In intensity-specific models, vigorous activity was consistently associated with lower ASI-PI (β ≈-0.12; p < 0.001), whereas moderate activity showed modest positive associations, and walking activity was not significantly related. When total activity volume was held constant, vigorous METs were associated with lower ASI-PI, while associations with ASI-PD remained negligible.CONCLUSIONSVigorous activity was consistently associated with lower ASI-PI, suggesting beneficial vascular adaptations to exercise beyond its effects on hemodynamic load.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147753251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunosenescence and Inflammaging: From Pathological Hallmarks to Rejuvenation Strategies.","authors":"Yaoli Hou,Zhiying Zeng,Sheng He,Lili He,Kun Liu,Wen Tang,Deming Wang,Jing Gui,Yan Wang,Wenjie Liu,Ren Jing","doi":"10.1093/gerona/glag108","DOIUrl":"https://doi.org/10.1093/gerona/glag108","url":null,"abstract":"Immunosenescence-the age-related decline of immune function-drives a state of chronic, sterile inflammation termed inflammaging. Far from passive deterioration, this process is actively orchestrated by distinct but interconnected hallmarks: erosion of lymphoid organs, myeloid-biased hematopoiesis, accumulation of immune-evasive senescent cells, and metabolic-epigenetic reprogramming that locks cells into dysfunctional states. These core nodes form a self-perpetuating cycle that propagates pathology across multiple organ systems, fueling neurodegeneration, cancer, musculoskeletal decline, and gut dysbiosis. Critically, the field has transitioned from descriptive phenomenology to mechanism-based intervention. This review synthesizes emerging therapeutic strategies targeting specific nodes of the immunosenescence network. We examine senotherapeutics that sensitize senescent cells for immune clearance, HSC and thymic rejuvenation to restore lymphocyte production, and metabolic-epigenetic interventions to correct intracellular deficits. By integrating these insights, we propose a precision medicine framework that moves beyond broad immunosuppression toward rational combinatorial regimens. This roadmap aims to decouple protective immunity from pathological drivers, extending healthspan and redefining the paradigm of geriatric care.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147739073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex disparities in geriatric syndromes among people 50 years or older receiving care for HIV infection in Mexico (2012-2017): a cross-sectional, observational study","authors":"Yanink Caro-Vega, Pablo F Belaunzarán-Zamudio, Virgilio Hernández-Ruiz, Juan Luis Mosqueda, José A Avila-Funes","doi":"10.1093/gerona/glag107","DOIUrl":"https://doi.org/10.1093/gerona/glag107","url":null,"abstract":"We compared the frequency of geriatric syndromes and comorbidities between women and men over 50 years of age receiving HIV care in Mexico and explore their associated characteristics. This cross-sectional study was conducted from 2012 to 2017 in Mexico. We assessed non-communicable diseases (NCDs), disability, depressive symptoms, neurocognitive impairment, frailty, polypharmacy, falls, and visual and hearing impairment. We compared the prevalence of these syndromes by sex. We fitted multivariate logistic models to identify the association of sex with the presence of NCDs and geriatric syndromes. We enrolled 616 participants, including 114 (18.5%) women. Women were older (median 57 vs 56yo, p = 0.032) and had lower educational attainment (6 vs 12 y, p &amp;lt; 0.001) than men. There were no sex differences in current viral suppression (86% vs 85%, p = 0.78) and median CD4 cell counts (508 vs 458, p = 0.27). Women had a higher prevalence of any NCDs (67% vs 55%, p = 0.02); falls: (44% vs 26%, p &amp;lt; 0.001); depressive symptoms (15% vs 7.6%, p = 0.02), and frailty (9.6% vs 3.2%, p = 0.047) than men. In adjusted analyses, women had higher odds of frailty (aOR 4.38, 95%CI 1.7–11.0, p = 0.01), falls (aOR: 1.97, 95% CI : 1.18—3.28, p &amp;lt; 0.01), NCDs (aOR: 2.03, 95%CI : 1.27—3.23, p &amp;lt; 0.01) and depression (aOR: 2,35, 95%CI: 1.17—4.61, p &amp;lt; 0.01). Older women living with HIV in Mexico experience a high prevalence of overweight/obesity, falls, comorbidity, depressive symptoms, frailty, and disability disproportionately affect women. Women were at higher risk of frailty, falls, comorbidity, and depressive symptoms, independently of age, current CD4 cell counts and education level.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147733277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-sectional and longitudinal associations of an inflammatory aging clock with intrinsic capacity and functional ability in older adults with physical and cognitive impairments: the COGFRAIL cohort.","authors":"Pedro L Valenzuela,Juan Luis Sánchez-Sánchez,Paul Bensadoun,Jean-Marc Lemaître,David Furman,Bruno Vellas,Sandrine Sourdet,Philipe de Souto Barreto","doi":"10.1093/gerona/glag106","DOIUrl":"https://doi.org/10.1093/gerona/glag106","url":null,"abstract":"Chronic inflammation is considered a hallmark of aging, but its association with indicators of healthy aging such as intrinsic capacity (IC) and functional ability remains unknown. We explored the association of an inflammation-based aging clock (iAge) with IC and functional ability in older adults. We used data from the COGFRAIL cohort, including old adults with prefrailty/frailty and mild cognitive and functional impairment. Biological age acceleration was measured at baseline through the inflammatory clock iAge (BAAiAge) was assessed at baseline. Functional ability on basic (BADL) and instrumental activities of daily living (IADL) as well as IC (a composite score [from 0 to 100] including the locomotion, cognition, psychology, sensory and vitality domains) were determined at baseline and on two follow-up visits. A total of 226 participants (82.5 ± 5.1 years, 64% women) had data at baseline, of whom 180 provided data during a 24.5-month follow-up. During the follow-up, a significant decline was observed in BADL (β=-0.4, 95% confidence interval -0.5 to -0.3, p < 0.001), IADL (β=-1.5; 95%CI=-1.7 to -1.2, p < 0.001) and IC (β=-2.0, 95%CI=-3.7 to -0.3, p = 0.025). Although baseline IC was positively associated with both BADL and IADL in cross-sectional (p = 0.002 and p < 0.001) and longitudinal analyses (p = 0.011 and p = 0.070), no association was found between BAAiAge and any of BADL/IADL, IC or IC domains in cross-sectional or longitudinal analyses. BAAiAge seems not to be associated with IC or functional ability in this cohort of very old adults with mild cognitive and functional impairment. Future research should confirm these findings in other cohorts with varying functional status.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147731711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell multiregion dissection of central nervous system aging","authors":"Rui-Ze Niu, Meng-Yuan Zhang, Hui-Hui Yang, Xiao-Feng Zeng, Jia Liu, Tian-Hao Bao","doi":"10.1093/gerona/glag103","DOIUrl":"https://doi.org/10.1093/gerona/glag103","url":null,"abstract":"Central nervous system (CNS) aging is a major risk factor for many disorders, including cerebrovascular disease, neurodegeneration and amyotrophic lateral sclerosis, yet the cellular pathways driving its progression across CNS regions remain poorly defined. Here we present a single-nucleus transcriptomic atlas spanning seven human CNS regions, comprising ∼1.0 million nuclei from 235 post-mortem samples derived from 200 neurologically and psychiatrically normal donors aged 19–101 years. Across regions, we delineate both shared and region-specific features of CNS aging, integrating analyses of transcriptional noise, programmed cell-death signatures, disease associations, metabolic reprogramming and transcriptomic remodeling. We identify cross-regional vulnerability of astroglia, oligodendrocytes, and excitatory and inhibitory neurons, and show that microglial and astrocytic activation represents a broadly conserved aging response across the CNS, highlighting potential targets for intervention. Finally, we present within-dataset proof-of-concept predictive modeling use cases based on aging-associated gene signatures, providing a resource for within-atlas prioritization and hypothesis generation of candidate biomarkers of CNS aging. Together, this work offers a region-by-region map of the aging human CNS and informs the selection of specific cell types and/or regions for future anti-aging strategies.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147733276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Inhaled Aromatherapy on Sleep Quality and Cognitive Function in Older Adults: A Randomized Controlled Trial","authors":"Belçim Ede Sarıkaya, Sebahat Ateş, Tuğba Kaman, Ayşe Arzu Sayın Şakul","doi":"10.1093/gerona/glag105","DOIUrl":"https://doi.org/10.1093/gerona/glag105","url":null,"abstract":"Background Sleep disturbances and cognitive decline frequently coexist in older adults and are associated with adverse health outcomes. Aromatherapy has emerged as a potential non-pharmacological intervention; however, evidence from inhalation-based protocols integrating both subjective and objective sleep assessments remains limited. Methods This single-blind, randomised controlled trial was conducted in a residential care facility in Istanbul between January and June 2024. Sixty participants aged ≥65 years were randomly allocated to an intervention group (n = 30) or a control group (n = 30). The intervention consisted of inhaling a peppermint–palmarosa blend in the morning and a nighttime blend of vetiver, cedarwood, clary sage, petitgrain, and grapefruit oils for 10 minutes daily over 30 days. Outcomes included the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and Blessed Orientation–Memory–Concentration Test, alongside objective sleep parameters obtained from Oppo Watch Free wearable smartwatches using photoplethysmography and accelerometer-based algorithms. Results Compared with the control group, the intervention group demonstrated significant improvements in total sleep time (d = 1.29), REM sleep duration (d = 1.34), and deep sleep (N3) duration (d = 1.47), along with reduced sleep latency (d=–1.12) (all p &amp;lt; 0.001). Daytime sleepiness decreased, and subjective sleep quality improved. Cognitive performance also improved, with significant gains observed in orientation, memory, and concentration, whereas no significant changes were observed in the control group. Conclusions A circadian-aligned, multi-component inhalation aromatherapy protocol may represent a feasible and clinically relevant complementary intervention to improve sleep architecture and cognitive outcomes in older adults residing in residential care settings.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147725918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polypharmacy and Drug-Drug Interactions in Long-Term Care Facilities residents: findings from the Italian Prescription Day Project.","authors":"Alba Malara,Alberto Zucchelli,Caterina Trevisan,Giuseppe Dario Testa,Gilda Borselli,Anna Castaldo,Antonio Cherubini,Raffaele Antonelli Incalzi,Alessandra Marengoni,Alessandro Morandi,Graziano Onder,Dario Leosco,Andrea Ungar, ","doi":"10.1093/gerona/glag104","DOIUrl":"https://doi.org/10.1093/gerona/glag104","url":null,"abstract":"BACKGROUNDMedication prescribing in Long-Term Care Facilities (LTCFs) is characterised by widespread polypharmacy and frequent exposure to potentially clinically relevant drug-drug interactions (DDIs).METHODSData from the Italian Prescription Day in LTCFs 2024, a national multicentre point-prevalence study conducted in 82 LTCFs, were analysed. Prescriptions were classified using the Anatomical Therapeutic Chemical system, and DDIs were identified using an international consensus list. Resident-level variables were assessed using validated tools, and associations with DDI burden were examined using univariate mixed-effects Poisson regression models. Facility-level organisational characteristics were described by centre-level DDI burden.RESULTSThe analysis included 3,174 residents (mean age 84.8 years; 74.1% women), with a mean of 7.7 prescribed drugs. Drugs acting on the nervous system, alimentary tract and metabolism, and cardiovascular system were most frequently prescribed; furosemide, paracetamol, pantoprazole, quetiapine, and macrogol were the most commonly used active substances. Overall, 42.2% of residents were exposed to at least one potentially clinically relevant DDI, most commonly involving centrally acting drugs, cumulative anticholinergic burden, serotonergic combinations, and potassium-related interactions. Higher DDI burden was associated with greater pharmacological complexity, depression, sleep disorders, cardiopulmonary disease, and behavioural and psychological symptoms of dementia, whereas older age, severe cognitive impairment, malnutrition, and dysphagia were associated with fewer DDIs. Facility-level and staffing characteristics showed limited differentiation, with assisted living facilities under-represented at higher DDI burden.CONCLUSIONSPotentially clinically relevant DDIs are common in Italian LTCFs and are primarily associated with resident-level clinical complexity, highlighting targets for medication review and deprescribing to improve medication safety.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147708484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Crossroads between Osteosarcopenia and Intrinsic Capacity - A Narrative Review.","authors":"Nailton José Neto,Guy Hajj-Boutros,Wayne Lok,Miguel G Borda,Konstantinos Prokopidis,Hassan Rammal,Daniel Rivas,Hussein Samhat,Ivan Baltasar-Fernandez,Mahdi Imani,Cristiano Dos Santos Gomes,Oscar Rosas Carrasco,Marc Sim,Julie A Pasco,Julia Chabot,Ana Maria Ayala-Copete,Francisco José García-García,Claire Godard-Sebillotte,Raman Agnihotram,Lana Williams,Anna Andrianova,Robinson Ramirez-Vélez,Emma Connolly,Harmehr Sekhon,Hidenori Arai,Liang-Kung Chen,Andréa Faust,Howard Bergman,Alexandra Papaioannou,Pierrette Gaudreau,Tiago Da Silva Alexandre,Leocadio Rodriguez-Mañas,Ricardo Oliveira Guerra,Gustavo Duque, ","doi":"10.1093/gerona/glag102","DOIUrl":"https://doi.org/10.1093/gerona/glag102","url":null,"abstract":"Intrinsic Capacity (IC) is defined as the composite of physical and mental abilities an individual possesses, encompassing five domains: cognition, psychological health, sensory function, vitality, and locomotion. This construct is central to the World Health Organization's framework for assessing functional ability in older adults. Growing evidence highlights the critical role of the musculoskeletal system in maintaining these domains, while conditions such as sarcopenia, osteoporosis, and their coexistence as osteosarcopenia (OS) are increasingly associated with IC decline. This narrative review compiles current evidence on the modulatory role of muscles and bones in IC and the impacts of sarcopenia, osteoporosis, and OS. Most findings suggest that musculoskeletal tissues influence IC not only through biomechanical functions but also as secretory organs, releasing myokines and osteokines with endocrine, paracrine, and autocrine effects. Among the most studied are brain-derived neurotrophic factor, irisin, osteocalcin, and interleukin-6. Dysregulation of these pathways, along with biomechanical dysfunction and systemic inflammation, links sarcopenia, osteoporosis, and OS to IC impairment. Further research is needed to clarify the specific mechanisms involved, particularly in the sensory and vitality domains, to inform targeted interventions that promote healthy aging.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147695247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunosenescence and CMV-Associated Immune Signatures on SARS-CoV-2 Booster Responses","authors":"Irene Reina-Alfonso, Pablo Álvarez-Heredia, Isabel M Vallejo-Bermúdez, Ana Navas-Romo, Mónica Espinar-García, Fakhri Hassouneh, Ana Belén Pérez, Raquel Tarazona, Rafael Solana, Alexander Batista-Duharte, Juan Molina, Alejandra Pera","doi":"10.1093/gerona/glag095","DOIUrl":"https://doi.org/10.1093/gerona/glag095","url":null,"abstract":"Ageing remodels antiviral immunity, yet its influence on responses to repeated mRNA vaccination is not fully defined. We evaluated humoral and SARS-CoV-2 spike–specific T-cell responses in 41 adults—stratified by age (&amp;lt;50 vs. ≥60 years), sex, prior SARS-CoV-2 infection and cytomegalovirus (CMV) serostatus—before and after a fourth dose of the bivalent BNT162b2 vaccine. Anti-RBD IgG titres increased in nearly all participants, with no measurable impact of age, sex, infection history or CMV status, and baseline titres predicted post-booster antibody levels. In contrast, cellular immunity showed clear heterogeneity across ageing-related variables. Although the booster enhanced IFN-γ production and reduced TNF-α-associated inflammatory activity at the cohort level, older adults and males exhibited significantly lower post-boost frequencies of IFN-γ–producing CD4+ T cells. Prior SARS-CoV-2 infection was associated with attenuated CD4+ recall responses, whereas infection-naïve and female participants showed the strongest functional gains. Immunosenescence markers were associated with reduced cellular responsiveness. CMV-related immune remodelling—including higher anti-CMV IgG levels and expansions of differentiated CD8+ subsets—correlated with diminished IFN-γ responses in CD4+ and CD8+ T cells after boosting, suggesting that chronic CMV imprinting constrains heterologous antiviral immunity even in mid-adult life. Humoral and cellular changes were largely uncoupled, supporting the need to evaluate both arms of adaptive immunity. These findings indicate that while a fourth bivalent BNT162b2 dose reliably reinforces humoral immunity across ages, the magnitude and quality of cellular responses are shaped by age, sex, infection history and CMV-associated immunosenescence. Incorporating immune-ageing markers into vaccination strategies may improve booster efficacy in older populations.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147702429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}