Frontiers in aging最新文献

{"title":"Mesenchymal stem cell senescence as a potency brake: causes, consequences, and cures.","authors":"Sen Zhou, Yu Xie, Yanjie Guo, Yufu Zhang, Yusi Liu","doi":"10.3389/fragi.2026.1929624","DOIUrl":"10.3389/fragi.2026.1929624","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) are widely investigated for regenerative medicine, tissue repair, immunomodulation, and selected cancer-related applications because of their multilineage differentiation potential, paracrine activity, immunoregulatory properties, and capacity to home to sites of injury. However, the therapeutic potential of MSCs depends not only on their tissue source or surface-marker expression but also on their functional state. MSC senescence is not a single phenotypic alteration; rather, it reflects the combined effects of persistent DNA damage response activation, disruption of mitochondrial and metabolic homeostasis, remodeling of epigenetic and secretory networks, and loss of proteostasis. Collectively, these changes drive MSCs toward reduced proliferative capacity, dysregulated paracrine signaling, impaired immunomodulatory activity, and diminished tissue-repair potential, thereby compromising cell-product potency and batch-to-batch consistency. This review summarizes the molecular mechanisms underlying MSC senescence, its source-specific functional consequences, and emerging rejuvenation strategies, with an emphasis on MSC quality control, potency assessment, and clinical translation.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"7 ","pages":"1929624"},"PeriodicalIF":4.9,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148868174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baseline cognitive status and adherence are associated with cognitive change following language learning in older adults: an exploratory study.","authors":"Ladan Ghazi Saidi, Zoha Deldar, Ricardo Carrillo-Meza, Kiley Allgood, Alison Gansemer, Mariah Gentz, Amor Sofia Calderón-Hernández, Yunju Im, Cary R Savage, Douglas H Schultz","doi":"10.3389/fragi.2026.1734620","DOIUrl":"10.3389/fragi.2026.1734620","url":null,"abstract":"<p><strong>Introduction: </strong>Given cognitive benefits observed in lifelong bilinguals, a key question is whether L2 learning can boost cognition in later life.</p><p><strong>Methods: </strong>In a pre-post intervention study, we assessed cognitive effects of learning a new language in older adults as measured by global cognition and domain-specific cognitive tests.</p><p><strong>Results and discussion: </strong>While the MMSE, MoCA, and domain-specific measures (Stroop, Simon, nonword repetition, phonemic fluency, and semantic fluency) did not show significant whole-group pre-post change, a number of individual participants improved on all or some of these measures. Further, both linear regression and machine learning models indicated that participants with lower baseline scores on the MMSE, MoCA, phonemic fluency, and semantic fluency showed greater improvement in post-intervention measurements, reflecting greater cognitive gains, with phonemic fluency emerging as the best predictor of intervention outcome. A <i>post hoc</i>, adherence-sensitive analysis further indicated a +1.225-point MoCA advantage in completers relative to non-completers, consistent with an adherence-associated pattern. Machine learning analyses confirmed that cognitive gains were heterogeneous across participants and that the most responsive outcomes were reaction-time-based executive measures, particularly the Stroop task and Symbol Digit Substitution Test (SDST). Cluster analysis showed that the top improver profile combined lower baseline executive performance with markedly higher engagement and lesson completion.</p><p><strong>Conclusion: </strong>These results provide preliminary evidence that engagement in a structured and sustained L2-learning program may be associated with measurable pre-post cognitive changes in some older adults, especially when baseline performance leaves room for improvement. Further, high intervention adherence and engagement are critical to the extent of cognitive benefits derived from L2 learning interventions. Clinically, structured language learning programs that emphasize adherence, dose, and fidelity appear promising for older adults, especially those with emerging decline. These results are noteworthy, given the scarcity of effective options to improve cognitive health in aging, and the fact that L2 learning is low-cost and broadly accessible.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"7 ","pages":"1734620"},"PeriodicalIF":4.9,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148868243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From obesity to healthy longevity: a consensus-based clinical framework for diagnosis, staging, and treatment.","authors":"Silvija Canecki-Varžić, Ines Bilić-Ćurčić, Maja Bakula, Tomislav Bulum, Maja Čavlović, Diana Delić-Brkljačić, Tamara Turk Wensveen, Daniela Fabris-Vitković, Dubravka Jurišić-Eržen, Sanja Klobučar, Kristina Kljajić, Mladen Krnić, Blaženka Miškić, Nataša Moser, Božidar Novoselović, Ivan Pećin, Tina Tičinović-Kurir, Jelena Vučak-Lončar, Marina Gradišer, Maja Cigrovski Berković, Gorana Mirošević, Kristina Selthofer-Relatić, Miro Bakula","doi":"10.3389/fragi.2026.1834323","DOIUrl":"10.3389/fragi.2026.1834323","url":null,"abstract":"<p><strong>Background: </strong>Obesity is a chronic, progressive, relapsing disease characterized by excess or dysfunctional adiposity that impairs health and contributes to multimorbidity, disability, and reduced life expectancy. Contemporary international frameworks recommend moving beyond BMI-only definitions toward disease-based diagnostic models that integrate adiposity, complications, and functional status. Croatia faces a high prevalence of obesity alongside constrained healthcare resources and limited reimbursement for modern pharmacotherapy, highlighting the need for nationally adapted clinical guidance.</p><p><strong>Methods: </strong>This position statement was developed using a modified Delphi consensus process involving 23 multidisciplinary experts from academic and clinical institutions across Croatia. Consensus statements were derived from contemporary international guidelines, randomized controlled trials, and meta-analyses. Evidence quality and recommendation strength were graded using an adapted GRADE-based framework.</p><p><strong>Results: </strong>The document establishes a Croatia-specific framework for the diagnosis, staging, and management of obesity. Diagnosis requires confirmation of excess adiposity with evidence of clinical risk or dysfunction and integrates anthropometric measures with metabolic, mechanical, psychological, and functional domains. A staging system aligned with EASO and Lancet frameworks guides treatment intensity according to disease severity. Management is based on four pillars: lifestyle therapy, psychological support, pharmacotherapy, and metabolic/bariatric surgery. Pharmacological treatment is stage-based and comorbidity-driven, prioritizing agents with proven organ-protective effects. Special considerations are provided for older adults, emphasizing preservation of muscle mass, functional capacity, independence, and quality of life. Long-term structured follow-up is recommended for all patients, reflecting the chronic disease model of obesity.</p><p><strong>Conclusion: </strong>This position statement provides an evidence-based, nationally adapted clinical framework that aligns obesity management with modern chronic disease standards. By integrating disease staging, individualized therapy, and long-term care, it supports precision treatment across the lifespan and emphasizes obesity management as a key strategy for preventing complications, reducing disability, and promoting healthy longevity.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"7 ","pages":"1834323"},"PeriodicalIF":4.9,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13522667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148851477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomics of aging: biomarkers for physiological systems and diseases.","authors":"Ying Luo, Yu-Lin Xiao, Jie-Hua Chen, Hongjue Wang, Shuhong Luo, Hua Dong, Ruo-Pan Huang","doi":"10.3389/fragi.2026.1895104","DOIUrl":"10.3389/fragi.2026.1895104","url":null,"abstract":"<p><p>Aging is a progressive, multisystem process characterized by declining physiological resilience and increased susceptibility to chronic diseases. Recent advances in high-throughput proteomics have enabled comprehensive mapping of age-related changes across circulating proteins, revealing dynamic and non-linear trajectories that reflect biological rather than chronological aging. This review synthesizes current evidence on proteomic biomarkers across major physiological systems, including the immune, metabolic/endocrine, cardiovascular, musculoskeletal, and nervous systems, and highlights shared molecular signatures that underpin multisystem decline. Robust biomarkers such as IL-6, CRP, CXCL9/10, GDF15, IGF-1, VCAM-1, NT-proBNP, NfL, and GFAP consistently track inflammatory activation, mitochondrial and metabolic stress, extracellular matrix remodeling, and neuro-glial injury. Large population cohorts demonstrate that proteomic aging clocks, leveraging dozens to hundreds of circulating proteins, can predict frailty, multimorbidity, organ-specific biological age, and mortality with high accuracy. Emerging evidence suggests that a limited set of cross-system \"protein aging modules\"-including inflammatory cytokines, chemokines, complement proteins, and ECM-modifying enzymes-may serve as integrative readouts and potential regulators of aging biology. We discuss methodological advances, system-specific mechanisms, and translational applications of proteomic aging models. Together, these findings position proteomics as a powerful tool for quantifying biological age, identifying early disease risk, and guiding precision interventions to promote healthier aging.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"7 ","pages":"1895104"},"PeriodicalIF":4.9,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13522669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148851639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-related differences in BMD response during three years of denosumab treatment.","authors":"Koji Ishikawa, Tomoyuki Asada, William Richardson, Choiselle Marius, Mahoko Ishikawa, Tuyet Nguyen, Philip Varnadore, Soji Tani, Peter Passias, Benjamin Aaron Alman","doi":"10.3389/fragi.2026.1892852","DOIUrl":"10.3389/fragi.2026.1892852","url":null,"abstract":"<p><strong>Introduction: </strong>Denosumab increases bone mineral density and reduces fracture risk in patients with osteoporosis. However, whether BMD response to denosumab differs by age, particularly during longer term treatment, remains unclear. This study investigated the association between baseline age and BMD gain during 3 years of denosumab treatment in patients with osteoporosis.</p><p><strong>Methods: </strong>This retrospective study included patients with osteoporosis who were treated with denosumab. DXA-based BMD and bone turnover markers were followed for up to 3 years. Percent BMD gain from baseline was evaluated. The longitudinal association between baseline age and %BMD gain was assessed using multivariable linear mixed effects models for the lumbar spine and total hip. Analyses were performed in the treatment naive cohort and the overall cohort according to prior osteoporosis treatment status.</p><p><strong>Results: </strong>A total of 255 patients were included, of whom 110 were treatment naive. In multivariable linear mixed effects models, older baseline age was associated with smaller lumbar spine %BMD gain in the treatment naive cohort at both 1 and 3 years. Each 1 year increase in age was associated with a 0.187 percentage point lower lumbar spine %BMD gain at 1 year and a 0.293 percentage point lower gain at 3 years (1 year: β = -0.187, p = 0.006, 3 years: β = -0.293, p = 0.031). In contrast, baseline age was not significantly associated with total hip %BMD gain in the treatment naive cohort (1 year: β = -0.011, p = 0.826, 3 years: β = 0.028, p = 0.727). In the overall cohort, baseline age was not significantly associated with %BMD gain at either skeletal site.</p><p><strong>Conclusion: </strong>Older baseline age was associated with a modestly smaller lumbar spine BMD gain in treatment-naive patients, whereas no statistically significant age-related association was observed at the total hip. These findings indicate a modest, site-specific association between baseline age and BMD gain in treatment-naive patients.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"7 ","pages":"1892852"},"PeriodicalIF":4.9,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13518595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148842282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intelligent health promotion system-based construction and implementation of exercise intervention for older adults with frailty and prefrailty.","authors":"Mengya Liu, Li Zhang, Qin Huang, Xiaoli Zhu, Yu Wang, Lin Zhu","doi":"10.3389/fragi.2026.1780093","DOIUrl":"10.3389/fragi.2026.1780093","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Frailty in the elderly population is increasing, and the development of high-quality clinical practice guidelines or consensuses can guide medical staff to better provide health services for frail elderly individuals. In recent years, scholars at home and abroad have actively explored exercise intervention management in elderly individuals with frailty or prefrailty. How to rapidly generalize interventions with \"known and definite effects\" for the community-dwelling frail elderly population is the core issue of the research on frailty. There is a lack of study regarding whether digital interventions can improve exercise adherence for older adults with frailty and prefrailty.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;In accordance with the Comprehensive Framework for Implementation Research (CFIR), this study implemented scientific strategies for exercise interventions for elderly people with community frailty and prefrailty. Empirical research was conducted via the cloud platform of the home‒community integration system to provide a theoretical basis for improving the physical, psychological and social frailty of frail elderly people and reducing the incidence of adverse outcomes caused by frailty in the community.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Qualitative and quantitative research methods were fully integrated. Semistructured interviews were conducted with 64 older adults who designated family doctors and 44 community workers in the community to identify the regular exercise adherence of frail or prefrail older adults as well as the promoting and hindering factors of community workers in the implementation of scientific exercise interventions. Following the guidance of the Comprehensive Framework for Implementation Research (CFIR), scientific exercise intervention strategies for frail elderly people in the community were implemented. The control group received routine nursing, and the intervention group received a scientific nursing intervention. After 3 months of intervention, the effects of the strategy on implementation outcomes (feasibility, acceptability, fidelity, etc.), intervention outcomes (physical function, emotional state, social support, self-efficacy), process outcomes (skills or cognition), and resource utilization in older adults with frailty or prefrailty were evaluated.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In the qualitative interviews conducted with CFIR as the theoretical guiding framework, a total of 22 influencing factors, 12 promoting factors and 10 hindering factors in 4 areas were identified to construct scientific strategies for implementation。The implementation results revealed that the feasibility (P = 0.003), acceptability (P = 0.002) and fidelity (P = 0.001) of the intervention group were significantly better than those of the control group. The intervention results revealed that, compared with those in the control group, physical fitness (gait: P = 0.016; balance: P &lt; 0.001; grip strength: P &lt; ","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"7 ","pages":"1780093"},"PeriodicalIF":4.9,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13518563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148842248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physical exercise for prevention of dementia study: a 48-month randomized controlled trial.","authors":"Enzo Iuliano, Giovanni Fiorilli, Antonella Angiolillo, Graziamaria Corbi, Giulia Di Martino, Santina Ciccotelli, Carlo Della Valle, Giuseppe Calcagno, Alessandra di Cagno, Alfonso Di Costanzo","doi":"10.3389/fragi.2026.1847451","DOIUrl":"10.3389/fragi.2026.1847451","url":null,"abstract":"<p><strong>Background: </strong>Although multimodal exercise interventions are recognized for their potential to attenuate age-related cognitive decline, the current literature lacks longitudinal depth. Specifically, robust randomized evidence addressing the long-term efficacy of structured training protocols remains limited. This single-blind RCT involved 882 community-dwelling older adults categorized as healthy, having subjective memory complaints (SMCs), or having mild cognitive impairment (MCI).</p><p><strong>Methods: </strong>Participants were randomized to an experimental group (EG), performing 48 months of supervised moderate-to-high-intensity multimodal training (aerobic, resistance, and stretching), or to a control group (CG), maintaining usual habits. The primary outcome was the 48-month change in Mini-Mental State Examination (MMSE) scores. Secondary outcomes were scores on eight neuropsychological tests assessed at 12, 24, 36, and 48 months. A linear mixed-effects model analysis with repeated measures (LMM) was used to evaluate significant differences between the CG and EG.</p><p><strong>Results: </strong>In the final analysis of 674 participants, healthy participants (between-group effect: <i>p</i> = 0.008; η² _p = 0.007; time*group interaction: <i>p</i> < 0.001; η² _p = 0.025) in the EG showed significantly higher MMSE scores than those in the CG. SMC participants in the EG also showed higher MMSE scores than those in the CG (between-group effect: <i>p</i> = 0.052; η² _p = 0.004; time*group interaction: <i>p</i> < 0.001; η²p = 0.031), although the between-group difference only approached statistical significance. Similarly, healthy and SMC participants in the EG demonstrated significantly better performance in the secondary outcomes of memory, attention, and reasoning than those in the CG. The sample size of the MCI group was insufficient to allow for conclusive statistical analyses.</p><p><strong>Conclusion: </strong>A 48-month multicomponent exercise program significantly improved cognitive performance in healthy and SMC older adults. Structured physical activity may effectively slow cognitive decline.</p><p><strong>Clinical trial registration: </strong>https://clinicaltrials.gov/study/NCT02236416. Identifier number: NCT02236416.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"7 ","pages":"1847451"},"PeriodicalIF":4.9,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13501581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148814945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The relationship between sarcopenia detected in newly diagnosed lung cancer patients and serum levels of IL6, IGF-1 and myostatin.","authors":"Kamil Süzer, Utku Oflazoglu, Leyla Demir, Sinan Unal, Zeynep Gulsum Guc, Yasar Yildiz, Furkan Oguzhan Karalar, Yuksel Kucukzeybek, Ahmet Alacacioglu","doi":"10.3389/fragi.2026.1800359","DOIUrl":"https://doi.org/10.3389/fragi.2026.1800359","url":null,"abstract":"<p><strong>Aim: </strong>Sarcopenia can result from many factors, including cancer, and is a consequence of quantitative and qualitative deterioration in skeletal muscle mass. Although there are some hypothetical explanations for sarcopenia, the underlying mechanisms of this condition have not been clearly defined in cancer patients. In this study, we aimed to investigate the association between sarcopenia and serum levels of myostatin, insulin-like growth factor-1 (IGF-1), and interleukin-6 (IL-6) in patients with newly diagnosed lung cancer.</p><p><strong>Material and method: </strong>This cross-sectional prospective study included patients with newly diagnosed metastatic non-small cell lung cancer (NSCLC), who were categorized into two groups based on the presence or absence of sarcopenia. Body composition and muscle mass were evaluated using bioelectrical impedance analysis (BIA), and body mass index (BMI) was calculated. Handgrip strength was measured using a handheld dynamometer. Serum levels of myostatin, insulin-like growth factor-1 (IGF-1), and interleukin-6 (IL-6) were analyzed from fasting venous blood samples to assess their association with sarcopenia.</p><p><strong>Results: </strong>A total of 69 patients were included in the study. The patients' ages ranged from 49 to 75 years. Thirty-four of these patients were sarcopenic and thirty-five of them were non-sarcopenic. Eighty-seven percent (60) of the patients included in the study were male. While myostatin and IL-6 levels were higher in the sarcopenic patient group, IGF-1 mean levels were lower. In the non-sarcopenic patient group, the median levels of myostatin, IL-6, and IGF-1 were 11.82 ng/mL, 1.17 pg/mL and 23.51 ng/mL, respectively. In the sarcopenic patient group, the median levels of myostatin, IL-6, and IGF-1 were 16.76 ng/mL, 7.42 pg/mL and 12.82 ng/mL, respectively (p < 0.001, p < 0.01, and p < 0.001, respectively). Spearman's correlation analysis between SMI (skeletal muscle mass index) and myostatin, IGF-1 and IL-6 levels showed a negative correlation of SMI with myostatin and IL-6, and a positive correlation with IGF-1 [(r = -0.436, p < 0.001) (r = -0.520, p < 0.001), (r = 0.219, p:0.071) respectively]. When a logistic regression model was constructed with sarcopenia status as the dependent variable and myostatin, IGF-1, IL-6, and ECOG performance parameters as independent variables, myostatin and IGF-1 were identified as independent predictors [OR: 1.332, CI: (1.128-1.574), p: 0.001; OR: 0.926, CI: (0.874-0.982), p: 0.01, respectively].</p><p><strong>Conclusion: </strong>We found a significant correlation between sarcopenia and myostatin, IGF-1 and IL-6 in patients with lung cancer. We suggest that myostatin, IGF-1, and potentially IL-6 may serve as reliable markers for sarcopenia in cancer patients. We believe that these findings may encourage future prospective studies investigating the potential relevance of myostatin, IGF-1 and IL-6 as markers of sarcopenia.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"7 ","pages":"1800359"},"PeriodicalIF":4.9,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148802071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in the pathogenesis of degenerative knee osteoarthritis: a comparative transcriptomics analysis.","authors":"Ayobami S Ogunsola, Davis J Brady, Jeffrey A Foster, Marcel G Brown, Molly A Hartzler, Maxwell K Langfitt, John S Shields, Xue Ma","doi":"10.3389/fragi.2026.1875372","DOIUrl":"https://doi.org/10.3389/fragi.2026.1875372","url":null,"abstract":"<p><strong>Introduction: </strong>Osteoarthritis (OA) is one of the leading diseases worldwide and is expected to continue to rise in prevalence. Epidemiological studies on OA have long shown a sex discrepancy between males and females, with females consistently showing greater rates of OA. There are numerous theories about why this might be the case; however, the discrepancy is still poorly understood.</p><p><strong>Methods: </strong>In this study, two cohorts of patients with Kellgren-Lawrence grade IV knee OA were grouped based on sex and analyzed to decipher transcriptomic differences. The first cohort was a GSE114007 public dataset from the NCBI Gene Expression Omnibus (GEO) database, while the second cohort was from our institution. For each cohort, differential gene expression analysis (DEG), principal component analysis (PCA), functional enrichment analyses (Kyoto Encyclopedia of Genes and Genomes, Gene Set Enrichment Analysis, and Gene Ontology), and protein-protein interaction (PPI) analysis were performed.</p><p><strong>Results: </strong>In the GSE114007 cohort, XIST gene was the sole significant DEG at the genome-wide level. In contrast, our local cohort showed 109 DEGs between males and females. Functional enrichment analyses in both the GSE114007 and local cohorts showed female upregulation of inflammatory pathways, while the local cohort also showed female increases in protein synthesis and metabolic pathways, with males showing greater enrichment of structural and tissue remodeling pathways. PPI analysis showed female upregulation of three clusters of interacting proteins related to protein synthesis and translation, energy metabolism, oxidative phosphorylation, cell communication, and tissue remodeling.</p><p><strong>Discussion: </strong>Our analyses suggest that the pathogenesis of OA in women may be related to inflammatory and metabolic mechanisms, whereas OA in men may be driven by structural pathways involved in stress and remodeling. Hence, sex specific therapeutic strategies may be necessary to effectively target the pathobiological mechanisms driving OA in males and females.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"7 ","pages":"1875372"},"PeriodicalIF":4.9,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148802122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence and machine learning in immunosenescence: from biomarker discovery to clinical translation.","authors":"Xi Chen, Yan Han, Ruixuan Zhang, Xinyang Huang, Jinwu Liu, Hanxu Xie, Ling Teng, Chen Han, Ziqi He, Zimeng Yang, Shihan Huang, Jianhui Yan","doi":"10.3389/fragi.2026.1851261","DOIUrl":"https://doi.org/10.3389/fragi.2026.1851261","url":null,"abstract":"<p><p>The global population is undergoing unprecedented aging, with immunosenescence established as a core upstream driver of nearly all age-related chronic diseases, imposing a massive global clinical burden. For decades, immunosenescence research has been mired in three persistent translational bottlenecks: inability to capture interindividual immune aging heterogeneity, failure to decode complex multi-layered biological regulatory networks, and inefficient therapeutic development pipelines. Artificial intelligence (AI) and machine learning (ML) have emerged as promising solutions to these bottlenecks, yet existing literature fails to systematically bridge AI technical advances with clinical immunology practice, and often does not distinguish proof-of-concept evidence from the steps needed for clinical use. This review provides a holistic, critical overview of AI/ML applications across the full translational spectrum of immunosenescence research, from mechanistic discovery, biomarker development, diagnostic innovation to therapeutic development and personalized medicine. We further analyze unresolved technical, ethical, and regulatory barriers to clinical translation, including underrecognized fundamental flaws in current model design. Emerging AI technologies to address these limitations are outlined, alongside a clinically realistic translational roadmap and key future research trends. This review fills critical gaps in existing literature, providing a rigorous framework to shift the field from \"AI for AI's sake\" to clinical utility-focused research, ultimately advancing healthy aging interventions.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"7 ","pages":"1851261"},"PeriodicalIF":4.9,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148801784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}