The journals of gerontology. Series A, Biological sciences and medical sciences最新文献

{"title":"Association between air pollution and the risk of cognitive frailty: insights from two population-based studies in the United Kingdom and China.","authors":"Linghui Deng, Yuwei Wu, Shi Qiu, Giorgia Melli, Jirong Yue, Guanru Li, Jiahao Zuo, Ruiyao Ma, Xinqing Hao, Weichao Huang, Chuzhong Wei, Yumin Jin, Xianghong Zhou, Zilong Zhang, Bin Zeng, Yuxiao Li, Sophia Zuoqiu, Birong Dong","doi":"10.1093/gerona/glag128","DOIUrl":"10.1093/gerona/glag128","url":null,"abstract":"<p><strong>Background: </strong>Cognitive frailty, encompassing cognitive decline and physical frailty, is an increasing concern in aging populations. Air pollution is associated to several health outcomes.</p><p><strong>Methods: </strong>Data of 62 098 participants from UK Biobank cohort and 3321 participants from West China Health and Aging Trend (WCHAT) cohort were subjected to cross-sectional analyses to evaluate the association between the investigating parameters, and prospective analyses were performed in the UK Biobank.</p><p><strong>Results: </strong>Exposure to ambient air pollution was significantly associated with increased risk of cognitive frailty in middle-aged and older adults. In the UK Biobank prospective analysis, exposures to NOx (hazard ratio [HR] 1.11, 95% confidence interval [CI], 1.01-1.23; p = .0357), nitrogen dioxide (HR 1.14, 95% CI, 1.00-1.30; p = .0428), and PM2.5 (HR 1.18, 95% CI, 1.04-1.34; p = .0091) were consistently associated with cognitive frailty. Cross-sectional analyses in the UK Biobank supported these findings, with additional positive associations observed for PM10 (odds ratio [OR] 1.02, 95% CI, 1.00-1.05; p = .0374). In WCHAT cohort, ozone exposure showed the most consistent associations across exposure windows and models (3-year: OR 1.29, 95% CI, 1.14-1.45; p < .0001; 5-year: OR 1.34, 95% CI, 1.20-1.50; p < .0001). Additionally, PM2.5 exposure within the 1-year exposure window also demonstrated a statistically significant association (Q3: OR 1.53, 95% CI, 1.04-2.25; p = .0327). Stratified analyses suggested stronger associations among adults ≥60 years, females, and overweight individuals.</p><p><strong>Conclusions: </strong>Higher air pollution levels were significantly associated with increased cognitive frailty risk, emphasizing on developing public health interventions to reduce air pollution exposure, especially among vulnerable populations.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147978298","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":"Trajectories of cognitive performance in the six months after hospitalization with COVID-19 among community-dwelling older adults.","authors":"Judy Li, Gail McAvay, Tamar A Kaminski, Thomas M Gill, Andrew B Cohen, Lauren E Ferrante, Alexandra M Hajduk","doi":"10.1093/gerona/glag118","DOIUrl":"10.1093/gerona/glag118","url":null,"abstract":"<p><strong>Background: </strong>Older adults are vulnerable to post-COVID-19 cognitive impairment (CI). This study aimed to characterize cognitive trajectories among older adults in the 6 months after hospitalization with COVID-19 and identify associated factors.</p><p><strong>Methods: </strong>This prospective longitudinal cohort study included 311 community-dwelling adults age ≥60 years hospitalized with COVID-19 and enrolled in the VALIANT (COVID-19 in Older Adults: A  Longitudinal Assessment) study between June 2020 and June 2021. Cognitive performance was assessed using the Montreal Cognitive Assessment 5-min protocol during hospitalization and at 1, 3, and 6 months post-discharge. Sociodemographic and clinical data were collected via baseline interviews and the electronic health record. Cognitive trajectories and their associated factors were identified using discrete mixture models and multinomial logistic regression.</p><p><strong>Results: </strong>Mean age was 71.4 ± 8.4 years (54.6% women, 3.7% with documented evidence of pre-admission CI, 41% with in-hospital CI). Three cognitive trajectories were identified at 6 months post-discharge: persistent moderate impairment (14.1%), borderline impairment (47.5%), and no impairment (38.4%). Factors associated with membership in persistent moderate or borderline impairment trajectories, relative to the no impairment trajectory, were in-hospital cognitive performance, delirium, hearing impairment, and multimorbidity. Pre-admission CI perfectly predicted membership in the no impairment trajectory (ie, zero participants in the no impairment trajectory had pre-admission CI).</p><p><strong>Conclusions: </strong>Distinct cognitive trajectories of persistent moderate impairment, borderline impairment, and no impairment emerged among older adults during the 6 months after hospitalization for COVID-19. Trajectory membership was predicted by several clinical factors, screening for which may be useful in predicting cognitive trajectories after COVID-19 hospitalization.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147871234","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":"Association of deep learning-derived temporalis sarcopenia with mortality in acute ischemic stroke.","authors":"Joshua Ron Onichino, Ding Yi Zhang, Miguel Trottier, Lorne Rosenbloom, Jonathan Afilalo","doi":"10.1093/gerona/glag149","DOIUrl":"10.1093/gerona/glag149","url":null,"abstract":"<p><strong>Background: </strong>Sarcopenia is associated with mortality following acute ischemic stroke (AIS), but diagnosis is time-consuming. Computed tomography (CT) measures of temporal muscle volume (TMV) and density (TMD) can be automatically extracted from existing scans using deep learning (DL). This study sought to demonstrate the incremental value of DL-derived TMV and TMD from CT scans on AIS mortality and length of stay (LOS).</p><p><strong>Methods: </strong>In this retrospective, single-center cohort study, consecutive AIS patients admitted from 2014 to 2023 were included. TMV and TMD were quantified on admission CT scans by a novel DL model and represented as continuous or categorical variables. Patients were classified as non-sarcopenic, pre-sarcopenic (low TMV or TMD), or sarcopenic (low TMV and TMD) using 5th-percentile thresholds derived from 50 healthy adults. The primary outcome was 30-day all-cause mortality. Secondary outcomes were 365-day all-cause mortality and LOS. Multivariable logistic and linear regression were used.</p><p><strong>Results: </strong>The cohort consisted of 2285 patients with 1151 (50%) females, and a mean (SD) age of 74.7 (13.7) years. There were 877 (38%) non-sarcopenic, 838 (37%) pre-sarcopenic, and 570 (25%) sarcopenic patients. Adjusted ORs (95% CIs) for 30-day mortality were 2.70 (1.64-4.46) and 2.91 (1.72-4.91) for pre-sarcopenia and sarcopenia. Findings were consistent across secondary outcomes. The association between sarcopenia and mortality was preserved after adding the Hospital Frailty Risk Score (HFRS) to the models. Findings were consistent in sensitivity analyses using cohort-derived threshold definitions.</p><p><strong>Conclusions: </strong>TMV and TMD extracted using a novel DL model were incrementally predictive of AIS mortality.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13290469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148159668","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":"Effects of a short-term multicomponent functional exercise program on the serum proteome: an exploratory study in hospitalized older adults.","authors":"Maite Izco-Cubero, Mercedes Lachén-Montes, Chenhui Chenhuichen, Bernardo Abel Cedeno-Veloz, Icíar Echeverría-Beistegui, Fabricio Zambom-Ferraresi, Fabiola Zambom-Ferraresi, María Luisa Fernández-González de la Riva, Patricia Álvarez-Rodríguez, Enrique Santamaría, Nicolás Martínez-Velilla","doi":"10.1093/gerona/glag111","DOIUrl":"10.1093/gerona/glag111","url":null,"abstract":"<p><p>Hospitalization in older adults often leads to disability in daily living activities, thereby increasing the risk of functional and cognitive impairments. Thisrandomized controlled trial analyzed the serum protein profile of patients admitted to an acute geriatric unit who engaged in supervised multicomponent functional exercise program compared with a control group. Potential protein biomarkers were assessed using the Olink serum proteomics platform employing two predefined panels: Cardiometabolic and Inflammation. Notably, the short-term exercise intervention was associated with moderate but consistent changes in the serum proteome. Nominal differences (p < .05, unadjusted) were observed for amyloid beta precursor-like protein 1 (APLP1), complement C1q tumor necrosis factor-related protein 1 (C1QTNF1), interleukin-8 (CXCL8), interleukin-7 (IL-7), M-phase phosphoprotein 8 (MPHOSPH8), neurotrophin 3 (NTF3), tissue-type plasminogen activator (PLAT), SFRS1-interacting protein (PSIP1), pleiotrophin (PTN), cardiac-type troponin I (TNNI3), and von Willebrand factor (vWF); conversely, levels of CD40 ligand (CD40LG) were reduced. These findings suggest that short-term multicomponent functional exercise during acute hospitalization can induce changes in the serum proteome. These molecular alterations provide exploratory insights into the biological processes associated with the functional benefits observed following the intervention in hospitalized older adults.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13242929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147825372","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":"Uric acid to high-density lipoprotein cholesterol ratio as a novel biomarker for sarcopenia: a national study with machine learning insights.","authors":"Ruonan Yang, Zesong Cheng, Pei Yang, Xiujuan Yang, Wanlin Liao, Siwei Zhai","doi":"10.1093/gerona/glag132","DOIUrl":"10.1093/gerona/glag132","url":null,"abstract":"<p><strong>Background: </strong>Sarcopenia is a major age-related health burden. Although the uric acid to high-density lipoprotein cholesterol ratio (UHR) has been linked to sarcopenia, its underlying pathways and clinical utility remain unclear.</p><p><strong>Methods: </strong>We analyzed 9853 adults from the China Health and Retirement Longitudinal Study. Sarcopenia was defined by Asian Working Group for Sarcopenia 2019 Consensus criteria. We assessed the UHR-sarcopenia relationship using multivariable logistic regression and restricted cubic splines. Mediation analyses examined roles of insulin resistance (TyG index) and renal function (eGFR). Five machine learning algorithms were developed and evaluated in training (70%) and testing (30%) sets. Feature selection was performed using Boruta and LASSO, and model interpretability was assessed using SHapley Additive exPlanations (SHAP).</p><p><strong>Results: </strong>Higher UHR was independently associated with lower odds of sarcopenia, with an adjusted odds ratio per-standard deviation increase of 0.75 (95% CI: 0.69-0.81; p < .001), and showed a nonlinear dose-response relationship. UHR correlated with better handgrip strength and chair-stand performance. The TyG index and eGFR mediated 16.44% and 2.03% of this association, respectively. In machine learning analyses, ROC-AUC values ranged from 0.73 to 0.77, with XGBoost showing the best performance. SHAP analysis based on the XGBoost model further identified UHR as the second most important predictor of sarcopenia, following age.</p><p><strong>Conclusions: </strong>Higher UHR was associated with lower sarcopenia risk in Chinese middle-aged and older adults, partly through metabolic and renal pathways. UHR may serve as a simple biomarker for sarcopenia risk stratification.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13264432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148007776","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":"Mitochondrial Dysfunction in Myoblasts: A TSPO-Dependent Mechanism of Sarcopenia.","authors":"Peng Zhang, Hongyu Zheng, Zhao Lin, Hanhao Dai, Minjuan Zhang, Linhai Yang, Zhibo Deng, Chao Song, Yibin Su, Rongsheng Zhang, Guoyu Yu, Jun Luo, Jie Xu, Fenqi Luo","doi":"10.1093/gerona/glag145","DOIUrl":"https://doi.org/10.1093/gerona/glag145","url":null,"abstract":"<p><p>Sarcopenia, the age-related loss of muscle mass and function, poses a significant health burden in aging societies. Although mitochondrial dysfunction is a recognized driver, the upstream molecular regulators remain poorly defined. Here, we identify the mitochondrial translocator protein (TSPO) as a novel negative regulator of myogenesis that is consistently upregulated in aged and sarcopenic muscle. Using gain- and loss-of-function approaches in C2C12 myoblasts, we show that TSPO overexpression disrupts mitochondrial homeostasis, impairs proliferation and differentiation, while TSPO knockdown produces opposite effects-establishing TSPO as a critical modulator of myogenic capacity. Mechanistically, TSPO suppresses the Wnt/β-catenin pathway, and this effect is partially mediated by ROS accumulation. Importantly, in vivo AAV9-mediated TSPO knockdown in aged mice not only restores mitochondrial integrity but also significantly improves muscle mass, strength, and exercise performance. Collectively, our findings uncover a TSPO-Wnt/β-catenin axis that links mitochondrial dysfunction to impaired muscle regeneration in aging. Targeting TSPO may offer a dual-action therapeutic strategy to combat sarcopenia by simultaneously enhancing mitochondrial bioenergetics and reactivating pro-myogenic signaling.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148145823","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":"Exercise-induced changes in physical performance and circulating acyl-CoA binding protein/diazepam binding inhibitor (ACBP/DBI) in older adults with and without HIV.","authors":"Matilde Sánchez-Conde, Léa Montégut, Laura Martín-Pedraza, Isabelle Martins, Laura Luna, Marta Martínez, Pablo Ryan, Carlos López-Otín, Guido Kroemer, Fátima Brañas","doi":"10.1093/gerona/glag136","DOIUrl":"https://doi.org/10.1093/gerona/glag136","url":null,"abstract":"<p><p>Acyl-CoA binding protein (ACBP) is a tissue stress hormone with pro-senescent activity. Exercise promotes healthy ageing, but its relationship with circulating ACBP/DBI levels in older adults is unknown. We assessed the association between exercise-induced functional changes and circulating ACBP/DBI levels in older adults with and without HIV. MOVIhNG is a prospective, longitudinal, multicentre controlled study including sedentary adults aged 50 years or older, with and without HIV. Participants undertook a personalised multicomponent exercise programme comprising strength, aerobic endurance, balance, and flexibility training. Assessments were performed at baseline and after 12, 24, and 48 weeks. Circulating ACBP/DBI levels were measured by ELISA. Physical performance was assessed using the Short Physical Performance Battery (SPPB), the chair stand test (lower-body strength); the biceps curl test (upper-body strength), and the 2-minute step test (aerobic endurance) Associations were analysed using generalized estimating equations adjusted for sex and body-mass index. Sixty participants were included (40 with HIV and 20 without HIV; median age 56·5 years). At 12 weeks, changes in circulating ACBP/DBI were significantly correlated with improvements in upper-body strength and aerobic endurance. Over 48 weeks, increases in aerobic endurance and SPPB scores were independently associated with significant reductions in circulating ACBP/DBI levels. Each one-point increase in SPPB score was associated with a 203 ng/mL decrease in plasma ACBP/DBI. HIV status did not influence overall ACBP/DBI trajectories across follow-up. Exercise-induced improvements in physical performance were associated with reduced circulating ACBP/DBI levels across follow-up in older adults, irrespective of HIV status.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148019774","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":"Monocyte epigenetic age acceleration is linked to non-somatic depressive symptoms in women with and without HIV.","authors":"Nicole Beaulieu Perez, Ke Xu, Yanxun Xu, Lang Lang, Kathryn Anastos, Maria L Alcaide, Mardge Cohen, Sadeep Shrestha, Andrew Edmonds, Jacquelyn Meyers, Seble Kassaye, Igho Ofotokun, Gypsyamber D'Souza, Bradley Aouizerat, Leah H Rubin","doi":"10.1093/gerona/glag083","DOIUrl":"10.1093/gerona/glag083","url":null,"abstract":"<p><p>Depression disproportionately affects women living with HIV, yet symptom heterogeneity and the lack of observable biomarkers can impede detection. Accelerated aging of monocytes-key innate immune cells-may contribute to depression, particularly in this population. A DNA methylation clock, MonoDNAmAge, estimates monocyte biological age and has shown evidence of epigenetic age acceleration (EAA) in women with HIV. Here, we examine MonoDNAmAge as a biomarker of depression in women with and without HIV, differentiating non-somatic from somatic symptom domains. DNA methylation data and Center for Epidemiologic Studies Depression Scale (CES-D) scores were available from 440 Women's Interagency HIV Study participants. Two biological age estimates (HorvathDNAmAge and MonoDNAmAge) were calculated and orthogonalized with chronological age. In the total sample and subsamples stratified by HIV status, we used multiple linear regression to assess how EAAMono and EAAHorvath were associated with depressive symptoms. Standardized β coefficients are reported. The sample included 261 women with HIV (mean chronological age = 43.7 (8.9) years; 38% Black; 48% Hispanic) and 179 women without HIV (mean chronological age = 39.5 (10.0) years; 31% Black; 49% Hispanic). In the overall sample, EAAMono was associated with the non-somatic depressive symptom domain (β = 0.125, p = .018), and anhedonia specifically (β = 0.354, p = .007), adjusting for HIV, race, and ethnicity. This pattern persisted in the subsample with HIV (β = 0.112, p = .085). EAAHorvath was not associated with depression severity or symptom domains. Monocyte aging may represent a sensitive biomarker of non-somatic depression symptoms in women with HIV. The dynamics of monocyte aging and depression warrant further study to clarify mechanistic links.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13180751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147517927","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":"A pragmatic three-component clinical score for cognitive risk stratification in older adults with multimorbidity and frailty.","authors":"Nusrat E Mozid, Imran Hossain Monju, Shakila Sharmin, Sanjana Binte Ahmed","doi":"10.1093/gerona/glag117","DOIUrl":"10.1093/gerona/glag117","url":null,"abstract":"<p><strong>Background: </strong>Simple, scalable clinical tools are needed to identify older adults with cognitive impairment in low-resource settings, yet whether parsimonious approaches can match complex phenotyping methods remains unclear. This study developed a three-component clinical score and compared its discriminative performance with latent class analysis (LCA)-derived multimorbidity phenotypes.</p><p><strong>Methods: </strong>This cross-sectional study included 504 Bangladeshi community-dwelling adults aged ≥65 years with at least one chronic disease. Frailty was assessed using the Fried phenotype, and multimorbidity was self-reported and coded using International Classification of Diseases, 10th Revision. An additive score (0-5 points) incorporating age ≥80 years, ≥3 chronic conditions, and frailty classified participants into low (0-1), moderate (2-3), or high (4-5) risk. Outcomes included global cognition and cognitive impairment (Mini-Mental State Examination [MMSE] < 25).</p><p><strong>Results: </strong>The three-component score showed acceptable discrimination for cognitive impairment (area under the curve [AUC] = 0.72) and explained 33% of MMSE variance. LCA-derived phenotypes demonstrated poor discrimination (AUC = 0.44; difference = 0.28, p < .001). A monotonic gradient was observed across risk categories, impairment prevalence increased across risk categories (59%, 83%, and 96%), corresponding to a 12.8-point MMSE difference across the score range. A frailty-augmented LCA (in which frailty was added to the original disease-only LCA) combined with age yielded a modestly higher AUC (0.764), though at substantially greater analytical complexity.</p><p><strong>Conclusions: </strong>A parsimonious clinical score combining age, multimorbidity, and frailty demonstrated acceptable cross-sectional discrimination for prevalent cognitive impairment and substantially outperformed disease-only multimorbidity phenotyping. Subject to prospective validation, this pragmatic tool may support case-finding and cognitive risk stratification in resource-limited settings.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848417","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":"Exploring mitochondrial genetic features in intervertebral disc degeneration through multi-omics integration analyses.","authors":"Fangxing Xu, Chao Wang, Meng Sun, Shuai Shi, Xuyao Wang, Donghui Liu, Lianhao Yu, Chunyang Xi, Pengyu Kong","doi":"10.1093/gerona/glag121","DOIUrl":"10.1093/gerona/glag121","url":null,"abstract":"<p><p>The mitochondrial genetic basis of intervertebral disc degeneration (IVDD) remains incompletely understood. This study employed multi-omics Mendelian randomization (MR) analysis to investigate the potential mitochondrial-related genetic mechanisms underlying IVDD. Using two-sample MR, we integrated and analyzed multi-omics quantitative trait loci, encompassing methylation, expression, protein abundance, and mitochondrial DNA, from genome-wide association studies (GWAS). Genetic associations with IVDD were obtained from the FinnGen study for discovery and the GWAS Catalog database for validation, with Steiger filtering and co-localization analysis further performed to strengthen causal inference. Additionally, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and drug prediction analyses were comprehensively employed to identify potential therapeutic targets. Our multi-omics evidence identified 23 genes, among which 5 genes (glycine amidinotransferase [GATM], SLC25A13, acyl-CoA dehydrogenase short [ACADS], TSFM, and ATP23) showed tier 1 evidence for IVDD, with GATM demonstrating the strongest support. MR analysis revealed that a higher level of GATM was associated with a reduced risk of IVDD (odds ratio: 0.934, 95% confidence interval, 0.887-0.983). Furthermore, 15 drugs targeting GATM were identified, with HYDRONIDONE completing molecular docking. Through the integration of multi-omics data, we identified 5 promising therapeutic targets for IVDD, with GATM exhibiting the most consistent multi-omics signal, and discovered 15 drugs targeting GATM and 11 drugs targeting ACADS.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147877159","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}