BACKGROUNDAssessment of frailty has become common in clinical settings to risk-stratify older adults. Understanding how to use repeated measurements answers important questions both for the clinical use of serial assessments and understanding frailty trajectories.METHODSUsing 2012-16 Health and Retirement Study data, we calculated six summary measures of assessments of frailty index (FI, 3 assessments) and Fried Frailty Phenotype (FFP, 2 assessments): most recent value, maximum, minimum, mean, standard deviation (SD), and delta. We assessed the association of scaled values with mortality and institutionalization between 2016 and 2018, and three measures of epigenetic aging collected in 2016 using Cox, logistic, and linear regression respectively with adjustment for age, sex, and smoking. We then used LASSO regression to determine which summary measures were most often retained.RESULTS14,451 and 2,196 individuals had complete data for FI and FFP respectively. The maximum and most recent frailty values had the strongest associations with the outcomes considered, while those of SD and delta were weakest. In LASSO regressions, the maximum and most recent values were most commonly retained (12-13 of 20 regressions), followed by SD (7), mean (6), and minimum and delta (1 each).CONCLUSIONSThese findings show that maximum and most recent values of frailty tend to be most strongly associated with mortality. For clinicians, this means that the most recent assessment may be sufficient for many purposes and if historical data are unavailable.FUNDINGNational Institute on Aging; Office of Research and Development Department of Veterans Affairs).
背景：虚弱评估在临床环境中对老年人进行风险分层已经变得很常见。了解如何使用重复测量回答了临床使用系列评估和了解脆弱轨迹的重要问题。方法利用2012- 2016年健康与退休研究数据，我们计算了衰弱指数（FI， 3个评估）和Fried衰弱表型（FFP， 2个评估）的6个综合评估指标：最近值、最大值、最小值、平均值、标准差（SD）和delta。我们评估了2016年至2018年间量表值与死亡率和机构化的关系，并分别使用Cox、logistic和线性回归评估了2016年收集的三种表观遗传衰老指标，并调整了年龄、性别和吸烟情况。然后我们使用LASSO回归来确定哪些汇总度量最常被保留。结果FI和FFP数据完整者分别为14451例和2196例。最大和最近的脆弱值与考虑的结果有最强的关联，而SD和delta的关联最弱。在LASSO回归中，最大值和最近的值最常被保留（20个回归中的12-13个），其次是SD (7), mean (6)， minimum和delta（各1）。结论：这些发现表明，最大和最近的虚弱值与死亡率的关系最为密切。对于临床医生来说，这意味着如果没有历史数据，最新的评估可能对许多目的来说都是足够的。美国老龄研究所；退伍军人事务部研究与发展办公室)。
{"title":"Associations of Summary Measures of Longitudinal Frailty Assessments with Health Outcomes.","authors":"Benjamin Seligman,Dae Hyun Kim,Ariela Orkaby","doi":"10.1093/gerona/glaf161","DOIUrl":"https://doi.org/10.1093/gerona/glaf161","url":null,"abstract":"BACKGROUNDAssessment of frailty has become common in clinical settings to risk-stratify older adults. Understanding how to use repeated measurements answers important questions both for the clinical use of serial assessments and understanding frailty trajectories.METHODSUsing 2012-16 Health and Retirement Study data, we calculated six summary measures of assessments of frailty index (FI, 3 assessments) and Fried Frailty Phenotype (FFP, 2 assessments): most recent value, maximum, minimum, mean, standard deviation (SD), and delta. We assessed the association of scaled values with mortality and institutionalization between 2016 and 2018, and three measures of epigenetic aging collected in 2016 using Cox, logistic, and linear regression respectively with adjustment for age, sex, and smoking. We then used LASSO regression to determine which summary measures were most often retained.RESULTS14,451 and 2,196 individuals had complete data for FI and FFP respectively. The maximum and most recent frailty values had the strongest associations with the outcomes considered, while those of SD and delta were weakest. In LASSO regressions, the maximum and most recent values were most commonly retained (12-13 of 20 regressions), followed by SD (7), mean (6), and minimum and delta (1 each).CONCLUSIONSThese findings show that maximum and most recent values of frailty tend to be most strongly associated with mortality. For clinicians, this means that the most recent assessment may be sufficient for many purposes and if historical data are unavailable.FUNDINGNational Institute on Aging; Office of Research and Development Department of Veterans Affairs).","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140418","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}
Helen C S Meier,Eric T Klopack,Mateo P Farnia,Belinda Hernandez,Colter Mitchell,Jessica D Faul,Cathal McCrory,Rose Anne Kenny,Eileen M Crimmins
Chronic low-grade systemic inflammation is a risk factor for chronic diseases and mortality and is an important biomarker in health research. DNA methylation (DNAm) surrogate biomarkers are valuable exposure, risk factor and health outcome predictors in studies where the measures cannot be measured directly and often perform as well or better than direct measure. We generated a DNAm surrogate biomarker for chronic, systemic inflammation from a systemic inflammation latent variable of seven inflammatory markers and evaluated its performance relative to measured inflammatory biomarkers in predicting several age-associated outcomes of interest, including mortality, activities of daily living and multimorbidity in the Health and Retirement Study (HRS). The DNAm surrogate, Inflammation Latent Variable Methylation Surrogate (InfLaMeS), correlated with seven individual inflammation markers (r= -0.2-0.6) and had similar or stronger associations with multimorbidity, disability, and 4-year mortality in HRS compared to the systemic inflammation latent variable measure when predicting multimorbidity, disability, and 4-year mortality in HRS. Findings were validated in an external cohort, The Irish Longitudinal Study of Ageing. These results suggest that InfLaMeS provides a robust alternative to measured blood-chemistry measures of inflammation with broad research applicability in instances where values of inflammatory markers are not measured but DNAm data is available.
{"title":"A novel DNA methylation-based surrogate biomarker for chronic systemic inflammation (InfLaMeS).","authors":"Helen C S Meier,Eric T Klopack,Mateo P Farnia,Belinda Hernandez,Colter Mitchell,Jessica D Faul,Cathal McCrory,Rose Anne Kenny,Eileen M Crimmins","doi":"10.1093/gerona/glaf202","DOIUrl":"https://doi.org/10.1093/gerona/glaf202","url":null,"abstract":"Chronic low-grade systemic inflammation is a risk factor for chronic diseases and mortality and is an important biomarker in health research. DNA methylation (DNAm) surrogate biomarkers are valuable exposure, risk factor and health outcome predictors in studies where the measures cannot be measured directly and often perform as well or better than direct measure. We generated a DNAm surrogate biomarker for chronic, systemic inflammation from a systemic inflammation latent variable of seven inflammatory markers and evaluated its performance relative to measured inflammatory biomarkers in predicting several age-associated outcomes of interest, including mortality, activities of daily living and multimorbidity in the Health and Retirement Study (HRS). The DNAm surrogate, Inflammation Latent Variable Methylation Surrogate (InfLaMeS), correlated with seven individual inflammation markers (r= -0.2-0.6) and had similar or stronger associations with multimorbidity, disability, and 4-year mortality in HRS compared to the systemic inflammation latent variable measure when predicting multimorbidity, disability, and 4-year mortality in HRS. Findings were validated in an external cohort, The Irish Longitudinal Study of Ageing. These results suggest that InfLaMeS provides a robust alternative to measured blood-chemistry measures of inflammation with broad research applicability in instances where values of inflammatory markers are not measured but DNAm data is available.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127257","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}
Weili Zhang, Nan Tang, Jie Song, Mi Song, Qingqing Su, Xiaojie Fu, Yuan Gao
Background Postoperative delirium (POD) is associated with impaired cognitive function, increased morbidity, and mortality. Early identification of high-risk patients is critical for effective intervention. Methods Data from 2,516 older patients with hip fractures treated at the First Medical Center of the Chinese PLA General Hospital were retrospectively collected. Logistic Regression (LR), Random Forest (RF), Classification and Regression Tree (CART), Support Vector Machine (SVM), and Extreme Gradient Boosting (XGBoost) were used to construct the prediction models. SHapley Additive exPlanation (SHAP) analysis was performed to visualize the optimal model. External validation was conducted on 176 patients from March 2022 to November 2023 to assess the model's clinical applicability. Results The training dataset included 2,516 older patients, of which 367 (14.59%) developed POD. XGBoost demonstrated the best predictive performance (AUC = 0.92; accuracy = 86.4%; sensitivity = 87.7%; specificity = 85.1%; Brier score = 0.15). SHAP analysis ranked PNI (Prognostic Nutritional Index), ASA (American Society of Anesthesiologists classification), and age as the top three predictors. External validation on 176 patients showed the XGBoost model maintained strong performance (AUC = 0.89; accuracy = 83.0%; sensitivity = 95.8%; specificity = 80.9%; Brier score = 0.15). Conclusions An ML-based model was developed and validated to predict postoperative delirium risk in older patients with hip fracture. These findings may help to develop personalized interventions to provide better treatment plans and optimal resource allocation. The interpretable framework can increase the transparency of the model and facilitate understanding the reliability of the predictive model for the physicians.
{"title":"Development and Validation of a Machine Learning-Based Risk Prediction Model for Postoperative Delirium in Older Patients with Hip Fracture","authors":"Weili Zhang, Nan Tang, Jie Song, Mi Song, Qingqing Su, Xiaojie Fu, Yuan Gao","doi":"10.1093/gerona/glaf200","DOIUrl":"https://doi.org/10.1093/gerona/glaf200","url":null,"abstract":"Background Postoperative delirium (POD) is associated with impaired cognitive function, increased morbidity, and mortality. Early identification of high-risk patients is critical for effective intervention. Methods Data from 2,516 older patients with hip fractures treated at the First Medical Center of the Chinese PLA General Hospital were retrospectively collected. Logistic Regression (LR), Random Forest (RF), Classification and Regression Tree (CART), Support Vector Machine (SVM), and Extreme Gradient Boosting (XGBoost) were used to construct the prediction models. SHapley Additive exPlanation (SHAP) analysis was performed to visualize the optimal model. External validation was conducted on 176 patients from March 2022 to November 2023 to assess the model's clinical applicability. Results The training dataset included 2,516 older patients, of which 367 (14.59%) developed POD. XGBoost demonstrated the best predictive performance (AUC = 0.92; accuracy = 86.4%; sensitivity = 87.7%; specificity = 85.1%; Brier score = 0.15). SHAP analysis ranked PNI (Prognostic Nutritional Index), ASA (American Society of Anesthesiologists classification), and age as the top three predictors. External validation on 176 patients showed the XGBoost model maintained strong performance (AUC = 0.89; accuracy = 83.0%; sensitivity = 95.8%; specificity = 80.9%; Brier score = 0.15). Conclusions An ML-based model was developed and validated to predict postoperative delirium risk in older patients with hip fracture. These findings may help to develop personalized interventions to provide better treatment plans and optimal resource allocation. The interpretable framework can increase the transparency of the model and facilitate understanding the reliability of the predictive model for the physicians.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089670","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}
Runjie Li, Wenhua Jiang, Huiyu Tang, Shuyue Luo, Xiaoyan Chen, Qian Chen, Ming Yang
Background Sarcopenia, associated with systemic inflammation, respiratory diseases, and known gut dysbiosis, poses a significant health burden. However, the role of the nasopharyngeal and oropharyngeal (NP/OP) microbiome, a critical respiratory-digestive interface, in its pathogenesis remains unknown. Methods From a cohort of 830 nursing home residents with a sarcopenia prevalence of 61%, we conducted a nested case-control study. Sixty individuals with sarcopenia were propensity-score matched 1:1 with 60 non-sarcopenic controls (N = 120; 50% male). NP/OP swabs underwent full-length 16S rRNA gene sequencing to assess microbial composition and function. Results Individuals with sarcopenia exhibited significantly lower OP microbial α-diversity (Shannon p = 0.016), which remained robust after multivariable adjustment (Shannon p < 0.05). NP diversity was unchanged. Sarcopenia was associated with an NP/OP microbial profile suggesting increased pro-inflammatory potential: enrichment of Moraxella (NP, LDA > 2) and Haemophilus, Lactobacillus amylovorus, Listeriaceae (OP, LDA > 2), alongside depletion of potentially protective taxa (Pasteurellaceae, Alloprevotella tannerae, Prevotella aurantiaca, Eubacterium, Lachnoanaerobaculum) in controls. Specifically, increased Moraxella lincolnii (OR = 1.068, p < 0.05) and decreased Eubacterium (OR = 0.968, p < 0.05) were associated with sarcopenia. Functionally, pathways related to lipopolysaccharide (LPS) biosynthesis and saturated fatty acid metabolism were upregulated in sarcopenia, while short-chain fatty acid (SCFA) and tryptophan metabolism were reduced. Conclusion Oropharyngeal microbial dysbiosis, characterized by lower diversity and a pro-inflammatory signature, is associated with sarcopenia. These findings highlight a potential relationship between the upper respiratory tract microbial environment and sarcopenia, a connection previously underappreciated. Understanding the interplay within the respiratory–gut–muscle axis may offer new perspectives on sarcopenia pathophysiology and its links with respiratory diseases.
骨骼肌减少症与全身性炎症、呼吸系统疾病和已知的肠道生态失调有关，会造成严重的健康负担。然而，鼻咽和口咽（NP/OP）微生物组作为一个关键的呼吸-消化界面，在其发病机制中的作用尚不清楚。方法对830名骨骼肌减少症患病率为61%的养老院居民进行巢式病例对照研究。60例肌肉减少症患者与60例非肌肉减少症对照组（N = 120, 50%为男性）的倾向评分匹配为1:1。NP/OP拭子进行全长16S rRNA基因测序以评估微生物组成和功能。结果肌少症患者OP微生物α-多样性显著降低（Shannon p = 0.016），经多变量调整后仍保持稳定（Shannon p < 0.05）。NP多样性没有变化。骨骼肌减少症与NP/OP微生物谱相关，表明促炎潜力增加：在对照组中，莫拉菌（NP, LDA > 2）和嗜血杆菌、淀粉样乳杆菌、李斯特菌科（OP, LDA > 2）的富集，以及潜在保护类群（巴氏杆菌、单宁异普氏菌、金普氏菌、真细菌、拉克诺厌氧菌）的消耗。具体而言，林肯莫拉菌增加（OR = 1.068, p < 0.05）和真杆菌减少（OR = 0.968, p < 0.05）与肌肉减少症相关。在功能上，与脂多糖（LPS）生物合成和饱和脂肪酸代谢相关的途径在肌肉减少症中上调，而短链脂肪酸（SCFA）和色氨酸代谢减少。结论口咽部微生物生态失调与肌肉减少症有关，其特征为多样性降低和促炎特征。这些发现强调了上呼吸道微生物环境与肌肉减少症之间的潜在关系，这是一种以前未被重视的联系。了解呼吸-肠-肌轴之间的相互作用可能为肌肉减少症的病理生理及其与呼吸系统疾病的联系提供新的视角。
{"title":"Oropharyngeal Microbiome Alterations in Sarcopenia: A Nested Case-Control Study in Older Adults","authors":"Runjie Li, Wenhua Jiang, Huiyu Tang, Shuyue Luo, Xiaoyan Chen, Qian Chen, Ming Yang","doi":"10.1093/gerona/glaf201","DOIUrl":"https://doi.org/10.1093/gerona/glaf201","url":null,"abstract":"Background Sarcopenia, associated with systemic inflammation, respiratory diseases, and known gut dysbiosis, poses a significant health burden. However, the role of the nasopharyngeal and oropharyngeal (NP/OP) microbiome, a critical respiratory-digestive interface, in its pathogenesis remains unknown. Methods From a cohort of 830 nursing home residents with a sarcopenia prevalence of 61%, we conducted a nested case-control study. Sixty individuals with sarcopenia were propensity-score matched 1:1 with 60 non-sarcopenic controls (N = 120; 50% male). NP/OP swabs underwent full-length 16S rRNA gene sequencing to assess microbial composition and function. Results Individuals with sarcopenia exhibited significantly lower OP microbial α-diversity (Shannon p = 0.016), which remained robust after multivariable adjustment (Shannon p &lt; 0.05). NP diversity was unchanged. Sarcopenia was associated with an NP/OP microbial profile suggesting increased pro-inflammatory potential: enrichment of Moraxella (NP, LDA &gt; 2) and Haemophilus, Lactobacillus amylovorus, Listeriaceae (OP, LDA &gt; 2), alongside depletion of potentially protective taxa (Pasteurellaceae, Alloprevotella tannerae, Prevotella aurantiaca, Eubacterium, Lachnoanaerobaculum) in controls. Specifically, increased Moraxella lincolnii (OR = 1.068, p &lt; 0.05) and decreased Eubacterium (OR = 0.968, p &lt; 0.05) were associated with sarcopenia. Functionally, pathways related to lipopolysaccharide (LPS) biosynthesis and saturated fatty acid metabolism were upregulated in sarcopenia, while short-chain fatty acid (SCFA) and tryptophan metabolism were reduced. Conclusion Oropharyngeal microbial dysbiosis, characterized by lower diversity and a pro-inflammatory signature, is associated with sarcopenia. These findings highlight a potential relationship between the upper respiratory tract microbial environment and sarcopenia, a connection previously underappreciated. Understanding the interplay within the respiratory–gut–muscle axis may offer new perspectives on sarcopenia pathophysiology and its links with respiratory diseases.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089671","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}
Sharon E Mitchell,Lucile Heib,Cara L Green,Davina Derous,Catherine Hambly,John R Speakman
Calorie restriction (CR) is the reduction in calorie intake while avoiding malnutrition. CR increases longevity and attenuates the development of many age-related diseases, although some unfavourable responses have been reported. In response to CR, energy is withdrawn from tissues to correct the energy deficit. Changes in tissue mass over short-term, 3 months graded CR (STCR) were complex and while most tissues reduced size, some grew. Employing a graded long-term CR (LTCR) protocol in male C57BL/6J mice, tissue utilisation, digestive efficiency, bone health and motor coordination was investigated. Mice were restricted by 10-40% over 580 days/19 months and sacrificed at 24 months old. Control mice fed ad libitum in the 12hr darkphase only (12AL) were regarded as 0CR. The patterns of tissue weights, digestive efficiency, and bone measurements across the levels of CR were consistent between the STCR and LTCR studies, highlighting shared similarities over both experiments. Notable differences were enhanced utilisation of the reproductive accessory organs which could be linked to a shutdown of the reproductive axis; reduced utilisation of the spleen, changes in the hierarchy of investment in the digestive organs which was not linked to digestive efficiency. The vital organs were protected from utilisation, with preservation of the brain by CR, presumably linked to reduced neurodegeneration and sustained coordination. The favourable effects of LTCR on bone health contradict previous negative reports. Overall, morphological changes determined within 3 months of CR, persisted to 19 months. The pattern of tissue utilisation may be critical to the beneficial effects of CR.
{"title":"Effects of graded calorie restriction: XXII. impact of long-term graded calorie restriction on tissue partitioning, digestive efficiency, bone health and coordination in male C57BL/6J mice.","authors":"Sharon E Mitchell,Lucile Heib,Cara L Green,Davina Derous,Catherine Hambly,John R Speakman","doi":"10.1093/gerona/glaf168","DOIUrl":"https://doi.org/10.1093/gerona/glaf168","url":null,"abstract":"Calorie restriction (CR) is the reduction in calorie intake while avoiding malnutrition. CR increases longevity and attenuates the development of many age-related diseases, although some unfavourable responses have been reported. In response to CR, energy is withdrawn from tissues to correct the energy deficit. Changes in tissue mass over short-term, 3 months graded CR (STCR) were complex and while most tissues reduced size, some grew. Employing a graded long-term CR (LTCR) protocol in male C57BL/6J mice, tissue utilisation, digestive efficiency, bone health and motor coordination was investigated. Mice were restricted by 10-40% over 580 days/19 months and sacrificed at 24 months old. Control mice fed ad libitum in the 12hr darkphase only (12AL) were regarded as 0CR. The patterns of tissue weights, digestive efficiency, and bone measurements across the levels of CR were consistent between the STCR and LTCR studies, highlighting shared similarities over both experiments. Notable differences were enhanced utilisation of the reproductive accessory organs which could be linked to a shutdown of the reproductive axis; reduced utilisation of the spleen, changes in the hierarchy of investment in the digestive organs which was not linked to digestive efficiency. The vital organs were protected from utilisation, with preservation of the brain by CR, presumably linked to reduced neurodegeneration and sustained coordination. The favourable effects of LTCR on bone health contradict previous negative reports. Overall, morphological changes determined within 3 months of CR, persisted to 19 months. The pattern of tissue utilisation may be critical to the beneficial effects of CR.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"39 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089852","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}
Recently, the role of peripheral blood mononuclear cells (PBMCs) in neurodegenerative activities has garnered significant attention, yet the role in Alzheimer's disease (AD) remains unclear. Based on our previous single-cell RNA sequencing (scRNA-seq) datasets of PBMCs from healthy controls and AD patients, we identified differentially expressed genes (DEGs) between healthy individuals and AD patients. These DEGs are involved in pathways related to apoptosis regulation, cognition, synaptic organization, and other AD pathology-associated biological processes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. JUN, CHCHD10, HSPA8, RETN, S100A8, ITGA2B, HBG2, PPBP, and HLA-DQA2 have high correlation with these pathways. To further investigate the role of PBMCs in AD, PBMCs from 9- or 6-month-old wild-type mice (WT) were respectively injected into 9- or 6-month-old AD mice, we found that PBMCs could reduce Aβ plaques and phosphor-tau (p-Tau) deposition, improve cognitive function in AD mice without side effects. Additionally, intersection analysis with AD pathogenic genes, quantitative real-time polymerase chain reaction (qRT-PCR) validation and receiver operating characteristic (ROC) curves demonstrated increased JUN expression in PBMCs of AD patients with higher specificity in the diagnosis of AD, with no significant sex- and age- dependent differences observed in its expression. This study provides a critical theoretical foundation for the clinical application of PBMCs and identifies JUN as a key regulatory gene within PBMCs.
{"title":"Infusion of peripheral blood mononuclear cell alleviates amyloid accumulation and cognitive deficits in Alzheimer's disease.","authors":"Lu-Lu Xue,Ya-Qi Yang,Ruo-Lan Du,Zong-Jin Gan,Yang-Yang Zhao,Wen-Jing Wang,Ning Bi,Qiu-Lin Wang,Ting-Hua Wang,Liu-Lin Xiong","doi":"10.1093/gerona/glaf193","DOIUrl":"https://doi.org/10.1093/gerona/glaf193","url":null,"abstract":"Recently, the role of peripheral blood mononuclear cells (PBMCs) in neurodegenerative activities has garnered significant attention, yet the role in Alzheimer's disease (AD) remains unclear. Based on our previous single-cell RNA sequencing (scRNA-seq) datasets of PBMCs from healthy controls and AD patients, we identified differentially expressed genes (DEGs) between healthy individuals and AD patients. These DEGs are involved in pathways related to apoptosis regulation, cognition, synaptic organization, and other AD pathology-associated biological processes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. JUN, CHCHD10, HSPA8, RETN, S100A8, ITGA2B, HBG2, PPBP, and HLA-DQA2 have high correlation with these pathways. To further investigate the role of PBMCs in AD, PBMCs from 9- or 6-month-old wild-type mice (WT) were respectively injected into 9- or 6-month-old AD mice, we found that PBMCs could reduce Aβ plaques and phosphor-tau (p-Tau) deposition, improve cognitive function in AD mice without side effects. Additionally, intersection analysis with AD pathogenic genes, quantitative real-time polymerase chain reaction (qRT-PCR) validation and receiver operating characteristic (ROC) curves demonstrated increased JUN expression in PBMCs of AD patients with higher specificity in the diagnosis of AD, with no significant sex- and age- dependent differences observed in its expression. This study provides a critical theoretical foundation for the clinical application of PBMCs and identifies JUN as a key regulatory gene within PBMCs.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089859","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}
Concepción-Zavaleta Marcio José,Cabellos Acuña Eduardo,Fuentes-Mendoza Jenyfer,Paz-Ibarra José
{"title":"Beyond Nephrology: FGF-23 as a Predictive Biomarker for Frailty and Adverse Outcomes in Older Adults.","authors":"Concepción-Zavaleta Marcio José,Cabellos Acuña Eduardo,Fuentes-Mendoza Jenyfer,Paz-Ibarra José","doi":"10.1093/gerona/glaf191","DOIUrl":"https://doi.org/10.1093/gerona/glaf191","url":null,"abstract":"","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031787","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}
Racial and ethnic disparities in healthy aging represent an emerging public health crisis that will only grow worse as our population grows older. Healthy lifestyle behaviors are proposed as a key strategy to promote healthy aging. However, the potential of lifestyle interventions to address aging health disparities is uncertain. We analyzed data from 42,625 adult participants (aged 20-85 years) participating in National Health and Nutrition Examination Surveys (NHANES), 1999-2018 to evaluate relationships among healthy lifestyle behaviors and biological aging across White, Black, and Hispanic-identifying groups. We measured healthy lifestyle as adherence to a Mediterranean Diet and level of leisure-time physical activity using established methods. We measured healthy aging using the PhenoAge biological age algorithm applied to blood chemistry data. We tested associations within each race/ethnic identity group and compared associations across groups using regression models with interaction terms. We found that within each race/ethnic identity group, greater adherence to a Mediterranean Diet and higher levels of leisure-time physical activity were associated with younger biological age, independent of demographic and socioeconomic confounders, obesity, and smoking. However, these associations were stronger among White- as compared to non-Hispanic Black- and Hispanic-identifying adults. Results suggest that healthy lifestyle factors are likely to promote healthy aging across the population. However, lifestyle factors along may not be sufficient to completely address race/ethnic disparities in healthy aging. Future studies will need to investigate additional ways to reduce racial and ethnic disparities in healthy aging.
{"title":"Racial/ethnic differences in the association of lifestyle factors with biological aging in NHANES, 1999-2018.","authors":"Talha Arif,Aline Thomas,Daniel W Belsky,Yian Gu","doi":"10.1093/gerona/glaf194","DOIUrl":"https://doi.org/10.1093/gerona/glaf194","url":null,"abstract":"Racial and ethnic disparities in healthy aging represent an emerging public health crisis that will only grow worse as our population grows older. Healthy lifestyle behaviors are proposed as a key strategy to promote healthy aging. However, the potential of lifestyle interventions to address aging health disparities is uncertain. We analyzed data from 42,625 adult participants (aged 20-85 years) participating in National Health and Nutrition Examination Surveys (NHANES), 1999-2018 to evaluate relationships among healthy lifestyle behaviors and biological aging across White, Black, and Hispanic-identifying groups. We measured healthy lifestyle as adherence to a Mediterranean Diet and level of leisure-time physical activity using established methods. We measured healthy aging using the PhenoAge biological age algorithm applied to blood chemistry data. We tested associations within each race/ethnic identity group and compared associations across groups using regression models with interaction terms. We found that within each race/ethnic identity group, greater adherence to a Mediterranean Diet and higher levels of leisure-time physical activity were associated with younger biological age, independent of demographic and socioeconomic confounders, obesity, and smoking. However, these associations were stronger among White- as compared to non-Hispanic Black- and Hispanic-identifying adults. Results suggest that healthy lifestyle factors are likely to promote healthy aging across the population. However, lifestyle factors along may not be sufficient to completely address race/ethnic disparities in healthy aging. Future studies will need to investigate additional ways to reduce racial and ethnic disparities in healthy aging.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"128 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031788","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}
Aung Zaw Zaw Phyo,Sara E Espinoza,Suzanne G Orchard,Rory Wolfe,Anne M Murray,Robyn L Woods,Joanne Ryan
BACKGROUNDGrip strength and gait speed are key markers of physical functional capacity and general health in older people. This study aimed to examine the effect of low-dose aspirin on hand-grip strength and habitual gait speed in relatively healthy older people.METHODSThe ASPREE (ASPirin in Reducing Events in the Elderly) trial randomized 19,114 community-dwelling Australians and U.S. adults aged 70+ years (U.S. minorities ≥65 years) who were free of overt cardiovascular disease, dementia and limitations in activities of daily living to daily 100 mg aspirin versus placebo. Linear mixed models were used to compare the effects of treatment groups on changes in grip strength and gait speed over time, and Cox proportional hazard models were used to compare time to incident grip weakness and gait slowness between aspirin and placebo groups.RESULTSOver a median of 4.7 years, the changes in grip strength (Beta: 0.001; 95% CI: -0.004 to 0.005) and gait speed (Beta: -0.004; 95% CI: -0.010 to 0.001) did not differ significantly between aspirin and placebo groups. Over the study period, 6203 participants experienced incident grip weakness, and 6947 had incident gait slowness. There was no difference in the risk of incident grip weakness (HR: 1.05; 95% CI: 1.00, 1.10) and gait slowness (HR: 1.00; 95% CI: 0.95, 1.05) between individuals randomized to aspirin versus placebo.CONCLUSIONSLow-dose aspirin use in relatively healthy older people did not affect gait speed or grip strength over time or reduce the risk of weakness and slowness.
{"title":"Effect of Aspirin on Grip Strength and Gait Speed in Community-Dwelling Older Adults in the ASPirin in Reducing Events in the Elderly (ASPREE) Study.","authors":"Aung Zaw Zaw Phyo,Sara E Espinoza,Suzanne G Orchard,Rory Wolfe,Anne M Murray,Robyn L Woods,Joanne Ryan","doi":"10.1093/gerona/glaf198","DOIUrl":"https://doi.org/10.1093/gerona/glaf198","url":null,"abstract":"BACKGROUNDGrip strength and gait speed are key markers of physical functional capacity and general health in older people. This study aimed to examine the effect of low-dose aspirin on hand-grip strength and habitual gait speed in relatively healthy older people.METHODSThe ASPREE (ASPirin in Reducing Events in the Elderly) trial randomized 19,114 community-dwelling Australians and U.S. adults aged 70+ years (U.S. minorities ≥65 years) who were free of overt cardiovascular disease, dementia and limitations in activities of daily living to daily 100 mg aspirin versus placebo. Linear mixed models were used to compare the effects of treatment groups on changes in grip strength and gait speed over time, and Cox proportional hazard models were used to compare time to incident grip weakness and gait slowness between aspirin and placebo groups.RESULTSOver a median of 4.7 years, the changes in grip strength (Beta: 0.001; 95% CI: -0.004 to 0.005) and gait speed (Beta: -0.004; 95% CI: -0.010 to 0.001) did not differ significantly between aspirin and placebo groups. Over the study period, 6203 participants experienced incident grip weakness, and 6947 had incident gait slowness. There was no difference in the risk of incident grip weakness (HR: 1.05; 95% CI: 1.00, 1.10) and gait slowness (HR: 1.00; 95% CI: 0.95, 1.05) between individuals randomized to aspirin versus placebo.CONCLUSIONSLow-dose aspirin use in relatively healthy older people did not affect gait speed or grip strength over time or reduce the risk of weakness and slowness.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031786","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}
Ríona Mc Ardle,Lynne Taylor,Silvia Del Din,Lynn Rochester,Ngaire Kerse,Jochen Klenk
BACKGROUNDAmbulatory older residents in long-term care(LTC) have the highest risk of falling. However, the relationship between ambulatory activity (steps per day) and fall risk in LTC is unclear. This study examined whether baseline daily step count, functional capacity and cognitive function predicted falls in LTC residents, and whether functional capacity modified the relationship between step count and fall risk.METHODS276 LTC residents from New Zealand-based Staying UpRight randomised controlled trial were included (age: 84 ± 7 years;61% female). Baseline daily step count was derived from a lumbar-based accelerometer (3,589 ± 2,379steps). Falls rates were calculated from facilities' falls reports (6 ± 18falls). Residents were categorised as Moderate (n = 71) or Low functional capacity (n = 205) based on Short Physical Performance Battery scores. The Montreal Cognitive Assessment assessed cognition (15 ± 6). Quasipoisson generalised linear models explored associations between steps, cognition and functional capacity with falls rates, including interactions between capacity and steps. Relative risk of falling and fall-related injuries were estimated between activity levels.RESULTSKey results showed a significant interaction (p = 0.036) indicating that only the Moderate functional capacity group had a positive association between steps and falls rates. The Moderate group had a ∼23-24% and ∼6% higher relative risk of falls and fall-related injuries respectively with higher activity, while the Low group showed a lower risk of falls (∼2.7-3.9%) and falls-related injuries (2-4%). Cognitive function was not associated with falls.CONCLUSIONSFindings suggest that higher exposure to ambulatory activity is related to greater falls risk but not falls-related injuries only among residents with moderate functional capacity. This stratification should be considered when shaping falls prevention policies.
{"title":"Rethinking the relationship between ambulatory activity and falls in long-term care: Risk versus reward.","authors":"Ríona Mc Ardle,Lynne Taylor,Silvia Del Din,Lynn Rochester,Ngaire Kerse,Jochen Klenk","doi":"10.1093/gerona/glaf197","DOIUrl":"https://doi.org/10.1093/gerona/glaf197","url":null,"abstract":"BACKGROUNDAmbulatory older residents in long-term care(LTC) have the highest risk of falling. However, the relationship between ambulatory activity (steps per day) and fall risk in LTC is unclear. This study examined whether baseline daily step count, functional capacity and cognitive function predicted falls in LTC residents, and whether functional capacity modified the relationship between step count and fall risk.METHODS276 LTC residents from New Zealand-based Staying UpRight randomised controlled trial were included (age: 84 ± 7 years;61% female). Baseline daily step count was derived from a lumbar-based accelerometer (3,589 ± 2,379steps). Falls rates were calculated from facilities' falls reports (6 ± 18falls). Residents were categorised as Moderate (n = 71) or Low functional capacity (n = 205) based on Short Physical Performance Battery scores. The Montreal Cognitive Assessment assessed cognition (15 ± 6). Quasipoisson generalised linear models explored associations between steps, cognition and functional capacity with falls rates, including interactions between capacity and steps. Relative risk of falling and fall-related injuries were estimated between activity levels.RESULTSKey results showed a significant interaction (p = 0.036) indicating that only the Moderate functional capacity group had a positive association between steps and falls rates. The Moderate group had a ∼23-24% and ∼6% higher relative risk of falls and fall-related injuries respectively with higher activity, while the Low group showed a lower risk of falls (∼2.7-3.9%) and falls-related injuries (2-4%). Cognitive function was not associated with falls.CONCLUSIONSFindings suggest that higher exposure to ambulatory activity is related to greater falls risk but not falls-related injuries only among residents with moderate functional capacity. This stratification should be considered when shaping falls prevention policies.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008821","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}
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