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

{"title":"Differences in blood levels of neuroligin-derived peptides in a cohort for early detection of Alzheimer's disease.","authors":"Milton G F Fernandes, Maxime Pinard, Esen Sokullu, Cyntia Tremblay, Jean-François Gagnon, Frédéric Calon, Benoit Coulombe, Jonathan Brouillette","doi":"10.1093/gerona/glag009","DOIUrl":"10.1093/gerona/glag009","url":null,"abstract":"<p><p>Alzheimer's disease (AD) develops gradually, with significant neurodegeneration already present by the time clinical symptoms emerge. Since synapses are affected early in the disease, synaptic proteins are being investigated as potential markers of the prodromal stage. Using data and plasma samples provided by the Consortium for the early identification of Alzheimer's disease-Quebec, we analyzed plasma levels of neuroligin (NLGN)-derived peptides in cognitively normal (CN) individuals and cognitively impaired (CI) individuals, including those with amnestic mild cognitive impairment and early-stage AD. Plasma levels of NLGN-derived peptides were assessed by quantifying tryptic peptides using liquid chromatography coupled with tandem mass spectrometry. Our findings show that levels of specific NLGN peptides were significantly elevated in CI compared to CN individuals. Receiver operating characteristic curve analysis revealed that some NLGN peptides could distinguish CI individuals. Furthermore, analysis based on mini-mental state examination scores revealed that specific plasma phosphorylated tau peptides were significantly and positively correlated with selected NLGN-derived peptides in more advanced stages of cognitive decline. These results support further investigation into synaptic NLGN-derived peptides in the blood as promising tools for monitoring the earliest stages of AD.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13049705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146121583","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":"Comment on \"exploring the relationship between pain, cognition, and chronic conditions: insights from the HAALSI study in rural South Africa\".","authors":"Cansu Atbas, Mehmet Ilkin Naharci","doi":"10.1093/gerona/glag038","DOIUrl":"https://doi.org/10.1093/gerona/glag038","url":null,"abstract":"","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":"81 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147464342","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":"Associations of physical frailty with risk of incident cardiovascular disease by mediation of plasma metabolome changes.","authors":"Guangbin Sun, Lan Yu, Nayili Mahemuti, Ao Sun, Dongfang Zhang, Yinyue Liu, Rui Xi, Qiang Zhang, Xumei Zhang, Xiaolong Xing, Xueli Yang","doi":"10.1093/gerona/glag035","DOIUrl":"10.1093/gerona/glag035","url":null,"abstract":"<p><strong>Background: </strong>Frailty has been increasingly recognized as a significant contributor to adverse cardiovascular outcomes. However, the metabolic mechanisms underlying this relationship remain unclear. This study aimed to identify metabolomic signatures of frailty and their mediating roles in cardiovascular disease (CVD) risk.</p><p><strong>Methods: </strong>Using data from 95 770 UK Biobank participants, we applied elastic net regularized regression to construct a frailty-related metabolomic signature score comprising 43 plasma metabolites across lipids, amino acids, fatty acids, and energy metabolism. Cox proportional hazards models were used to assess the association between this metabolomic signatures score and incident CVD, coronary heart disease (CHD), and stroke over a median follow-up of 13.81 years. Mediation analysis under a counterfactual framework was conducted to quantify the extent to which the metabolomic signatures mediated the frailty-CVD association.</p><p><strong>Results: </strong>High metabolomic signature scores were significantly associated with increased risks of CVD (hazard ratio [HR] = 1.44; 95% confidence interval [CI]: 1.36-1.53), CHD (HR = 1.50; 95% CI: 1.41-1.61), and stroke (HR = 1.45; 95% CI: 1.37-1.54). Mediation analysis indicated that the metabolomic signature accounted for 14.9% of the association between frailty and overall CVD, 16.0% for CHD, and 16.9% for stroke. Pathway enrichment analysis revealed 7 metabolic pathways significantly enriched in frailty, with the primary associations implicating carbohydrate and amino acid metabolism.</p><p><strong>Conclusions: </strong>This study highlights a distinct frailty-related metabolic profile that independently predicts cardiovascular risk and partially mediates the frailty-CVD association. These findings underscore the value of metabolomic profiling in guiding early detection and prevention strategies for frailty-related cardiovascular outcomes.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146204486","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":"Leveraging precision medicine analytics to optimize inflammation reduction and enhance physical function in older adults.","authors":"Sonum D Tharwani, David H Lynch, Dominic E Boccaccio, Hillary Spangler, Daiqi Gao, Amanda E Nelson, Donglin Zeng, Dakota Batchek, John A Batsis","doi":"10.1093/gerona/glag053","DOIUrl":"10.1093/gerona/glag053","url":null,"abstract":"<p><strong>Background: </strong>Chronic inflammation in older adults is a key contributor to functional decline and mortality. Although anti-inflammatory medications have shown limited success in improving physical function, emerging targeted approaches offer new promise. We applied machine learning to identify clusters of older adults with shared patterns of inflammatory and cardiometabolic dysregulation and evaluated their responses to specific interventions.</p><p><strong>Methods: </strong>We conducted a secondary analysis of the Enabling Reduction of low-grade Inflammation in Seniors (ENRGISE) multicenter, double-blind, placebo-controlled, factorial trial. This trial assessed the effects of losartan, omega-3, combination therapy, or placebo on interleukin-6 (IL-6) levels and 400-m walking speed. Key variables were selected using least absolute shrinkage and selection operator (LASSO), followed by linear regression to identify those significantly affecting the outcome slope. The optimal intervention was defined as the one that maximized the estimated slope improvement.</p><p><strong>Results: </strong>We included 287 participants (47.4% female; mean age 77.6 ± 5.4 years) with a baseline IL-6 of 4.81 pg/mL. If all participants had received the recommended interventions, the estimated mean IL-6 slope would be -0.70 pg/mL/year (95% CI, -3.71, 1.41), compared to -0.51 pg/mL/year (-1.47, 0.35) among those randomized. The estimated improvement in walking speed was +0.0017 m/s/year (-0.0336, 0.0407) for the recommended interventions versus +0.0015 m/s/year (-0.0145, 0.0154) observed in the trial. For grip strength, the slope was -1.02 kg/year (-2.63, 0.57) for the recommended group and -1.02 kg/year (-1.79, -0.45) for the trial group.</p><p><strong>Conclusion: </strong>Although results were not significant, our findings suggest that tailored interventions based on individuals' unique profiles may yield more favorable effects compared to non-tailored approaches. However, further powered studies should continue to explore precision medicine analytics and their potential to help identify more effective and personalized interventions.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146260545","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":"Oxidative stress biomarkers as predictors of aging and age-related diseases.","authors":"Yogesh Kumar, Anuja Pant, Somu Yadav, Pawan Kumar Maurya","doi":"10.1093/gerona/glag056","DOIUrl":"10.1093/gerona/glag056","url":null,"abstract":"<p><p>Oxidative stress (OS) is a major feature of aging and is first brought on when the generation of Reactive oxygen species (ROS) surpasses the capacity of antioxidant defenses to neutralize them. Long-term exposure to ROS gradually damages vital biomolecules, resulting in the development of measurable biomarkers that indicate the degree of OS. Some forms of protein oxidation that impair enzymatic activity and interfere with cellular signaling are carbonyl compounds and advanced oxidation protein products. DNA is susceptible to OS, which can cause lesions like 8-hydroxy-2-deoxyguanosine, which indicates genomic instability and leads to cellular senescence and reduced function. Increased levels of lipid peroxidation byproducts, such as Malondialdehyde, 4-hydroxynonenal, and isoprostanes, indicate disturbed cellular balance and compromised membrane integrity. Additional information about the redox state can be found in antioxidant defenses. While important enzymatic antioxidants like glutathione peroxidase, catalase, and superoxide dismutase frequently show altered activity as one ages, indicating a reduced ability to counteract ROS, non-enzymatic antioxidants like glutathione, vitamins C and E, uric acid, bilirubin, and beta carotene provide extra defense but diminish with age. Combined, these biomarkers show how oxidative damage accumulates gradually and how the body's cellular defenses progressively deteriorate. By mapping their trajectories, we can better understand the biology of aging and develop targeted interventions and early detection tools to promote healthy aging. In this review, we summarized various OS biomarkers that help in the prediction of aging and age-related diseases.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147278166","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":"Particulate air pollution and post-discharge recovery among older adults hospitalized for heart failure in the United States.","authors":"Tong Wen, Jingwen Hu, Michelle Shardell, Rozalina McCoy, Shuo Chen, Kathleen Ryan, Jason Falvey, Chixiang Chen","doi":"10.1093/gerona/glag028","DOIUrl":"10.1093/gerona/glag028","url":null,"abstract":"<p><strong>Background: </strong>The impact of exposure to fine particulate matter (PM2.5) on post-discharge recovery in older adults already hospitalized for heart failure remains unclear. We evaluated associations between exposure to PM2.5 and days spent at home (DAH) as well as mortality in a nationwide representative sample of U.S. adults aged 65 years and older.</p><p><strong>Methods: </strong>Data from 66 854 Medicare Fee-for-service beneficiaries with heart failure hospitalization (2017-2019) were linked with validated, model-derived mean PM2.5 concentrations at Zip Code Tabulation Areas level during the month of hospital admission. Post-discharge 180-day DAH was defined as days alive minus days spent in inpatient hospitals, hospital observation units, nursing facilities, or emergency departments. All-cause mortality was assessed as time from hospital discharge to death within 180 days. Quantile regression and Cox proportional regression models, adjusted for covariates, were used to quantify associations.</p><p><strong>Results: </strong>Exposure to the highest quartile PM2.5 level (>8.61 µg/m3) was associated with 5.05 fewer DAH (95% CI: -8.61, -1.48; p = .006) after discharge at the 20th percentile of DAH, compared with those exposed to the lowest PM2.5 quartile (≤5.90 µg/m3). Exposure to the highest quartile PM2.5 levels was also associated with higher risk of all-cause mortality within 180 days after hospitalization as compared to the lowest PM2.5 quartile (hazard ratio = 1.05, 95% CI: 1.004-1.10, p = .033).</p><p><strong>Conclusions: </strong>Particulate air pollution may negatively impact recovery more strongly at the lower tail of recovery than at the median or higher tail, highlighting the need for targeted intervention strategies to protect the most vulnerable patients.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13016969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146127690","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":"Social and clinical frailty indices in aging mice: a comparative analysis of longitudinal and cross-sectional designs.","authors":"Maria Razzoli, Charles W Collinge, Monica Luciana, Alessandro Bartolomucci","doi":"10.1093/gerona/glag045","DOIUrl":"10.1093/gerona/glag045","url":null,"abstract":"<p><p>Aging is a heterogeneous phenomenon provoked by biological processes that still need to be fully understood. Frailty is a relevant outcome of aging reflecting biological decline that can be quantified through indices measuring the accumulation of functional deficits. Age-related declines may occur across multiple domains of functioning, and longitudinal study designs may better characterize decline within aging individuals. Thus, it is imperative to characterize how frailty indices that capture different functional domains associate with one another over the natural lifespan and across study designs. Here, the clinical frailty index (CFI) and the mouse social frailty index (mSFI) were applied to male and female mice both longitudinally and cross-sectionally over the lifespan. An overall similar association with aging was apparent: within each cohort, both CFI and mSFI were strongly positively associated with age. The utility of the CFI and mSFI as age predictors within the longitudinal study was confirmed. Critically, a model developed within the longitudinal study based on CFI scores, mSFI scores, and sex was able to predict age better than alternative models using only one of the indices. This result suggests that the CFI and the mSFI capture intrinsically different elements of deficit accumulation with age. The same model also showed a good performance in predicting the age of mice in the cross-sectional study. Overall, these results demonstrate that the information captured by both frailty indices is relevant to aging, relationships between indices vary across study design, and both frailty domains are needed to produce better age predictions.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146204351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The relative effects of different exercise modes on physical and metabolic health in older adults: a network meta-analysis.","authors":"Jiuchen Yuan, Fanghui Li, Shusheng Shi, Zhijian Wu","doi":"10.1093/gerona/glag030","DOIUrl":"10.1093/gerona/glag030","url":null,"abstract":"<p><p>Multiple exercise modalities are recommended for older adults, yet their comparative effectiveness remains uncertain. We conducted a Bayesian network meta-analysis of randomized trials to compare common exercise modes on cardiorespiratory fitness and metabolic health in adults aged ≥55 years. Trials randomized participants to high-intensity interval training (HIIT), aerobic training (AT), resistance training (RT), combined aerobic-resistance training (CART), or non-exercise control. The primary outcome was maximal/peak oxygen uptake (VO2max/VO2peak). Secondary outcomes included BMI, body fat percentage, fat-free mass, systolic/diastolic blood pressure, and blood lipids. We fitted random-effects Bayesian network meta-analysis models and summarized ranking probabilities using the surface under the cumulative ranking curve. No exercise modality showed a clear advantage for VO2max/VO2peak; credible intervals were wide for most between-modality comparisons. Versus control, RT increased fat-free mass, CART reduced body fat percentage and systolic blood pressure, and HIIT reduced BMI and triglycerides. For total cholesterol, LDL-C, HDL-C, and diastolic blood pressure, credible intervals generally included the null. Heterogeneity was moderate, and formal inconsistency assessment was limited by sparse networks. Current evidence does not identify a single \"best\" exercise modality for improving VO2max/VO2peak in older adults. Modality selection may be better guided by the primary goal (eg, RT for lean mass, CART for adiposity and systolic blood pressure, HIIT for BMI and triglycerides), while considering feasibility and safety. Larger, well-reported head-to-head trials are needed to strengthen comparative estimates.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146168571","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":"Are aging clocks based on routine clinical indicators trustworthy and applicable? A systematic review and critical appraisal.","authors":"Jiajia Zhang, Jie Hu, Yinyan Gao, Zhilin Pang, Long Mo, Irene X Y Wu","doi":"10.1093/gerona/glag032","DOIUrl":"10.1093/gerona/glag032","url":null,"abstract":"<p><p>Aging clocks based on routine clinical indicators have emerged as a cost-effective tool for assessing biological age. This systematic review aims to summarize the characteristics and critically appraise these available aging clocks. Studies that developed aging clocks for adults (≥18 years) based on routine clinical indicators were retrieved from six databases (PubMed, EMBASE, Web of Science, CNKI, Wanfang Data, and Sinomed) up to June 18, 2024. The PROBAST + AI tool was used to assess the methodological quality, risk of bias, and applicability of included aging clocks. All the results were narratively summarized. Fifty-nine studies involving 81 aging clocks were included, of which 71 (87.7%) were developed using single-country datasets predominantly from China, the United States, Korea, and the United Kingdom. Notably, 31 aging clocks (38.3%) were developed with neither internal nor external validation. The majority of aging clocks were rated as having high concern regarding quality and high risk of bias, even including those published in high-impact journals. Only three aging clocks (3.7%) from two studies were rated as having low concern regarding quality and applicability during development, and two of these (4.0%) from one study further demonstrated low risk of bias and low concern for applicability during model evaluation. Future research should prioritize validating the promising aging clocks in target populations rather than developing new ones, adhere to the PROBAST + AI and TRIPOD + AI guidelines for methodological rigor and transparent reporting, and provide reproducible and user-friendly model codes and tools.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146168573","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":"Benchmarking weighted estimates of social determinants of Health in the National Health and Aging Trends Study (NHATS).","authors":"Thomas M Gill, Linda Leo-Summers, Jingchen Liang, Robert D Becher, Amy J H Kind, Emma X Zang","doi":"10.1093/gerona/glag037","DOIUrl":"10.1093/gerona/glag037","url":null,"abstract":"","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12928736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146204493","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}