Experimental gerontology最新文献

{"title":"Investigating the relationship between sleep disturbances and cortical thickness, brainstem volume, amyloid accumulation, and inflammatory markers in Parkinson's disease patients","authors":"Min Chen ,&nbsp;Gongbing Guo ,&nbsp;Shuangyu Liu ,&nbsp;Jingjing Cai ,&nbsp;Xueying Tong ,&nbsp;Xia Liu ,&nbsp;Yufei Zhang ,&nbsp;Yanhong Chen ,&nbsp;Jiangtao Huo","doi":"10.1016/j.exger.2025.112762","DOIUrl":"10.1016/j.exger.2025.112762","url":null,"abstract":"<div><h3>Background</h3><div>This study aimed to explore the relationship between self-reported sleep disturbances (e.g., insomnia, REM sleep behavior disorder [RBD]) and cortical thickness, brainstem volume, amyloid accumulation, and inflammatory markers in Parkinson's disease (PD) patients.</div></div><div><h3>Methods</h3><div>We conducted a cross-sectional study comparing 100 PD patients (observation group) with 100 age-matched controls. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), and serum levels of amyloid-beta (Aβ1-42), α-synuclein, and inflammatory markers (CRP, TNF-α, IL-1β) were quantified.</div></div><div><h3>Results</h3><div>PD patients exhibited significantly poorer sleep quality (PSQI total score: 2.11 ± 0.27 vs. 0.52 ± 0.02, <em>P</em> &lt; 0.001), reduced parietal cortical thickness (2.68 ± 0.12 mm vs. 3.15 ± 0.18 mm, <em>P</em> = 0.003), and lower brainstem volume (2697.42 ± 147.05 mm³ vs. 3185.16 ± 255.41 mm³, <em>P</em> = 0.007) compared to controls. Biomarker profiling revealed elevated amyloid pathology in PD, with higher serum Aβ1-42 (median [IQR]: 1.98 [1.75–2.22] vs. 1.14 [1.10–1.19], <em>P</em> &lt; 0.001) and α-synuclein (2.03 [1.85–2.22] vs. 1.06 [1.03–1.10], <em>P</em> &lt; 0.001). Proinflammatory markers were markedly increased in PD, including CRP (9.30 [7.85–10.75] vs. 6.30 [5.60–7.10], <em>P</em> = 0.01), TNF-α (372.20 [329.85–414.55] vs. 184.50 [165.20–203.80], <em>P</em> &lt; 0.001), and IL-1β (573.50 [497.15–649.85] vs. 115.40 [101.05–129.75], <em>P</em> &lt; 0.001). Multivariate analysis identified cortical thinning, brainstem atrophy, and IL-1β elevation as independent predictors of sleep disturbances (<em>P</em> &lt; 0.05).</div></div><div><h3>Conclusion</h3><div>These findings highlight the interplay between neuroanatomical changes, amyloid pathology, and systemic inflammation in PD-related sleep dysfunction, suggesting potential therapeutic targets.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"205 ","pages":"Article 112762"},"PeriodicalIF":3.9,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860239","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":"Equating conversion norms for the Mini-Mental State Examination and Montreal Cognitive Assessment in healthy subjects and patients with neurodegenerative disorders","authors":"Sara Bernini ,&nbsp;Elena Ballante ,&nbsp;Marta Picascia ,&nbsp;Marica Barbieri ,&nbsp;Alfredo Costa ,&nbsp;Elena Cavallini ,&nbsp;Cristina Tassorelli ,&nbsp;Tomaso Vecchi ,&nbsp;Sara Bottiroli","doi":"10.1016/j.exger.2025.112756","DOIUrl":"10.1016/j.exger.2025.112756","url":null,"abstract":"<div><h3>Introduction</h3><div>The Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) are globally recognized as validated cognitive screening tests widely used.</div></div><div><h3>Objective/aim</h3><div>The present study attempted to provide conversion tables from the MMSE to the MoCA and vice versa, deriving them from a large population of healthy older adults and a representative clinical sample of subjects with different types of cognitive decline within the spectrum of Alzheimer's (AD) and Parkinson's (PD) diseases.</div></div><div><h3>Methods</h3><div>A total of 1423 Italian participants, including healthy adults (n = 1203), individuals with AD (n = 93), and with PD (n = 127) were assessed using the MMSE and MoCA. Conversion tables were developed using log-linear smoothing equipercentile equating (LSEE). The reliability of the conversion was assessed through the Root Mean Square Error (RMSE) in a train-test approach confirmed in the whole sample.</div></div><div><h3>Results</h3><div>The findings demonstrated that the LSEE method enables the development of conversion tables allowing users to identify the corresponding MoCA score for each MMSE score within the studied groups, and vice versa. The estimation error RMSE was 1.8, 2.9, and 3.2 for the conversion of MoCA from MMSE and 1.2, 2.3, and 2.2 for the conversion of MMSE from MoCA in healthy subjects, AD, and PD, respectively. The reliability of the conversion is higher in healthy subjects and for higher values of MoCA and MMSE.</div></div><div><h3>Conclusion</h3><div>Results report easy-to-use conversion norms for transforming raw MMSE score to MoCA and vice versa, highlighting areas were the conversion has a strong or low reliability depending on the score range.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"205 ","pages":"Article 112756"},"PeriodicalIF":3.9,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860237","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":"Magnesium depletion score in relation to frailty prevalence and mortality in US older adults: Evidence from 1999–2018 NHANES","authors":"Haifeng Jiang ,&nbsp;Wei Tao ,&nbsp;Ting Jia ,&nbsp;Weiwei Liu","doi":"10.1016/j.exger.2025.112757","DOIUrl":"10.1016/j.exger.2025.112757","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to explore the associations between magnesium depletion score (MDS) and frailty prevalence, as well as its prognostic significance for all-cause and cardiovascular mortality among US older adults with frailty.</div></div><div><h3>Methods</h3><div>We analyzed data from older adults participating in the 1999–2018 National Health and Nutrition Examination Survey. The primary exposure was MDS, and the main outcomes were prevalence of frailty as defined by the 49-item accumulation-deficit model and all-cause or cardiovascular mortality in frail participants. The associations between MDS and frailty prevalence or mortality were analyzed using multivariable-adjusted logistic regression and Cox proportional hazards models, respectively.</div></div><div><h3>Results</h3><div>Overall, 13,551 participants (mean age 71.31 years, 45.46 % men, 4464 with frailty) were included. Compared with the MDS = 0 group, the multivariable-adjusted odds ratio and 95 % confidence interval (CI) for frailty were 1.144 (0.899–1.456), 1.702 (1.327–2.183), and 2.661 (2.038–3.475) for the MDS = 1, MDS = 2, and MDS ≥ 3 groups, respectively. A total of 2195 (791 cardiovascular-related) deaths occurred during a median follow-up of 70 months. Compared with the MDS = 0 group, the hazard ratios and 95 % CIs for the MDS = 1, MDS = 2, and MDS ≥ 3 groups were 1.509 (1.146–1.986), 1.988 (1.515–2.611), and 2.751 (2.125–3.562), respectively, for all-cause mortality, and 1.376 (0.843–2.246), 1.933 (1.183–3.160), and 2.872 (1.817–4.541), respectively for cardiovascular mortality.</div></div><div><h3>Conclusions</h3><div>A higher MDS is related to a higher prevalence of frailty and increased risk of all-cause and cardiovascular mortality in US older adults.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"205 ","pages":"Article 112757"},"PeriodicalIF":3.9,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843901","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 role of microRNAs in dexamethasone-induced skeletal muscle atrophy","authors":"Subi Ren ,&nbsp;Jie Chai ,&nbsp;Lijuan Zhang ,&nbsp;JiGang Li ,&nbsp;Xi Long ,&nbsp;Tinghuan Zhang","doi":"10.1016/j.exger.2025.112749","DOIUrl":"10.1016/j.exger.2025.112749","url":null,"abstract":"<div><div>Muscle atrophy is characterized by a decrease in muscle mass, strength, and activity. Recently, it was determined that microRNAs (miRNAs) can regulate muscle atrophy and that dexamethasone (Dex), an allergy and autoimmune disorder treatment that can induce muscle atrophy. Therefore, this study was designed to identify miRNAs expressed in Dex-induced muscle atrophy in mice using small RNA sequencing. A total of 820 miRNAs were identified, with 58 miRNAs expressed explicitly in atrophic muscles. Dex-induced muscle atrophy miRNAs clustered separately from the differential miRNAs in aging, disuse, and cancer-induced muscle atrophy models. The target genes of Dex-induced muscle atrophy miRNAs were independently enriched in inositol phosphate metabolism, hypoxia-inducible factor-1 signaling pathway, <em>etc.</em> Of note, there was a significant increase in the volume of fat cells and adipose weight in the Dex group, suggesting that fat deposition during Dex-induced skeletal muscle atrophy is a unique and typical feature.</div></div><div><h3>Simple summary</h3><div>Dexamethasone (Dex) is a glucocorticoid used to treat allergic and autoimmune diseases, but excessive use can lead to skeletal muscle atrophy. We used dexamethasone (Dex) to build a muscle atrophy model in mice, and obvious changes had taken place in mouse body weight, muscle tissue morphology and related genes. A large number of microRNAs were found to be differentially expressed, and their functions were enriched in pathways related to muscle development. At the same time, we compared the similarities and differences of microRNAs and their functions between Dex induced muscle atrophy model and other muscle atrophy models. Finally, we were surprised to find that Dex induced muscle atrophy is specifically accompanied by the accumulation of body fat.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"205 ","pages":"Article 112749"},"PeriodicalIF":3.9,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143876685","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":"Multimorbidity frailty index and clinical outcomes among 42,989 older heart failure patients directly discharged from emergency departments: A nationwide retrospective cohort study","authors":"Wan-Ju Liao ,&nbsp;Hsi-Yu Lai ,&nbsp;Liang-Yi Lin ,&nbsp;Cheng-Hsueh Wu ,&nbsp;Fei-Yuan Hsiao ,&nbsp;Liang-Kung Chen","doi":"10.1016/j.exger.2025.112754","DOIUrl":"10.1016/j.exger.2025.112754","url":null,"abstract":"<div><h3>Aims</h3><div>Frailty, a common and clinically significant condition in older adults with heart failure (HF), is often overlooked in emergency department (ED) settings. This study aims to evaluate the impact of frailty on clinical outcomes in older adults directly discharged from the ED due to HF.</div></div><div><h3>Methods and results</h3><div>This retrospective cohort study used data from Taiwan's National Health Insurance (NHI) database, identifying older adults (≥65 years) discharged from the ED due to HF between 2017 and 2021. Frailty was assessed using a 38-item multimorbidity frailty index (mFI) derived from ICD-10-CM codes, stratifying patients into fit, mild-to-moderately frail, and severely frail. Outcomes included all-cause mortality, all-cause readmissions, and HF-related readmissions. Cox regression and Fine and Gray models estimated the impact of frailty on these outcomes. Among 42,989 older HF patients (mean age 80.7 ± 8.2 years, 55.5 % female), 57.8 % were frail (46.4 % mild-to-moderately frail and 11.4 % severely frail). Six-month mortality rates were 12.0 % in fit, 16.0 % in mild-to-moderately frail, and 19.4 % in severely frail patients. Readmission rates showed similar patterns. The severely frail group had higher risks of mortality (aHR 1.44, 95 % CI 1.33–1.55), all-cause readmissions (sHR 1.69, 95 % CI 1.62–1.76), and HF-related readmissions (sHR 1.59, 95 % CI 1.48–1.71).</div></div><div><h3>Conclusion</h3><div>Frailty is prevalent among older adults directly discharged from the ED due to HF and significantly elevates risks of mortality and readmissions. These findings highlight the need for frailty assessment in ED settings for older HF patients to optimize care planning, and improve outcomes.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"205 ","pages":"Article 112754"},"PeriodicalIF":3.9,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843902","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":"Sarcopenia index based on serum creatinine and cystatin C is associated with all-cause mortality in patients aged 50 and over with hip fracture","authors":"Longqing Yu ,&nbsp;Fupeng Liu ,&nbsp;Qiuping Zhang ,&nbsp;Wenhua Yan ,&nbsp;Mei Zhang","doi":"10.1016/j.exger.2025.112750","DOIUrl":"10.1016/j.exger.2025.112750","url":null,"abstract":"<div><h3>Background</h3><div>Sarcopenia index (SI), calculated as serum creatinine/cystatin C × 100, has emerged as a potential marker for muscle loss and adverse outcomes. However, its prognostic value in hip fracture patients remains unclear. This study aimed to investigate the association between SI and all-cause mortality in patients aged 50 and over with hip fracture.</div></div><div><h3>Methods</h3><div>This study included patients aged 50 and over with low-energy hip fractures and followed them for at least two years to track the incidence of death. Collect baseline demographic, clinical and biochemical data. Kaplan-Meier and log-rank analyses were performed to compare the mortality between different SI levels. Univariate and multivariate cox regression models were used to evaluate the relationship between SI and all-cause mortality in patients aged 50 and over with hip fracture. Subgroup analysis was carried out to evaluate the influence of potential regulators, and cubic spline curves were limited to check the potential nonlinear relationship between SI and all-cause mortality.</div></div><div><h3>Results</h3><div>A total of 637 patients were enrolled in the study, 62 deaths occurred during follow-up. Non-survivors were significantly older (80.02 ± 9.24 vs 71.05 ± 10.75 years, <em>P</em> &lt; 0.001) and had lower SI values (54.06 ± 11.17 vs 61.51 ± 14.51, P &lt; 0.001) compared to survivors. Kaplan-Meier analysis showed significantly better survival in the high SI group (<em>P</em> = 0.0034). In multivariate analysis, SI remained independently associated with mortality after adjusting for comprehensive covariates (HR = 0.98, 95 % CI: 0.95–0.99, <em>P</em> = 0.018). Restricted cubic spline analysis revealed a nearly linear relationship between SI and the risk of death in patients with hip fractures. In subgroup analysis except in diabetes and BMI ≥ 24, SI was negatively correlated with the second hip fracture.</div></div><div><h3>Conclusions</h3><div>Lower SI values are independently associated with increased all-cause mortality in patients aged 50 and over with hip fracture. SI might serve as a valuable prognostic marker for risk stratification in this population, potentially helping identify high-risk patients who may benefit from more intensive monitoring and intervention.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"204 ","pages":"Article 112750"},"PeriodicalIF":3.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828400","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 frailty with respiratory tract infections: Evidence from cross-sectional analysis and mendelian randomization","authors":"Wei Du,&nbsp;Xi Qiao,&nbsp;Weiai Jia,&nbsp;Chao Li,&nbsp;Huiqun Jia","doi":"10.1016/j.exger.2025.112753","DOIUrl":"10.1016/j.exger.2025.112753","url":null,"abstract":"<div><h3>Background</h3><div>Respiratory tract infections (RTI) remain a challenge to global health, particularly in the frail populations. However, an understanding of the causal relationship between frailty and RTI is limited.</div></div><div><h3>Methods</h3><div>Two complementary approaches were used. First, we conducted a cross-sectional analysis to examine the association between frailty index (FI) and RTI, using data from the NHANES 2013–2014. We then introduced Mendelian randomization (MR) using genome-wide association study summary statistics to determine the causality between frailty index, low grip strength, walking pace, light physical activity, and upper (URTI) or lower RTI (LRTI). The primary method of inverse variance weighting and complementary MR methods were used to verify causality. Sensitivity analysis was conducted to confirm the robustness of the primary results.</div></div><div><h3>Results</h3><div>A total of 2249 participants were enrolled in the cross-sectional study. Weighted multivariable-adjusted logistic regression analysis showed that the frailty index was positively associated with RTI after adjusting for covariates (Continuous FI, odds ratio [OR] = 4.95; 95 % confidence interval [CI], 1.69–14.50, <em>P</em> = 0.004; Categorical FI, OR = 1.51 [95 % CI, 1.11–2.06, <em>P</em> = 0.009]). Restricted cubic spline analysis showed a significant increase in the prevalence of RTI when FI was &gt;0.24. The results of the MR analysis supported a causal relationship between the frailty index and LRTI (OR = 1.939 [95 % CI, 1.180–3.186, <em>P</em> = 0.009]). Sensitivity analysis further confirmed the robustness of these findings.</div></div><div><h3>Conclusion</h3><div>Our study identified a potential association between the FI and RTI at both phenotypic and genetic levels. The results revealed a causal relationship between the FI and LRTI.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"205 ","pages":"Article 112753"},"PeriodicalIF":3.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834165","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":"Sarcopenic obesity is associated with long-term trajectories of physical activity and sedentary behavior","authors":"Aarón Salinas-Rodríguez,&nbsp;Ana Rivera-Almaraz,&nbsp;Betty Manrique-Espinoza","doi":"10.1016/j.exger.2025.112752","DOIUrl":"10.1016/j.exger.2025.112752","url":null,"abstract":"<div><h3>Background</h3><div>Sarcopenia is characterized by decreased muscle mass and strength, and when combined with obesity, it is called sarcopenic obesity (SO). Like sarcopenia, SO is associated with adverse health outcomes This study aimed to investigate the association between SO with the longitudinal, long-term trajectories of physical activity (PA) and sedentary behavior (SB).</div></div><div><h3>Methods</h3><div>Data came from four waves of the WHO Study on Global AGEing and Adult Health (SAGE) in Mexico (2009, 2014, 2017, 2021). A total of 1484 older adults aged 50 years and above were included in the study. PA and SB were determined by using the Global Physical Activity Questionnaire. Sarcopenia was defined according to the criteria of the European Working Group on Sarcopenia in Older People, and obesity according to waist circumference. Growth mixture modeling was used to investigate the longitudinal trajectories of PA and SB.</div></div><div><h3>Results</h3><div>Three longitudinal trajectories of PA and SB were found: low-PA-decreasers, moderate-PA-decreasers, and high-PA-decreasers for PA; and low-maintainers, steep-decreasers, and steep-increasers for SB. Decreased odds of SO were consistently associated with better PA and SB trajectories.</div></div><div><h3>Conclusions</h3><div>The results of this study showed that sustained long-term trajectories of adequate levels of PA and SB are associated with lower rates of SO. The findings of this study support the evidence that regular PA can help reduce the likelihood of developing SO.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"204 ","pages":"Article 112752"},"PeriodicalIF":3.9,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143823886","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":"UBE2N modulates osteoclast differentiation via BTK-PLCγ2-Ca2+ signaling pathway to promote osteoporosis","authors":"Yiqing Chen ,&nbsp;Ruixue Ying ,&nbsp;Liya Ai ,&nbsp;Fang Dai ,&nbsp;Qiu Zhang ,&nbsp;Ping Wang ,&nbsp;Fuhua Chen","doi":"10.1016/j.exger.2025.112751","DOIUrl":"10.1016/j.exger.2025.112751","url":null,"abstract":"<div><div>Osteoporosis is a prevalent public health issue and the underlying mechanism is an imbalance in bone remodeling. Excessive bone resorption caused by upregulation of osteoclast activity is a key factor in the pathogenesis of osteoporosis. Studies have shown that RNA binding protein (RBP) may play an important role in mechanism of OP through interaction with RNA. It has been reported that ubiquitin conjugating enzyme 2 N (UBE2N), as an RBP, is highly expressed in the clinical samples of osteoporotic patients. However, the role and mechanism of action of UBE2N in the regulation of osteoclast differentiation remain unclear. The aim of this study is to evaluate the effects and mechanisms of UBE2N in promoting osteoclastogenesis. In this study, we demonstrated that UBE2N is notably elevated in patients with osteoporosis. Furthermore, our findings revealed that the interference of UBE2N significantly improves osteoporosis of mice, and impedes osteoclast differentiation and bone resorption both in vitro and in vivo. To investigate the molecular mechanisms by which UBE2N influences osteoclast differentiation and bone resorption, we employed RNA sequencing to investigate its downstream related molecules and established that UBE2N regulated the expression of bruton tyrosine kinase (BTK). More importantly, we found that UBE2N may affect osteoclast differentiation and bone resorption by enhancing the expression of the p-BTK gene, which activates the phospholipase Cγ2 (PLCγ2)-Ca²⁺ signaling pathway. Based on these findings, our study highlights the potential of UBE2N as a promising therapeutic target for osteoporosis.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"204 ","pages":"Article 112751"},"PeriodicalIF":3.9,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143821254","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":"Age at menarche and risk of non-alcoholic fatty liver disease: Insights from the NHANES 2017–2020 and Mendelian randomization analyses","authors":"Guifei Si ,&nbsp;Xiaopan Lv ,&nbsp;Yuxin Ge ,&nbsp;Rui Zhang ,&nbsp;Dongxiao Hao ,&nbsp;Xuemei Chen ,&nbsp;Changchun Wang ,&nbsp;Yuquan Li ,&nbsp;Xiuping Li ,&nbsp;Xuemin Yuan","doi":"10.1016/j.exger.2025.112748","DOIUrl":"10.1016/j.exger.2025.112748","url":null,"abstract":"<div><h3>Background</h3><div>This study aimed to explore the causal relationship between age at menarche (AAM) and non-alcoholic fatty liver disease (NAFLD), leveraging data from the 2017–2020 National Health and Nutrition Examination Survey (NHANES) alongside Mendelian randomization (MR) analyses. Notably, this research represents the first attempt to link AAM to NAFLD using genetic methodologies, thereby providing novel insights into the interplay between these two conditions.</div></div><div><h3>Methods</h3><div>Cross-sectional data from 2730 participants were analyzed using logistic regression to evaluate the association between AAM and NAFLD risk. A two-sample MR study was performed to investigate causal relationships, utilizing genetic data from large-scale genome-wide association studies (GWASs). The inverse variance weighted (IVW) method served as the primary MR analysis approach.</div></div><div><h3>Results</h3><div>A significant negative association between AAM and NAFLD was found in Model 3 (OR = 0.85, 95 % CI: 0.74–0.97). Participants in the highest AAM quintile exhibited a 68 % reduction of NAFLD prevalence compared to those in the lowest AAM quintile (OR = 0.32, 95 % CI: 0.11–0.97). MR analysis confirmed a potential negative causal association (discovery: OR = 0.81, 95 % CI: 0.73–0.90; validation: OR = 0.80, 95 % CI: 0.66–0.96).</div></div><div><h3>Conclusions</h3><div>Our findings indicate a potential causal association between AAM and NAFLD, suggesting that early AAM may serve as a potential risk marker for NAFLD. This highlights the importance of incorporating AAM into clinical risk assessment tools and developing targeted prevention strategies for at-risk populations. Further research is needed to clarify the underlying mechanisms and to explore the potential benefits of early intervention.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"204 ","pages":"Article 112748"},"PeriodicalIF":3.9,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143790994","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}