Experimental gerontology最新文献_第4页

Telomere length and metabolic dysfunction-associated steatotic liver disease risk and progression: A systematic review and meta-analysis 端粒长度与代谢功能障碍相关的脂肪变性肝病的风险和进展：一项系统回顾和荟萃分析

IF 4.3

Experimental gerontology

Pub Date : 2026-01-14 DOI: 10.1016/j.exger.2026.113036

Chunfeng Sun , Ping Qiu , Shuo Huang , Qihan Luo , Qing Ma , Piao Hu , Fangming Chen , Hongyan Wu , Chunxiao Chen

Aims

This study aims to systematically review existing literature to evaluate the association between telomere length (TL) and the risk of MASLD and its progression outcomes.

Materials and methods

PubMed, EMBASE, and Web of Science were searched for relevant studies up to May 27, 2025. Included studies were systematically reviewed to summarize the findings, with complementary quantitative analyses conducted using a random-effects model. This study was conducted in strict accordance with the PRISMA 2020 statement and was registered on the PROSPERO platform (CRD420251042478).

Results

Ultimately, 12 observational studies met the inclusion criteria. A limited number of high-quality cohort studies have consistently observed an association between shorter leukocyte TL (LTL) and an increased risk of MASLD. Evidence from cross-sectional studies appears more inconsistent and imprecise. Notably, cross-sectional analysis revealed a paradoxical increase in LTL among T2DM patients with MASLD, possibly reflecting a compensatory response to early-stage metabolic stress and insulin resistance; however, longitudinal evidence clarified that accelerated LTL attrition, rather than baseline length, serves as the critical driver and predictor of MASLD incidence. Despite consistent evidence indicating that shorter LTL may serve as a biomarker for severe MASLD progression, the interpretation of these findings is hampered by methodological limitations in current studies.

Conclusion

Current evidence suggests that shorter TL is a potential marker for MASLD risk, particularly supported by high-quality longitudinal data. While further quantitative analysis identified significant associations, the robustness of these results is compromised by the limited number of high-quality studies, alongside substantial heterogeneity and publication bias. Shorter TL may be associated with the adverse progression of MASLD. Future high-quality longitudinal studies are warranted to strengthen the body of evidence and establish their clinical utility.

本研究旨在系统地回顾现有文献，以评估端粒长度（TL）与MASLD风险及其进展结局之间的关系。检索截止到2025年5月27日的spubmed、EMBASE和Web of Science相关研究。系统回顾纳入的研究以总结研究结果，并使用随机效应模型进行补充性定量分析。本研究严格按照PRISMA 2020声明进行，并在PROSPERO平台上注册（CRD420251042478）。结果最终有12项观察性研究符合纳入标准。数量有限的高质量队列研究一致地观察到较短的白细胞TL （LTL）与MASLD风险增加之间的关联。来自横断面研究的证据似乎更不一致和不精确。值得注意的是，横断面分析揭示了T2DM合并MASLD患者LTL的矛盾增加，可能反映了对早期代谢应激和胰岛素抵抗的代偿反应；然而，纵向证据表明，加速LTL磨损，而不是基线长度，是MASLD发病率的关键驱动因素和预测因素。尽管一致的证据表明较短的LTL可能作为严重MASLD进展的生物标志物，但这些发现的解释受到当前研究方法限制的阻碍。结论：目前的证据表明，较短的TL是MASLD风险的潜在标志，特别是高质量的纵向数据支持。虽然进一步的定量分析确定了显著的关联，但这些结果的稳健性受到高质量研究数量有限、异质性和发表偏倚的影响。较短的生存期可能与MASLD的不良进展有关。未来有必要进行高质量的纵向研究，以加强证据体系并建立其临床应用。

{"title":"Telomere length and metabolic dysfunction-associated steatotic liver disease risk and progression: A systematic review and meta-analysis","authors":"Chunfeng Sun , Ping Qiu , Shuo Huang , Qihan Luo , Qing Ma , Piao Hu , Fangming Chen , Hongyan Wu , Chunxiao Chen","doi":"10.1016/j.exger.2026.113036","DOIUrl":"10.1016/j.exger.2026.113036","url":null,"abstract":"<div><h3>Aims</h3><div>This study aims to systematically review existing literature to evaluate the association between telomere length (TL) and the risk of MASLD and its progression outcomes.</div></div><div><h3>Materials and methods</h3><div>PubMed, EMBASE, and Web of Science were searched for relevant studies up to May 27, 2025. Included studies were systematically reviewed to summarize the findings, with complementary quantitative analyses conducted using a random-effects model. This study was conducted in strict accordance with the PRISMA 2020 statement and was registered on the PROSPERO platform (CRD420251042478).</div></div><div><h3>Results</h3><div>Ultimately, 12 observational studies met the inclusion criteria. A limited number of high-quality cohort studies have consistently observed an association between shorter leukocyte TL (LTL) and an increased risk of MASLD. Evidence from cross-sectional studies appears more inconsistent and imprecise. Notably, cross-sectional analysis revealed a paradoxical increase in LTL among T2DM patients with MASLD, possibly reflecting a compensatory response to early-stage metabolic stress and insulin resistance; however, longitudinal evidence clarified that accelerated LTL attrition, rather than baseline length, serves as the critical driver and predictor of MASLD incidence. Despite consistent evidence indicating that shorter LTL may serve as a biomarker for severe MASLD progression, the interpretation of these findings is hampered by methodological limitations in current studies.</div></div><div><h3>Conclusion</h3><div>Current evidence suggests that shorter TL is a potential marker for MASLD risk, particularly supported by high-quality longitudinal data. While further quantitative analysis identified significant associations, the robustness of these results is compromised by the limited number of high-quality studies, alongside substantial heterogeneity and publication bias. Shorter TL may be associated with the adverse progression of MASLD. Future high-quality longitudinal studies are warranted to strengthen the body of evidence and establish their clinical utility.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"214 ","pages":"Article 113036"},"PeriodicalIF":4.3,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145979552","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}

引用次数: 0

Comparing predictive energy-expenditure equations with indirect calorimetry in older adults living in long-term care facilities 长期护理机构中老年人预测能量消耗方程与间接量热法的比较。

IF 4.3

Experimental gerontology

Pub Date : 2026-01-14 DOI: 10.1016/j.exger.2026.113037

Katarzyna Zadka , Krzysztof Ławiński , Natalia Grodzicka , Atanas G. Atanasov , Michał Ławiński

Objective

Accurate estimation of resting energy expenditure (REE) in long-term care facilities (LTCFs) is challenging, and indirect calorimetry (IC) is seldom available. This cross-sectional study assessed the agreement between predictive equations and IC in older adults residing in LTCFs.

Research methods & procedures

REE was measured by IC and compared with estimates from 22 predictive equations. Agreement was evaluated using linear regression (R²), root mean square error (RMSE), Bland–Altman analysis, individual-level accuracy (90–110% of measured REE), mean percentage bias (%Bias), Lin's concordance correlation coefficient (CCC), and extreme prediction errors.

Results

A total of 182 residents were enrolled (72% women; mean age 81.24 ± 9.21 years; BMI 23.05 ± 5.11 kg/m²). Across equations, R² ranged from 0.24 to 0.41, RMSE from 230 to 317 kcal/d, and individual accuracy from 27% to 45%. Mean percentage bias ranged from –6% to +18%, indicating systematic under- and overestimation across models. The most consistent overall performance was observed for Lührmann, Müller, and Liu equations. Nonetheless, Bland–Altman analysis revealed wide limits of agreement, and CCC values indicating poor-to-moderate concordance (0.465–0.624). Several equations also produced extreme errors, demonstrating limited interchangeability with IC at the individual level.

Conclusion(s)

In people living in LTCFs, predictive equations showed modest explanatory power and low individual accuracy, with wide limits of agreement indicating that none can reliably replace IC when precise estimation of REE is required. Clinically, predicted REE should be regarded as an estimate rather than a dose, requiring cautious adjustment and verification against short-term monitoring of body weight, intake, and clinical status. When precise energy dosing is critical, IC should be used whenever feasible.

目的：准确估计长期护理设施（ltcf）的静息能量消耗（REE）具有挑战性，间接量热法（IC）很少可用。本横断面研究评估了居住在ltcf中的老年人预测方程和IC之间的一致性。研究方法和程序：REE采用IC测量，并比较了22个预测方程的估计值。采用线性回归（R2）、均方根误差（RMSE）、Bland-Altman分析、个体水平精度（测量REE的90-110%）、平均百分比偏差（% bias）、Lin’s一致性相关系数（CCC）和极端预测误差来评估一致性。结果：共纳入182名居民（72%为女性，平均年龄81.24 ± 9.21 岁，BMI 23.05 ± 5.11 kg/m2）。在各个方程中，R2范围为0.24至0.41，RMSE范围为230至317 kcal/d，个体精度范围为27%至45%。平均百分比偏差范围从-6%到+18%，表明模型中存在系统性的低估和高估。对于l hrmann, m ller和Liu方程，观察到最一致的总体性能。尽管如此，Bland-Altman分析显示了广泛的一致性限制，CCC值表明低至中等的一致性（0.465-0.624）。几个方程也产生了超过±1100 kcal/d的极端误差，表明在个人水平上与IC的互换性有限。结论：在生活在ltcf中的人群中，预测方程显示出适度的解释力和较低的个体准确性，具有广泛的一致性，表明当需要精确估计REE时，没有一个方程可以可靠地取代IC。在临床上，pREE应被视为一个估计值，而不是一个剂量，需要根据体重、摄入量和临床状况的短期监测进行谨慎的调整和验证。当精确的能量剂量至关重要时，应尽可能使用集成电路。

{"title":"Comparing predictive energy-expenditure equations with indirect calorimetry in older adults living in long-term care facilities","authors":"Katarzyna Zadka , Krzysztof Ławiński , Natalia Grodzicka , Atanas G. Atanasov , Michał Ławiński","doi":"10.1016/j.exger.2026.113037","DOIUrl":"10.1016/j.exger.2026.113037","url":null,"abstract":"<div><h3>Objective</h3><div>Accurate estimation of resting energy expenditure (REE) in long-term care facilities (LTCFs) is challenging, and indirect calorimetry (IC) is seldom available. This cross-sectional study assessed the agreement between predictive equations and IC in older adults residing in LTCFs.</div></div><div><h3>Research methods & procedures</h3><div>REE was measured by IC and compared with estimates from 22 predictive equations. Agreement was evaluated using linear regression (R<sup>2</sup>), root mean square error (RMSE), Bland–Altman analysis, individual-level accuracy (90–110% of measured REE), mean percentage bias (%Bias), Lin's concordance correlation coefficient (CCC), and extreme prediction errors.</div></div><div><h3>Results</h3><div>A total of 182 residents were enrolled (72% women; mean age 81.24 ± 9.21 years; BMI 23.05 ± 5.11 kg/m<sup>2</sup>). Across equations, R<sup>2</sup> ranged from 0.24 to 0.41, RMSE from 230 to 317 kcal/d, and individual accuracy from 27% to 45%. Mean percentage bias ranged from –6% to +18%, indicating systematic under- and overestimation across models. The most consistent overall performance was observed for Lührmann, Müller, and Liu equations. Nonetheless, Bland–Altman analysis revealed wide limits of agreement, and CCC values indicating poor-to-moderate concordance (0.465–0.624). Several equations also produced extreme errors, demonstrating limited interchangeability with IC at the individual level.</div></div><div><h3>Conclusion(s)</h3><div>In people living in LTCFs, predictive equations showed modest explanatory power and low individual accuracy, with wide limits of agreement indicating that none can reliably replace IC when precise estimation of REE is required. Clinically, predicted REE should be regarded as an estimate rather than a dose, requiring cautious adjustment and verification against short-term monitoring of body weight, intake, and clinical status. When precise energy dosing is critical, IC should be used whenever feasible.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"214 ","pages":"Article 113037"},"PeriodicalIF":4.3,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145992354","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}

引用次数: 0

Exploring the molecular intersections of osteoporosis and sarcopenia: An integrated bioinformatics and experimental validation 探索骨质疏松症和肌肉减少症的分子交叉：综合生物信息学和实验验证

IF 4.3

Experimental gerontology

Pub Date : 2026-01-12 DOI: 10.1016/j.exger.2026.113033

Yan Lv , Yongjun Du , Peng Lin , Jiamian Liu , Shaoquan Pu , Sheng Lu

Background

Osteoporosis and sarcopenia are age-related degenerative diseases that frequently co-occur in the older adults, yet their shared molecular mechanisms remain poorly understood. This study aimed to identify common biomarkers.

Methods

By utilizing the GEO database, differential and enrichment analyses were conducted to identify genes that are commonly expressed in both diseases. Subsequently, key genes were identified through four types of machine learning and six types of immune infiltration analyses. Finally, the Dual Condition Sarcopenia and Osteoporosis (DSO) model was established by combining bilateral ovariectomy with natural aging to validate the key genes.

Results

A total of 577 and 625 genes were identified in the osteoporosis (GSE156508) and sarcopenia (GSE226151), respectively. GO, KEGG, and GSEA analyses revealed that osteoporosis-related genes were enriched in muscle development and myogenesis pathways, while sarcopenia-related genes were linked to osteoclast differentiation and inflammatory responses. Venn analysis identified 20 genes shared by both diseases. Four machine learning algorithms identified five key genes: APOC1, ENPP5, FBXL22, IRS1, and PAQR4. Among them, PAQR4 showed the highest predictive value in ROC analysis and was consistently downregulated in both training and validation datasets. Immune infiltration analysis indicated altered neutrophil levels, notably reduced in osteoporotic skeletal muscle. Experimental validation confirmed decreased PAQR4 expression in both bone and muscle tissues of the DSO model.

Conclusions

These findings highlight PAQR4 as a potential biomarker and a candidate molecule of interest for osteosarcopenia.

背景：骨质疏松症和肌肉减少症是老年人常见的与年龄相关的退行性疾病，但其共同的分子机制尚不清楚。本研究旨在鉴定常见的生物标志物。方法利用GEO数据库，进行差异和富集分析，鉴定两种疾病中共同表达的基因。随后，通过四种类型的机器学习和六种类型的免疫浸润分析，确定了关键基因。最后，通过双侧卵巢切除与自然衰老相结合的方法建立双状态骨骼肌减少症和骨质疏松症（DSO）模型，验证关键基因。结果在骨质疏松症（GSE156508）和肌肉减少症（GSE226151）中分别鉴定出577个和625个基因。GO、KEGG和GSEA分析显示，骨质疏松相关基因在肌肉发育和肌肉形成途径中富集，而肌肉减少相关基因与破骨细胞分化和炎症反应有关。维恩分析确定了这两种疾病共有的20个基因。四种机器学习算法确定了五个关键基因：APOC1、ENPP5、FBXL22、IRS1和PAQR4。其中，PAQR4在ROC分析中预测价值最高，在训练数据集和验证数据集中均持续下调。免疫浸润分析显示中性粒细胞水平改变，骨质疏松骨骼肌明显减少。实验验证证实，PAQR4在DSO模型骨组织和肌肉组织中的表达均降低。这些发现突出了PAQR4作为一种潜在的生物标志物和骨骼肌减少症的候选分子。

{"title":"Exploring the molecular intersections of osteoporosis and sarcopenia: An integrated bioinformatics and experimental validation","authors":"Yan Lv , Yongjun Du , Peng Lin , Jiamian Liu , Shaoquan Pu , Sheng Lu","doi":"10.1016/j.exger.2026.113033","DOIUrl":"10.1016/j.exger.2026.113033","url":null,"abstract":"<div><h3>Background</h3><div>Osteoporosis and sarcopenia are age-related degenerative diseases that frequently co-occur in the older adults, yet their shared molecular mechanisms remain poorly understood. This study aimed to identify common biomarkers.</div></div><div><h3>Methods</h3><div>By utilizing the GEO database, differential and enrichment analyses were conducted to identify genes that are commonly expressed in both diseases. Subsequently, key genes were identified through four types of machine learning and six types of immune infiltration analyses. Finally, the Dual Condition Sarcopenia and Osteoporosis (DSO) model was established by combining bilateral ovariectomy with natural aging to validate the key genes.</div></div><div><h3>Results</h3><div>A total of 577 and 625 genes were identified in the osteoporosis (GSE156508) and sarcopenia (GSE226151), respectively. GO, KEGG, and GSEA analyses revealed that osteoporosis-related genes were enriched in muscle development and myogenesis pathways, while sarcopenia-related genes were linked to osteoclast differentiation and inflammatory responses. Venn analysis identified 20 genes shared by both diseases. Four machine learning algorithms identified five key genes: APOC1, ENPP5, FBXL22, IRS1, and PAQR4. Among them, PAQR4 showed the highest predictive value in ROC analysis and was consistently downregulated in both training and validation datasets. Immune infiltration analysis indicated altered neutrophil levels, notably reduced in osteoporotic skeletal muscle. Experimental validation confirmed decreased PAQR4 expression in both bone and muscle tissues of the DSO model.</div></div><div><h3>Conclusions</h3><div>These findings highlight PAQR4 as a potential biomarker and a candidate molecule of interest for osteosarcopenia.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"214 ","pages":"Article 113033"},"PeriodicalIF":4.3,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145979553","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}

引用次数: 0

Effect of cognitive and motor dual-task on stability and variability of walking in younger and older adults 认知和运动双重任务对年轻人和老年人行走稳定性和变异性的影响

IF 4.3

Experimental gerontology

Pub Date : 2026-01-12 DOI: 10.1016/j.exger.2026.113035

Jay Barolo , Douglas Mitchell , Francesca E. Wade

Dual-task walking, performing a secondary task while walking, challenges attentional and motor resources and has been linked to increased fall risk. While cognitive dual tasks are most often studied, physical (e.g., load carriage) and “combination” tasks such as obstacle crossing may also impact gait. Whole-body angular momentum and its variability provide sensitive markers of locomotor stability. We investigated how dual-task type influences gait mechanics and stability in younger and older adults.

Sixteen adults (18–80 years) completed four treadmill conditions at preferred walking speed: baseline walking (PWS), walking while talking (WWT), box carriage (BOX, 15 lb), and obstacle crossing (OBS). Spatiotemporal measures, trailing limb angle (TLA), and whole-body angular momentum in frontal and sagittal planes were computed. Mixed-model ANOVAs and statistical parametric mapping assessed trial and age effects.

Dual tasks altered spatiotemporal gait. BOX and OBS reduced step length, and OBS also shortened step time and reduced late-stance TLA. OBS elicited consistently greater variability in step length, width, time, double-support, and whole body angular momentum in both planes (all p < .01). Older adults took shorter steps and longer double support, with age × task interactions observed in these metrics.

Obstacle crossing imposed the greatest locomotor challenge, producing significant changes in TLA, whole body angular momentum, and variability, whereas cognitive and load carriage tasks induced smaller deviations. Findings highlight the importance of incorporating ecologically relevant “combination” tasks into gait assessment and demonstrate the utility of time-series analyses for detecting phase-specific disruptions to locomotor stability.

双任务行走，即在行走时进行第二项任务，会挑战注意力和运动资源，并与跌倒风险增加有关。虽然最常研究的是认知双重任务，但体力（如负重）和“组合”任务（如穿越障碍）也可能影响步态。全身角动量及其变异性是运动稳定性的敏感标志。我们研究了双任务类型如何影响年轻人和老年人的步态力学和稳定性。16名成年人（18-80岁）以首选的步行速度完成四种跑步机条件：基线步行（PWS），边走边说（WWT），箱子运输（box， 15磅）和障碍穿越（OBS）。计算时空测量、后肢角（TLA）和全身正矢状面角动量。混合模型方差分析和统计参数映射评估试验和年龄效应。双重任务改变时空步态。BOX和OBS均缩短了步长，OBS也缩短了步长时间，降低了后期TLA。OBS在两个平面的步长、宽度、时间、双支撑和全身角动量方面都引起了更大的变异性（均p <； 0.01）。在这些指标中观察到年龄×任务的相互作用，老年人的步数较短，双人支撑时间较长。越障对运动能力的挑战最大，导致TLA、全身角动量和变异性发生显著变化，而认知和负重任务引起的偏差较小。研究结果强调了将生态相关的“组合”任务纳入步态评估的重要性，并证明了时间序列分析在检测特定阶段对运动稳定性的破坏方面的实用性。

{"title":"Effect of cognitive and motor dual-task on stability and variability of walking in younger and older adults","authors":"Jay Barolo , Douglas Mitchell , Francesca E. Wade","doi":"10.1016/j.exger.2026.113035","DOIUrl":"10.1016/j.exger.2026.113035","url":null,"abstract":"<div><div>Dual-task walking, performing a secondary task while walking, challenges attentional and motor resources and has been linked to increased fall risk. While cognitive dual tasks are most often studied, physical (e.g., load carriage) and “combination” tasks such as obstacle crossing may also impact gait. Whole-body angular momentum and its variability provide sensitive markers of locomotor stability. We investigated how dual-task type influences gait mechanics and stability in younger and older adults.</div><div>Sixteen adults (18–80 years) completed four treadmill conditions at preferred walking speed: baseline walking (PWS), walking while talking (WWT), box carriage (BOX, 15 lb), and obstacle crossing (OBS). Spatiotemporal measures, trailing limb angle (TLA), and whole-body angular momentum in frontal and sagittal planes were computed. Mixed-model ANOVAs and statistical parametric mapping assessed trial and age effects.</div><div>Dual tasks altered spatiotemporal gait. BOX and OBS reduced step length, and OBS also shortened step time and reduced late-stance TLA. OBS elicited consistently greater variability in step length, width, time, double-support, and whole body angular momentum in both planes (all <em>p</em> < .01). Older adults took shorter steps and longer double support, with age × task interactions observed in these metrics.</div><div>Obstacle crossing imposed the greatest locomotor challenge, producing significant changes in TLA, whole body angular momentum, and variability, whereas cognitive and load carriage tasks induced smaller deviations. Findings highlight the importance of incorporating ecologically relevant “combination” tasks into gait assessment and demonstrate the utility of time-series analyses for detecting phase-specific disruptions to locomotor stability.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"214 ","pages":"Article 113035"},"PeriodicalIF":4.3,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145979554","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}

引用次数: 0

Probucol attenuates bone loss in APP/PS1 mice and ameliorates Aβ42-induced osteoblast dysfunction by regulating AKT/FOXO3a signaling pathway Probucol通过调节AKT/FOXO3a信号通路，减轻APP/PS1小鼠骨质流失，改善a β42诱导的成骨细胞功能障碍。

IF 4.3

Experimental gerontology

Pub Date : 2026-01-12 DOI: 10.1016/j.exger.2026.113034

Dong Liu , Hongyan Yang , Xiangqian Feng , Mingliang Hou , Xiaoyan Fu , Xiaoxiong Li , Wenjuan Hong , Le Chen , Jinping Li , Linqiu Ma , Qirong Liao , Yating Liu , Jing Lu , Donglin Wang , Huadong Zhou , Rui Zhou

Background

Alzheimer's disease (AD) and osteoporosis are common age-related degenerative diseases. Emerging evidence suggests that amyloid-β (Aβ) deposition may contribute to the pathogenesis of both conditions. This study investigated whether probucol could alleviate AD-associated bone loss and Aβ42-induced osteoblast dysfunction, and further explored the underlying mechanisms.

Methods

Female mice were divided into four groups (n = 5 per group): C57BL/6 wild-type (WT), WT treated with probucol (WT + PBC), APP/PS1 transgenic (AD) mice, and AD treated with probucol (AD+PBC). Bone mineral density (BMD) was assessed by micro-CT. Levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) along with bone metabolism markers including fibroblast growth factor 23 (FGF23), sclerostin, and brain-derived neurotrophic factor (BDNF) in bone and brain tissues were measured by ELISA. FOXO3a was knocked down in the bone marrow of APP/PS1 mice via stereotactic injection of lentiviral vectors. Expression of APP and FOXO3a in bone tissue was evaluated using RT-qPCR and Western blotting (WB). Mitochondrial damage in osteoblasts and neuronal cells was assessed by transmission electron microscopy (TEM). In vitro study, osteoblast differentiation and mineralization deficits were evaluated using Alizarin Red staining. WB was used to measure the expression of AKT, FOXO3a, autophagy and apoptosis related proteins.

Results

Probucol attenuated bone loss and mitochondrial damage in both APP/PS1 and FOXO3a-knockdown APP/PS1 mice, and improved cognitive impairment and neuronal ultrastructure in APP/PS1 mice. Furthermore, probucol attenuated Aβ42-induced osteoblast differentiation and mineralization via the AKT/FOXO3a signaling pathway in vitro.

Conclusion

These findings demonstrate that probucol ameliorates AD-associated bone loss and Aβ42-induced osteoblast impairments by regulating AKT/FOXO3a signaling pathway.

背景：阿尔茨海默病（AD）和骨质疏松症是常见的与年龄相关的退行性疾病。新出现的证据表明，淀粉样蛋白-β (Aβ)沉积可能有助于这两种疾病的发病机制。本研究探讨普罗布考是否能减轻ad相关性骨质流失和a β42诱导的成骨细胞功能障碍，并进一步探讨其机制。方法：将雌性小鼠分为4组（每组 = 5只）：C57BL/6野生型（WT）、普罗布科尔处理的WT （WT + PBC）、APP/PS1转基因（AD）小鼠和普罗布科尔处理的AD （AD+PBC）。显微ct检查骨密度（BMD）。ELISA法检测骨、脑组织中促炎因子（IL-1β、IL-6、TNF-α）及骨代谢标志物（成纤维细胞生长因子23 （FGF23）、硬化蛋白、脑源性神经营养因子（BDNF））水平。通过立体定向注射慢病毒载体，在APP/PS1小鼠骨髓中敲除FOXO3a。应用RT-qPCR和Western blotting （WB）检测骨组织中APP和FOXO3a的表达。透射电镜观察成骨细胞和神经细胞线粒体损伤情况。体外研究，用茜素红染色评价成骨细胞分化和矿化缺陷。WB检测AKT、FOXO3a、自噬及凋亡相关蛋白的表达。结果：普罗布考均能减轻APP/PS1小鼠和foxo3a敲除APP/PS1小鼠的骨质流失和线粒体损伤，改善APP/PS1小鼠的认知功能障碍和神经元超微结构。此外，普罗布考在体外通过AKT/FOXO3a信号通路减弱a β42诱导的成骨细胞分化和矿化。结论：probucol通过调节AKT/FOXO3a信号通路改善ad相关骨质流失和a - β42诱导的成骨细胞损伤。

{"title":"Probucol attenuates bone loss in APP/PS1 mice and ameliorates Aβ42-induced osteoblast dysfunction by regulating AKT/FOXO3a signaling pathway","authors":"Dong Liu , Hongyan Yang , Xiangqian Feng , Mingliang Hou , Xiaoyan Fu , Xiaoxiong Li , Wenjuan Hong , Le Chen , Jinping Li , Linqiu Ma , Qirong Liao , Yating Liu , Jing Lu , Donglin Wang , Huadong Zhou , Rui Zhou","doi":"10.1016/j.exger.2026.113034","DOIUrl":"10.1016/j.exger.2026.113034","url":null,"abstract":"<div><h3>Background</h3><div>Alzheimer's disease (AD) and osteoporosis are common age-related degenerative diseases. Emerging evidence suggests that amyloid-β (Aβ) deposition may contribute to the pathogenesis of both conditions. This study investigated whether probucol could alleviate AD-associated bone loss and Aβ42-induced osteoblast dysfunction, and further explored the underlying mechanisms.</div></div><div><h3>Methods</h3><div>Female mice were divided into four groups (<em>n</em> = 5 per group): C57BL/6 wild-type (WT), WT treated with probucol (WT + PBC), APP/PS1 transgenic (AD) mice, and AD treated with probucol (AD+PBC). Bone mineral density (BMD) was assessed by micro-CT. Levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) along with bone metabolism markers including fibroblast growth factor 23 (FGF23), sclerostin, and brain-derived neurotrophic factor (BDNF) in bone and brain tissues were measured by ELISA. FOXO3a was knocked down in the bone marrow of APP/PS1 mice via stereotactic injection of lentiviral vectors. Expression of APP and FOXO3a in bone tissue was evaluated using RT-qPCR and Western blotting (WB). Mitochondrial damage in osteoblasts and neuronal cells was assessed by transmission electron microscopy (TEM). In vitro study, osteoblast differentiation and mineralization deficits were evaluated using Alizarin Red staining. WB was used to measure the expression of AKT, FOXO3a, autophagy and apoptosis related proteins.</div></div><div><h3>Results</h3><div>Probucol attenuated bone loss and mitochondrial damage in both APP/PS1 and FOXO3a-knockdown APP/PS1 mice, and improved cognitive impairment and neuronal ultrastructure in APP/PS1 mice. Furthermore, probucol attenuated Aβ42-induced osteoblast differentiation and mineralization via the AKT/FOXO3a signaling pathway in vitro.</div></div><div><h3>Conclusion</h3><div>These findings demonstrate that probucol ameliorates AD-associated bone loss and Aβ42-induced osteoblast impairments by regulating AKT/FOXO3a signaling pathway.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"214 ","pages":"Article 113034"},"PeriodicalIF":4.3,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145986109","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}

引用次数: 0

Muscle ultrasonography texture in young, middle-aged, and older people and its association with functional performance: A machine learning-based study 年轻人、中年人和老年人的肌肉超声纹理及其与功能表现的关系：一项基于机器学习的研究。

IF 4.3

Experimental gerontology

Pub Date : 2026-01-11 DOI: 10.1016/j.exger.2026.113029

Chaoran Liu , Hui Shen , Kai Zhang , Xiumei Zhang , Rui Wang , Ninghua Wang

Background

Skeletal muscle deterioration accelerates with age, leading to muscle atrophy and dysfunction. Musculoskeletal ultrasound as a nonradiative, inexpensive, and portable tool, has potential to evaluate age-related muscle changes. This study aims to detect age-related muscle features based on muscle texture analysis and machine learning approach, and to investigate muscle features that are related to function.

Methods

Healthy adults were recruited and divided into young, middle-aged, and older groups. 3 muscle architecture and 154 texture features were extracted from transverse (T) and longitudinal (L) ultrasonic images of muscle. Reliability analysis of all texture features was performed. Support vector machine recursive feature elimination (SVM-RFE) was utilized to identify age-related muscle parameters. Muscle features as contributors of muscle function measured by 4 performance tests were detected.

Results

113 participants were recruited. The inter-rater and test-retest reliability showed that 44 muscle ultrasonography texture features were reliable. Among them, 9 features including gray variance-T, 0°short run low gray-level emphasis-T, inertia-L, 0°short run emphasis-T, gray variance-L, gray average-L, 0°run percentage-T, 45°energy-T, and 0°low gray-level run emphasis-L could be used to classify young and older groups with the accuracy of 94.04%, and sensitivity of 93.33% by SVM-RFE. In the multivariate analysis, 3 texture features contributed to functional performance. Gradient mean variance has the highest predictive value.

Conclusion

Texture analysis combined with machine learning could provide non-invasive biomarkers to classify muscles of young and old individuals, and assist in function prediction.

背景：骨骼肌退化随着年龄的增长而加速，导致肌肉萎缩和功能障碍。肌肉骨骼超声作为一种非辐射、廉价、便携的工具，具有评估与年龄相关的肌肉变化的潜力。本研究旨在基于肌肉纹理分析和机器学习方法检测与年龄相关的肌肉特征，并研究与功能相关的肌肉特征。方法：招募健康成人，分为青年、中年和老年三组。从肌肉的横向(T)和纵向(L)超声图像中提取了3个肌肉结构和154个纹理特征。对所有纹理特征进行了可靠性分析。采用支持向量机递归特征消除（SVM-RFE）识别年龄相关肌肉参数。通过4项性能测试检测肌肉特征对肌肉功能的贡献。结果：招募了113名参与者。测间信度和重测信度表明44个肌肉超声纹理特征是可靠的。其中，灰度方差- t、0°短时低灰度强调- t、惯性-l、0°短时强调- t、灰度方差-l、灰度平均-l、0°运行百分比- t、45°能量- t、0°低灰度强调-l 9个特征可用于青年和老年群体的分类，SVM-RFE的准确率为94.04%，灵敏度为93.33%。在多变量分析中，有3种纹理特征对功能性能有贡献。梯度均值方差的预测值最高。结论：肌理分析与机器学习相结合，可提供无创生物标记物对年轻人和老年人的肌肉进行分类，并有助于功能预测。

{"title":"Muscle ultrasonography texture in young, middle-aged, and older people and its association with functional performance: A machine learning-based study","authors":"Chaoran Liu , Hui Shen , Kai Zhang , Xiumei Zhang , Rui Wang , Ninghua Wang","doi":"10.1016/j.exger.2026.113029","DOIUrl":"10.1016/j.exger.2026.113029","url":null,"abstract":"<div><h3>Background</h3><div>Skeletal muscle deterioration accelerates with age, leading to muscle atrophy and dysfunction. Musculoskeletal ultrasound as a nonradiative, inexpensive, and portable tool, has potential to evaluate age-related muscle changes. This study aims to detect age-related muscle features based on muscle texture analysis and machine learning approach, and to investigate muscle features that are related to function.</div></div><div><h3>Methods</h3><div>Healthy adults were recruited and divided into young, middle-aged, and older groups. 3 muscle architecture and 154 texture features were extracted from transverse (T) and longitudinal (L) ultrasonic images of muscle. Reliability analysis of all texture features was performed. Support vector machine recursive feature elimination (SVM-RFE) was utilized to identify age-related muscle parameters. Muscle features as contributors of muscle function measured by 4 performance tests were detected.</div></div><div><h3>Results</h3><div>113 participants were recruited. The inter-rater and test-retest reliability showed that 44 muscle ultrasonography texture features were reliable. Among them, 9 features including gray variance-T, 0°short run low gray-level emphasis-T, inertia-L, 0°short run emphasis-T, gray variance-L, gray average-L, 0°run percentage-T, 45°energy-T, and 0°low gray-level run emphasis-L could be used to classify young and older groups with the accuracy of 94.04%, and sensitivity of 93.33% by SVM-RFE. In the multivariate analysis, 3 texture features contributed to functional performance. Gradient mean variance has the highest predictive value.</div></div><div><h3>Conclusion</h3><div>Texture analysis combined with machine learning could provide non-invasive biomarkers to classify muscles of young and old individuals, and assist in function prediction.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"214 ","pages":"Article 113029"},"PeriodicalIF":4.3,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145967148","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}

引用次数: 0

Predictive value of remnant cholesterol inflammatory index for cardiovascular-kidney-metabolic syndrome progression: A prospective cohort study 残余胆固醇炎症指数对心血管-肾-代谢综合征进展的预测价值：一项前瞻性队列研究。

IF 4.3

Experimental gerontology

Pub Date : 2026-01-10 DOI: 10.1016/j.exger.2026.113030

Xiaoying Ren , Yong Tian , Juan Tian , Guang Wang , Jia Liu

Background

Cardiovascular-kidney-metabolic (CKM) syndrome is a progressive disorder resulting from the intricate interactions among obesity, diabetes, chronic kidney disease (CKD), and cardiovascular disease (CVD). Remnant cholesterol (RC) has been shown to be associated with the risk of CKM syndrome progression. However, the combined effects of RC and high-sensitivity C-reactive protein (hs-CRP) on CKM syndrome progression remain unclear. This study evaluated the association between the remnant cholesterol inflammatory index (RCII) and CKM progression risk.

Methods

Data from the China Health and Retirement Longitudinal Study (CHARLS) were analyzed. Logistic regression models were employed to investigate the association between the baseline RCII and advanced CKM stages. Kaplan-Meier analysis was conducted to assess the cumulative incidence of CVD across RCII quartiles in individuals with CKM stages 0–3. Cox regression models were used to examine the associations of the baseline RCII and cumulative RCII (CumRCII) with the risk of new-onset CVD among individuals with CKM stages 0–3.

Results

In the baseline analysis, each standard deviation (SD) increase in the RCII was associated with a 26% greater risk of advanced CKM stages (odds ratio (OR): 1.26, 95% CI: 1.20–1.34). During the 7-year follow-up, 1483 (21.5%) participants with CKM stages 0–3 developed CVD. The cumulative incidence of CVD progressively increased across RCII quartiles, from 17.02% in Q1 to 25.75% in Q4. After full adjustment, compared with that in RCII Q1, CVD risk was 19% greater in RCII Q3 (hazard ratio (HR): 1.19, 95% CI: 1.02–1.39) and 29% greater in RCII Q4 (HR: 1.29, 95% CI: 1.11–1.51). Participants with CumRCII levels that exceeded 29.49 had a significantly increased risk of new-onset CVD (HR: 1.41, 95% CI: 1.10–1.80).

Conclusions

Higher baseline RCII and CumRCII were associated with an increased CVD risk in participants with CKM stages 0–3. Early intervention in those with elevated RCII may help prevent CKM progression.

背景：心血管肾代谢综合征（CKM）是肥胖、糖尿病、慢性肾脏疾病（CKD）和心血管疾病（CVD）复杂相互作用的进行性疾病。残余胆固醇（RC）已被证明与CKM综合征进展的风险相关。然而，RC和高敏c反应蛋白（hs-CRP）在CKM综合征进展中的联合作用尚不清楚。本研究评估了残余胆固醇炎症指数（RCII）与CKM进展风险之间的关系。方法：对中国健康与退休纵向研究（CHARLS）的数据进行分析。采用Logistic回归模型研究基线RCII与CKM晚期之间的关系。Kaplan-Meier分析用于评估CKM 0-3期个体RCII四分位数中CVD的累积发病率。使用Cox回归模型检查0-3期CKM患者的基线和累积RCII （CumRCII）与新发CVD风险的关系。结果：在基线分析中，RCII的每一个标准差（SD）增加与晚期CKM的风险增加26%相关（优势比（OR）： 1.26, 95% CI: 1.20-1.34）。在7年的随访中，1483名（21.5%）CKM 0-3期参与者发展为CVD。CVD的累积发病率在RCII四分位数中逐渐增加，从第一季度的17.02%增加到第四季度的25.75%。完全调整后，与RCII Q1相比，第三季度心血管疾病风险增加19%（风险比（HR）： 1.19, 95% CI: 1.02-1.39），第四季度心血管疾病风险增加29% （HR: 1.29, 95% CI: 1.11-1.51）。CumRCII水平超过29.49的参与者患新发CVD的风险显著增加（HR: 1.41, 95% CI: 1.10-1.80）。结论：在0-3期CKM参与者中，较高的基线RCII和CumRCII与CVD风险增加相关。对RCII升高的患者进行早期干预可能有助于预防CKM进展。

{"title":"Predictive value of remnant cholesterol inflammatory index for cardiovascular-kidney-metabolic syndrome progression: A prospective cohort study","authors":"Xiaoying Ren , Yong Tian , Juan Tian , Guang Wang , Jia Liu","doi":"10.1016/j.exger.2026.113030","DOIUrl":"10.1016/j.exger.2026.113030","url":null,"abstract":"<div><h3>Background</h3><div>Cardiovascular-kidney-metabolic (CKM) syndrome is a progressive disorder resulting from the intricate interactions among obesity, diabetes, chronic kidney disease (CKD), and cardiovascular disease (CVD). Remnant cholesterol (RC) has been shown to be associated with the risk of CKM syndrome progression. However, the combined effects of RC and high-sensitivity C-reactive protein (hs-CRP) on CKM syndrome progression remain unclear. This study evaluated the association between the remnant cholesterol inflammatory index (RCII) and CKM progression risk.</div></div><div><h3>Methods</h3><div>Data from the China Health and Retirement Longitudinal Study (CHARLS) were analyzed. Logistic regression models were employed to investigate the association between the baseline RCII and advanced CKM stages. Kaplan-Meier analysis was conducted to assess the cumulative incidence of CVD across RCII quartiles in individuals with CKM stages 0–3. Cox regression models were used to examine the associations of the baseline RCII and cumulative RCII (CumRCII) with the risk of new-onset CVD among individuals with CKM stages 0–3.</div></div><div><h3>Results</h3><div>In the baseline analysis, each standard deviation (SD) increase in the RCII was associated with a 26% greater risk of advanced CKM stages (odds ratio (OR): 1.26, 95% CI: 1.20–1.34). During the 7-year follow-up, 1483 (21.5%) participants with CKM stages 0–3 developed CVD. The cumulative incidence of CVD progressively increased across RCII quartiles, from 17.02% in Q1 to 25.75% in Q4. After full adjustment, compared with that in RCII Q1, CVD risk was 19% greater in RCII Q3 (hazard ratio (HR): 1.19, 95% CI: 1.02–1.39) and 29% greater in RCII Q4 (HR: 1.29, 95% CI: 1.11–1.51). Participants with CumRCII levels that exceeded 29.49 had a significantly increased risk of new-onset CVD (HR: 1.41, 95% CI: 1.10–1.80).</div></div><div><h3>Conclusions</h3><div>Higher baseline RCII and CumRCII were associated with an increased CVD risk in participants with CKM stages 0<strong>–</strong>3. Early intervention in those with elevated RCII may help prevent CKM progression.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"214 ","pages":"Article 113030"},"PeriodicalIF":4.3,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145954737","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}

引用次数: 0

The association between dietary inflammation index and peripheral neuropathy: Insights into the role of biological aging from a cross-sectional NHANES study 饮食炎症指数与周围神经病变之间的关系：来自NHANES横断面研究的生物衰老作用的见解。

IF 4.3

Experimental gerontology

Pub Date : 2026-01-10 DOI: 10.1016/j.exger.2026.113031

Shishuang zhang , Han Gao , Yaru Liu , Yongle Zhi , Yu Du

Objectives

Peripheral neuropathy (PN) is a prevalent neurological disorder with significant health and socio-economic burdens. The Dietary Inflammatory Index (DII) systematically assesses the proinflammatory characteristics of dietary patterns. This study aimed to elucidate the complex relationships among DII, biological aging, and PN, and to deepen the understanding of the potential factors driving these associations, thereby providing novel insights for prevention and clinical intervention.

Methods

This study investigated the National Health and Nutrition Examination Survey 1999–2004 data. The linear association between DII and PN was assessed using binary logistic regression, while restricted cubic splines were employed to evaluate potential nonlinear relationships. Furthermore, mediation analysis was conducted to quantify the contribution of biological age in this association.

Results

This study enrolled and analyzed 7860 participants. DII revealed a significant correlation with the prevalence of PN (the odds ratio [OR] = 1.07, 95% confidence interval [CI]: 1.03–1.30, p < 0.001). A J-shaped nonlinear association was identified between DII and the PN (p = 0.0079), with an inflection point at 1.295. Beyond this threshold, OR significantly increased to 1.16 (95% CI: 1.03–1.30). Biological age contributed to 19.95% of the total association between DII and PN.

Conclusions

This study demonstrates a J-shaped association between DII and PN, which is partially accounted for by biological aging. These findings provide a new perspective for preventing PN through a low-inflammation diet.

目的：周围神经病变（PN）是一种常见的神经系统疾病，具有显著的健康和社会经济负担。膳食炎症指数（DII）系统地评估饮食模式的促炎特征。本研究旨在阐明DII、生物衰老和PN之间的复杂关系，并加深对驱动这些关联的潜在因素的理解，从而为预防和临床干预提供新的见解。方法：对1999-2004年全国健康与营养调查资料进行调查。使用二元逻辑回归评估DII和PN之间的线性关联，而限制三次样条则用于评估潜在的非线性关系。此外，还进行了中介分析，以量化生物年龄在这种关联中的作用。结果：本研究招募并分析了7860名参与者。DII与PN患病率有显著相关性（比值比[OR] = 1.07,95%可信区间[CI]: 1.03-1.30, p ）结论：本研究表明DII与PN之间呈j型相关，其中部分与生物衰老有关。这些发现为通过低炎症饮食预防PN提供了新的视角。

{"title":"The association between dietary inflammation index and peripheral neuropathy: Insights into the role of biological aging from a cross-sectional NHANES study","authors":"Shishuang zhang , Han Gao , Yaru Liu , Yongle Zhi , Yu Du","doi":"10.1016/j.exger.2026.113031","DOIUrl":"10.1016/j.exger.2026.113031","url":null,"abstract":"<div><h3>Objectives</h3><div>Peripheral neuropathy (PN) is a prevalent neurological disorder with significant health and socio-economic burdens. The Dietary Inflammatory Index (DII) systematically assesses the proinflammatory characteristics of dietary patterns. This study aimed to elucidate the complex relationships among DII, biological aging, and PN, and to deepen the understanding of the potential factors driving these associations, thereby providing novel insights for prevention and clinical intervention.</div></div><div><h3>Methods</h3><div>This study investigated the National Health and Nutrition Examination Survey 1999–2004 data. The linear association between DII and PN was assessed using binary logistic regression, while restricted cubic splines were employed to evaluate potential nonlinear relationships. Furthermore, mediation analysis was conducted to quantify the contribution of biological age in this association.</div></div><div><h3>Results</h3><div>This study enrolled and analyzed 7860 participants. DII revealed a significant correlation with the prevalence of PN (the odds ratio [OR] = 1.07, 95% confidence interval [CI]: 1.03–1.30, <em>p</em> < 0.001). A J-shaped nonlinear association was identified between DII and the PN (<em>p</em> = 0.0079), with an inflection point at 1.295. Beyond this threshold, OR significantly increased to 1.16 (95% CI: 1.03–1.30). Biological age contributed to 19.95% of the total association between DII and PN.</div></div><div><h3>Conclusions</h3><div>This study demonstrates a J-shaped association between DII and PN, which is partially accounted for by biological aging. These findings provide a new perspective for preventing PN through a low-inflammation diet.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"214 ","pages":"Article 113031"},"PeriodicalIF":4.3,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145961082","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}

引用次数: 0

Unmasking malnutrition through soluble RAGE: A biomarker-guided insight from FRASNET 通过可溶性RAGE揭示营养不良：来自FRASNET的生物标志物引导的见解。

IF 4.3

Experimental gerontology

Pub Date : 2026-01-10 DOI: 10.1016/j.exger.2026.113032

Sarah Damanti , Clara Sciorati , Amanda Avola , Rebecca De Lorenzo , Maria Pia Ruggiero , Simona Santoro , Eleonora Senini , Marco Messina , Francesca Farina , Costanza Festorazzi , Giulia Pata , Martina Laffranchi , Martina Mallus , Elena Brioni , Lorena Citterio , Laura Zagato , Marco Simonini , Chiara Lanzani , Paolo Manunta , Angelo Manfredi , Patrizia Rovere-Querini

Background

Malnutrition is a prevalent geriatric syndrome, with multifactorial etiology and consequences for health and independence. Inflammation contributes to nutritional decline, yet conventional inflammatory markers often lack sensitivity for identifying malnutrition risk. The soluble receptor for advanced glycation end-products (sRAGE), a modulator of inflammatory responses, has emerged as a biomarker of disease risk and adverse outcomes in various conditions.

Objectives

to evaluate the association between circulating sRAGE levels and nutritional status in community-dwelling older adults.

Methods

This prospective observational study was conducted within the FRASNET cohort. Fifty-two community-dwelling older adults underwent multidimensional geriatric assessments during two time periods: 2017–2020 and 2023–2024. Serum sRAGE levels were measured at both timepoints. Nutritional status was assessed using the Mini Nutritional Assessment Short Form (MNA-SF). Associations between sRAGE and clinical parameters were evaluated through linear regression models adjusted for age and sex. The diagnostic performance of sRAGE in identifying malnutrition was assessed using ROC curve analysis.

Results

Higher baseline sRAGE levels were significantly associated with lower BMI (β = −0.003, p = 0.036), reduced calf circumference (β = −0.002, p = 0.04), and poorer nutritional status as revealed by MNA-SF scores (β = −0.001, p = 0.03) at follow-up. Associations were more pronounced in women. ROC analysis indicated good diagnostic accuracy for identifying malnutrition risk, with an AUC of 0.85. The optimal sRAGE cut-off value for malnutrition risk was 1362.5 pg/ml.

Conclusions

Higher sRAGE levels were prospectively associated with poorer nutritional outcomes in older adults, particularly in women. sRAGE may aid early identification of inflammation-related malnutrition risk.

背景：营养不良是一种普遍的老年综合征，具有多因素的病因和对健康和独立的影响。炎症有助于营养下降，但传统的炎症标志物往往缺乏识别营养不良风险的敏感性。晚期糖基化终产物可溶性受体（sRAGE）是炎症反应的调节剂，已成为各种疾病风险和不良后果的生物标志物。目的：评估社区居住老年人循环sRAGE水平与营养状况之间的关系。方法：这项前瞻性观察性研究在FRASNET队列中进行。在2017-2020年和2023-2024年两个时间段内，52名社区居住的老年人接受了多维老年病学评估。在两个时间点测量血清sRAGE水平。采用迷你营养评估简表（MNA-SF）评估营养状况。通过调整年龄和性别的线性回归模型评估sRAGE与临床参数之间的关系。采用ROC曲线分析评价sRAGE对营养不良的诊断效果。结果:高基线sRAGE水平显著降低BMI(β = -0.003,p = 0.036),降低小腿周长(β = -0.002,p = 0.04),和贫穷的营养状况揭示了MNA-SF分数(β = -0.001,p = 0.03)在随访。这种关联在女性中更为明显。ROC分析显示，鉴别营养不良风险的诊断准确性良好，AUC为0.85。营养不良风险的最佳sRAGE临界值为1362.5 pg/mL。结论：较高的sRAGE水平与老年人（尤其是女性）较差的营养结局相关。sRAGE可能有助于早期识别炎症相关的营养不良风险。

{"title":"Unmasking malnutrition through soluble RAGE: A biomarker-guided insight from FRASNET","authors":"Sarah Damanti , Clara Sciorati , Amanda Avola , Rebecca De Lorenzo , Maria Pia Ruggiero , Simona Santoro , Eleonora Senini , Marco Messina , Francesca Farina , Costanza Festorazzi , Giulia Pata , Martina Laffranchi , Martina Mallus , Elena Brioni , Lorena Citterio , Laura Zagato , Marco Simonini , Chiara Lanzani , Paolo Manunta , Angelo Manfredi , Patrizia Rovere-Querini","doi":"10.1016/j.exger.2026.113032","DOIUrl":"10.1016/j.exger.2026.113032","url":null,"abstract":"<div><h3>Background</h3><div>Malnutrition is a prevalent geriatric syndrome, with multifactorial etiology and consequences for health and independence. Inflammation contributes to nutritional decline, yet conventional inflammatory markers often lack sensitivity for identifying malnutrition risk. The soluble receptor for advanced glycation end-products (sRAGE), a modulator of inflammatory responses, has emerged as a biomarker of disease risk and adverse outcomes in various conditions.</div></div><div><h3>Objectives</h3><div>to evaluate the association between circulating sRAGE levels and nutritional status in community-dwelling older adults.</div></div><div><h3>Methods</h3><div>This prospective observational study was conducted within the FRASNET cohort. Fifty-two community-dwelling older adults underwent multidimensional geriatric assessments during two time periods: 2017–2020 and 2023–2024. Serum sRAGE levels were measured at both timepoints. Nutritional status was assessed using the Mini Nutritional Assessment Short Form (MNA-SF). Associations between sRAGE and clinical parameters were evaluated through linear regression models adjusted for age and sex. The diagnostic performance of sRAGE in identifying malnutrition was assessed using ROC curve analysis.</div></div><div><h3>Results</h3><div>Higher baseline sRAGE levels were significantly associated with lower BMI (β = −0.003, <em>p</em> = 0.036), reduced calf circumference (β = −0.002, <em>p</em> = 0.04), and poorer nutritional status as revealed by MNA-SF scores (β = −0.001, p = 0.03) at follow-up. Associations were more pronounced in women. ROC analysis indicated good diagnostic accuracy for identifying malnutrition risk, with an AUC of 0.85. The optimal sRAGE cut-off value for malnutrition risk was 1362.5 pg/ml.</div></div><div><h3>Conclusions</h3><div>Higher sRAGE levels were prospectively associated with poorer nutritional outcomes in older adults, particularly in women. sRAGE may aid early identification of inflammation-related malnutrition risk.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"214 ","pages":"Article 113032"},"PeriodicalIF":4.3,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145961037","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}

引用次数: 0

Irisin and the muscle–brain axis: Mechanisms and translational potential 鸢尾素和肌肉-脑轴：机制和转化潜力

IF 4.3

Experimental gerontology

Pub Date : 2026-01-09 DOI: 10.1016/j.exger.2026.113028

Beatrice Arosio , Anna Picca

The muscle–brain axis integrates peripheral metabolic activity with central nervous system function. Among the endocrine signaling molecules regulating such crosstalk, the peptide hormone irisin released during muscle contraction seems to play relevant roles. Irisin is generated by the proteolytic cleavage of the fibronectin type III domain-containing protein 5 and has emerged as a key regulator of neurotrophic and metabolic adaptation. Although initially described as a myokine, irisin is also expressed in adipose and neural tissues, acting through autocrine, paracrine, and endocrine mechanisms. Irisin binds to the αV/β5 integrin receptor complex and activates a network of signaling pathways which promote mitochondrial biogenesis, autophagy, oxidative stress resistance, and modulation of inflammatory responses. Within the central nervous system, irisin induces brain-derived neurotrophic factor expression and contributes to synaptic plasticity, neurogenesis, and cognitive preservation. Experimental models show that irisin reduces amyloid burden, limits α-synuclein pathology, suppresses neuroinflammation, and stabilizes blood–brain barrier integrity, supporting a disease-modifying role in neurodegenerative conditions. In skeletal muscle, irisin stimulates myogenesis, enhances anabolic signaling, and improves metabolic efficiency, suggesting broader relevance for sarcopenia and age-related metabolic decline. Herein, we discuss irisin as a promising biomarker and a candidate therapeutic target for disorders characterized by concurrent muscle deterioration and cognitive impairment.

肌脑轴整合了外周代谢活动和中枢神经系统功能。在调节这种串扰的内分泌信号分子中，肌肉收缩时释放的肽激素鸢尾素似乎起着相关的作用。鸢尾素是由含有纤维连接蛋白III型结构域的蛋白5的蛋白水解裂解产生的，并已成为神经营养和代谢适应的关键调节剂。虽然最初被描述为一种肌肉因子，但鸢尾素也在脂肪和神经组织中表达，通过自分泌、旁分泌和内分泌机制起作用。鸢尾素与αV/β5整合素受体复合物结合，激活一系列信号通路，促进线粒体生物发生、自噬、氧化应激抵抗和炎症反应调节。在中枢神经系统中，鸢尾素诱导脑源性神经营养因子表达，有助于突触可塑性、神经发生和认知保存。实验模型表明，鸢尾素可减轻淀粉样蛋白负担，限制α-突触核蛋白病理，抑制神经炎症，稳定血脑屏障完整性，支持在神经退行性疾病中的疾病调节作用。在骨骼肌中，鸢尾素刺激肌肉生成，增强合成代谢信号，提高代谢效率，这表明鸢尾素与肌肉减少症和年龄相关的代谢下降有广泛的相关性。在此，我们讨论鸢尾素作为一种有前景的生物标志物和以并发肌肉退化和认知障碍为特征的疾病的候选治疗靶点。

{"title":"Irisin and the muscle–brain axis: Mechanisms and translational potential","authors":"Beatrice Arosio , Anna Picca","doi":"10.1016/j.exger.2026.113028","DOIUrl":"10.1016/j.exger.2026.113028","url":null,"abstract":"<div><div>The muscle–brain axis integrates peripheral metabolic activity with central nervous system function. Among the endocrine signaling molecules regulating such crosstalk, the peptide hormone irisin released during muscle contraction seems to play relevant roles. Irisin is generated by the proteolytic cleavage of the fibronectin type III domain-containing protein 5 and has emerged as a key regulator of neurotrophic and metabolic adaptation. Although initially described as a myokine, irisin is also expressed in adipose and neural tissues, acting through autocrine, paracrine, and endocrine mechanisms. Irisin binds to the αV/β5 integrin receptor complex and activates a network of signaling pathways which promote mitochondrial biogenesis, autophagy, oxidative stress resistance, and modulation of inflammatory responses. Within the central nervous system, irisin induces brain-derived neurotrophic factor expression and contributes to synaptic plasticity, neurogenesis, and cognitive preservation. Experimental models show that irisin reduces amyloid burden, limits α-synuclein pathology, suppresses neuroinflammation, and stabilizes blood–brain barrier integrity, supporting a disease-modifying role in neurodegenerative conditions. In skeletal muscle, irisin stimulates myogenesis, enhances anabolic signaling, and improves metabolic efficiency, suggesting broader relevance for sarcopenia and age-related metabolic decline. Herein, we discuss irisin as a promising biomarker and a candidate therapeutic target for disorders characterized by concurrent muscle deterioration and cognitive impairment.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"214 ","pages":"Article 113028"},"PeriodicalIF":4.3,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145928645","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}

引用次数: 0