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CRISPR-Cas9 mediated d3GHR knockout in HEK293 cells: Revealing the longevity associated isoform stress resilience HEK293 细胞中 CRISPR-Cas9 介导的 d3GHR 基因敲除:揭示与长寿相关的同工酶应激恢复能力。
IF 3.9 Pub Date : 2024-09-23 DOI: 10.1016/j.exger.2024.112586
Ghadeer Falah , Lital Sharvit , Gil Atzmon
The Growth Hormone Receptor (GHR) gene encodes a protein that is essential for mediating the biological effects of growth hormone (GH). A series of molecular events are set off when GH binds to its receptor, resulting in a variety of physiological reactions linked to development, growth, and metabolism. Recently a particular genetic variation, within the GHR gene that is labeled as the “d3GHR,” which lacks exon 3 was associated with longevity. This specific deletion isoform was connected to changes in the structure of the GHR protein, which may have an impact on the GHR's function. To test in vitro the advantage of the d3 carrier that may link to longevity, we employed the CRISPR/Cas9 technique to produce two isoforms: the homozygotes isoform (d3/d3) and the heterozygotes isoform (d3/fl) using HEK293 cell line. The CRISPR editing effectiveness was >85 %, indicating that we had successfully built the Cas9-gRNA complex that is appropriate for the GHR gene. The viability of the resulted isoform cells was examined under three environmental stressors that mimic some aging processes. In addition, we examined the GHR signaling pathway by selecting potential downstream genes in the GHR signaling cascade. The results show that heterozygotes cells demonstrated higher survival rates under UV radiation compared with the WT cells (87 % compared with 67 % for the WT cells when exposed to 2 min of UV radiation), and in fasting conditions, the d3GHR cells showed a 15 % greater viability than the WT cells. Moreover, the baseline expression levels (without intervention) of the IGF1 and JAK/STAT genes signaling pathways significantly declined in the homozygotes cells compared with the WT (p < 0.05). This noteworthy finding might offer a practical approach to test illness prevention and give the scientific community critical new insights on mechanism associated with lifespan.
生长激素受体(GHR)基因编码一种对介导生长激素(GH)的生物效应至关重要的蛋白质。当 GH 与其受体结合时,会引发一系列分子事件,导致与发育、生长和新陈代谢有关的各种生理反应。最近,GHR 基因中一种被称为 "d3GHR "的特殊基因变异与长寿有关,这种变异缺少第 3 号外显子。这种特定的缺失异构体与 GHR 蛋白结构的变化有关,可能会对 GHR 的功能产生影响。为了在体外测试可能与长寿有关的d3载体的优势,我们采用CRISPR/Cas9技术,利用HEK293细胞系产生了两种异构体:同基因异构体(d3/d3)和杂合子异构体(d3/fl)。CRISPR编辑的有效性大于85%,表明我们成功构建了适合GHR基因的Cas9-gRNA复合物。我们在三种模拟衰老过程的环境压力下检测了所得到的异构体细胞的存活率。此外,我们还通过选择 GHR 信号级联中潜在的下游基因,研究了 GHR 信号通路。结果显示,与 WT 细胞相比,杂合子细胞在紫外线辐射下的存活率更高(在紫外线辐射 2 分钟时,WT 细胞的存活率为 87%,杂合子细胞为 67%);在禁食条件下,d3GHR 细胞的存活率比 WT 细胞高 15%。此外,与 WT 细胞相比,同卵双生细胞中 IGF1 和 JAK/STAT 基因信号通路的基线表达水平(无干预)显著下降(p
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引用次数: 0
Association between C-reactive protein, Life's Essential 8, and mortality in American adults: Insights from NHANES 2005–2010 data analysis 美国成年人 C 反应蛋白、生命必需 8 项指标与死亡率之间的关系:NHANES 2005-2010 年数据分析的启示。
IF 3.9 Pub Date : 2024-09-21 DOI: 10.1016/j.exger.2024.112590
Xin Li, Yongxin Zhu, Tingting Yan, Jie Fang, Xin Xu, Xiaodong Xu

Objective

To evaluate the independent, mediating, interactive, and associated effects of C-reactive protein (CRP) and Life's Essential 8 (LE8) on all-cause and cardiovascular mortality.

Methods

Utilizing data from 10,043 participants in the NHANES 2005–2010, we employed Cox proportional hazards regression models and causal mediation analysis to investigate the joint and interactive effects of Life's Essential 8 (LE8) and C-reactive protein (CRP) on mortality risk.

Results

During an average follow-up of 137.10 months, there were 1591 all-cause deaths and 485 cardiovascular deaths. Weighted linear regression showed that for patients with low cardiovascular health (CVH), the adjusted β was −0.22 (95 % CI: −0.27 to −0.17) for moderate cardiovascular health (CVH) and -0.36 (95 % CI: −0.43 to −0.30) for high cardiovascular health (CVH). Mediation analysis revealed that C-reactive protein (CRP) mediated 10.43 % of all-cause mortality and 9.20 % of cardiovascular mortality for moderate cardiovascular health (CVH) compared to low cardiovascular health (CVH), and 9.95 % and 8.32 % respectively for high cardiovascular health (CVH) compared to low cardiovascular health (CVH). No significant multiplicative or additive interactions between Life's Essential 8 (LE8) and C-reactive protein (CRP) were found in all-cause mortality or cardiovascular mortality. Individuals with high cardiovascular health (CVH) and the first quartile of C-reactive protein (CRP) had HRs of 0.30 (95 % CI 0.18–0.48) for all-cause mortality and 0.31 (95 % CI 0.13–0.74) for cardiovascular mortality compared to those with low cardiovascular health (CVH) and the fourth quartile of C-reactive protein (CRP).

Conclusion

These findings suggest that CRP could significantly influence the relationship between cardiovascular health (CVH) and mortality. Interventions that target both lifestyle factors and CRP levels may improve cardiovascular health and potentially lower mortality risks.
目的:评估 C 反应蛋白(CRP)和生命之本 8(LE8)对全因和心血管死亡率的独立、中介、交互和相关影响:评估 C 反应蛋白(CRP)和生命之本 8(LE8)对全因死亡率和心血管死亡率的独立、中介、交互和相关影响:利用 2005-2010 年国家健康调查(NHANES)中 10,043 名参与者的数据,我们采用 Cox 比例危险回归模型和因果中介分析来研究生命必需 8(LE8)和 C 反应蛋白(CRP)对死亡风险的联合和交互影响:在平均 137.10 个月的随访期间,共有 1591 例全因死亡和 485 例心血管疾病死亡。加权线性回归显示,对于心血管健康程度低(CVH)的患者,心血管健康程度中等(CVH)的调整后β值为-0.22(95 % CI:-0.27至-0.17),心血管健康程度高(CVH)的调整后β值为-0.36(95 % CI:-0.43至-0.30)。中介分析显示,与低心血管健康水平(CVH)相比,中度心血管健康水平(CVH)的C反应蛋白(CRP)介导了10.43%的全因死亡率和9.20%的心血管死亡率;与低心血管健康水平(CVH)相比,高度心血管健康水平(CVH)的C反应蛋白(CRP)介导了9.95%的全因死亡率和8.32%的心血管死亡率。在全因死亡率或心血管死亡率方面,未发现生命基本指标 8(LE8)与 C 反应蛋白(CRP)之间存在明显的乘法或加法交互作用。与心血管健康水平低(CVH)和C反应蛋白(CRP)处于第一四分位数的人相比,心血管健康水平高(CVH)和C反应蛋白(CRP)处于第一四分位数的人的全因死亡率HR值为0.30(95 % CI 0.18-0.48),心血管死亡率HR值为0.31(95 % CI 0.13-0.74):这些研究结果表明,CRP 可显著影响心血管健康(CVH)与死亡率之间的关系。针对生活方式因素和 CRP 水平的干预措施可改善心血管健康,并有可能降低死亡风险。
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引用次数: 0
Employ machine learning to identify NAD+ metabolism-related diagnostic markers for ischemic stroke and develop a diagnostic model 利用机器学习识别缺血性中风的 NAD+ 代谢相关诊断标记,并开发诊断模型
IF 3.9 Pub Date : 2024-09-19 DOI: 10.1016/j.exger.2024.112584
Yameng Sun , Shenghao Ding , Fei Shen , Xiaolan Yang , Wenhua Sun , Jieqing Wan

Ischemic stroke (IS) is a severe condition regulated by complex molecular alterations. This study aimed to identify potential nicotinamide adenine dinucleotide (NAD+) metabolism-associated diagnostic markers of IS and explore their associations with immune dynamics. Weighted Gene Co-expression Network Analysis and single-sample gene set enrichment analysis (ssGSEA) were employed to identify key gene modules on the GEO dataset (GSE16561). LASSO regression was used to identify diagnostic genes. A diagnostic model was then developed using the training dataset, and its performance was assessed using a validation dataset (GSE22255 dataset). Associations between hub genes and immune cells, immune response genes, and human leukocyte antigen (HLA) genes were assessed by ssGSEA. A regulatory network was constructed using mirBase and TRRUST databases. A total of 20 NAD+ metabolic genes exhibited noteworthy expression variations. Within the module notably associated with NAD+ metabolism, 19 specific genes were included in the diagnostic model, which was validated on the GSE22255 dataset (AUC: 0.733). There were significant disparities in immune cell populations, immune response genes, and HLA gene expression, all of which were associated with the hub genes. A regulatory network composed of 153 edges and 103 nodes was constructed. This study advances our understanding of IS by providing insights into NAD+ metabolism and gene interactions, contributing to potential diagnostic innovations in IS.

缺血性中风(IS)是一种受复杂分子变化调控的严重疾病。本研究旨在确定潜在的烟酰胺腺嘌呤二核苷酸(NAD+)代谢相关的IS诊断标记物,并探讨它们与免疫动态的关系。研究人员采用加权基因共表达网络分析和单样本基因组富集分析(ssGSEA)来识别GEO数据集(GSE16561)中的关键基因模块。LASSO 回归用于识别诊断基因。然后利用训练数据集建立诊断模型,并利用验证数据集(GSE22255 数据集)评估其性能。ssGSEA评估了中枢基因与免疫细胞、免疫反应基因和人类白细胞抗原(HLA)基因之间的关联。利用 mirBase 和 TRRUST 数据库构建了调控网络。共有 20 个 NAD+ 代谢基因表现出值得注意的表达变化。在与 NAD+ 代谢显著相关的模块中,19 个特定基因被纳入诊断模型,该模型在 GSE22255 数据集上得到了验证(AUC:0.733)。免疫细胞群、免疫反应基因和 HLA 基因表达存在明显差异,所有这些都与中枢基因有关。由 153 条边缘和 103 个节点组成的调控网络得以构建。这项研究通过对 NAD+ 代谢和基因相互作用的深入研究,增进了我们对 IS 的了解,从而为 IS 的潜在诊断创新做出了贡献。
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引用次数: 0
Increased knee-extension strength and steps per day after a novel post-hospitalization rehabilitative program in older adults (65+): Secondary analyses of a randomized controlled single-blinded trial using an expanded sample size 老年人(65 岁以上)出院后参加新型康复计划后,膝关节伸展力量和每天行走步数均有增加:使用扩大样本量对随机对照单盲试验进行二次分析
IF 3.9 Pub Date : 2024-09-17 DOI: 10.1016/j.exger.2024.112582
Mette Merete Pedersen , Helle Gybel Juul-Larsen , Rasmus Hoxer Brødsgaard , Baker Jawad , Jonathan F. Bean , Janne Petersen , Thomas Bandholm

Introduction

Older adults are at risk of developing new or worsened disability when hospitalized for acute medical illness. This study is a secondary analysis of the STAND-Cph trial on the effect of a simple strength training intervention initiated during hospitalization and continued after discharge. We investigated the between-group difference in change in functional performance outcomes, the characteristics of patients who experienced a relevant effect of the intervention, and the characteristics of those who were compliant with the intervention, using an expanded sample size as protocolized.

Methods

The STAND-Cph was a randomized controlled trial conducted at a major Danish university hospital. Acutely admitted older adult patients (65+) from the Emergency Department were randomized to the intervention group receiving progressive strength training and a protein supplement during and after hospitalization (12 sessions over 4 weeks) or control group receiving usual care. The primary outcome was the de Morton Mobility Index assessed at baseline and 4 weeks after discharge. The secondary outcomes were 24-h mobility (assessed by ActivPAL accelerometers), isometric knee-extension strength, 30 s. sit-to-stand performance, and habitual gait speed.

Results

Between September 2013 and September 2018, a total of 158 patients were included and randomized to either the intervention group (N = 80; mean age 79.9 ± 7.6 years) or the control group (N = 78; mean age 80.8 ± 7.4 years). We found no significant between-group difference in change in our primary outcome (p > 0.05). Both the intention-to-treat (difference in change 0.14 Nm/kg (95 % CI 0.03;0.24), p = 0.01) and the per protocol (difference in change 0.16 Nm/kg (95 % CI 0.04;0.29), p = 0.008) analyses showed that between baseline and 4 weeks, knee-extension strength increased significantly more in the intervention group than in the control group. Also, the per protocol analysis showed that the intervention group increased their daily number of steps significantly more than the control group (difference in change 1088 steps (95 % CI 44; 2132); p = 0.04). When examining subgroups of patients, we found no significant differences neither between those who experienced a clinically relevant improvement in the de Morton Mobility Index and those who did not, nor between those who were compliant and those who were not.

Conclusion

This exploratory analysis indicates that while simple progressive strength training and protein supplementation does not improve functional performance assessed by the de Morton Mobility Index, it can benefit specific facets of physical activity and muscle strength among geriatric patients.

导言:老年人因急性内科疾病住院时有可能出现新的残疾或残疾恶化。本研究是对 STAND-Cph 试验的二次分析,研究对象是住院期间开始并在出院后继续进行简单力量训练干预的效果。我们调查了功能表现结果变化的组间差异、经历过相关干预效果的患者的特征以及坚持干预的患者的特征,并按照协议扩大了样本量。方法 STAND-Cph 是一项随机对照试验,在丹麦一家大型大学医院进行。急诊科急诊入院的老年患者(65 岁以上)被随机分为干预组和对照组,干预组在住院期间和住院后接受渐进式力量训练和蛋白质补充剂(4 周 12 次训练),对照组接受常规护理。主要结果是在基线和出院后 4 周评估 de Morton 活动指数。次要结果为24小时活动能力(由ActivPAL加速度计评估)、等长膝关节伸展力量、30秒坐立表现和习惯步速。结果在2013年9月至2018年9月期间,共纳入158名患者,并随机分配到干预组(N = 80;平均年龄(79.9 ± 7.6)岁)或对照组(N = 78;平均年龄(80.8 ± 7.4)岁)。我们发现,在主要结果的变化方面,组间差异并不明显(p > 0.05)。意向治疗分析(变化差值为 0.14 牛米/公斤(95 % CI 0.03;0.24),p = 0.01)和按方案分析(变化差值为 0.16 牛米/公斤(95 % CI 0.04;0.29),p = 0.008)均显示,从基线到 4 周期间,干预组的膝关节伸展力量明显高于对照组。此外,按方案分析表明,干预组每天增加的步数明显多于对照组(变化差异为 1088 步 (95 % CI 44; 2132); p = 0.04)。结论这项探索性分析表明,虽然简单的渐进式力量训练和蛋白质补充并不能改善以德莫顿活动指数评估的功能表现,但却能使老年患者的身体活动和肌肉力量的特定方面受益。
{"title":"Increased knee-extension strength and steps per day after a novel post-hospitalization rehabilitative program in older adults (65+): Secondary analyses of a randomized controlled single-blinded trial using an expanded sample size","authors":"Mette Merete Pedersen ,&nbsp;Helle Gybel Juul-Larsen ,&nbsp;Rasmus Hoxer Brødsgaard ,&nbsp;Baker Jawad ,&nbsp;Jonathan F. Bean ,&nbsp;Janne Petersen ,&nbsp;Thomas Bandholm","doi":"10.1016/j.exger.2024.112582","DOIUrl":"10.1016/j.exger.2024.112582","url":null,"abstract":"<div><h3>Introduction</h3><p>Older adults are at risk of developing new or worsened disability when hospitalized for acute medical illness. This study is a secondary analysis of the STAND-Cph trial on the effect of a simple strength training intervention initiated during hospitalization and continued after discharge. We investigated the between-group difference in change in functional performance outcomes, the characteristics of patients who experienced a relevant effect of the intervention, and the characteristics of those who were compliant with the intervention, using an expanded sample size as protocolized.</p></div><div><h3>Methods</h3><p>The STAND-Cph was a randomized controlled trial conducted at a major Danish university hospital. Acutely admitted older adult patients (65+) from the Emergency Department were randomized to the intervention group receiving progressive strength training and a protein supplement during and after hospitalization (12 sessions over 4 weeks) or control group receiving usual care. The primary outcome was the de Morton Mobility Index assessed at baseline and 4 weeks after discharge. The secondary outcomes were 24-h mobility (assessed by ActivPAL accelerometers), isometric knee-extension strength, 30 s. sit-to-stand performance, and habitual gait speed.</p></div><div><h3>Results</h3><p>Between September 2013 and September 2018, a total of 158 patients were included and randomized to either the intervention group (N = 80; mean age 79.9 ± 7.6 years) or the control group (N = 78; mean age 80.8 ± 7.4 years). We found no significant between-group difference in change in our primary outcome (<em>p</em> &gt; 0.05). Both the intention-to-treat (difference in change 0.14 Nm/kg (95 % CI 0.03;0.24), <em>p</em> = 0.01) and the per protocol (difference in change 0.16 Nm/kg (95 % CI 0.04;0.29), <em>p</em> = 0.008) analyses showed that between baseline and 4 weeks, knee-extension strength increased significantly more in the intervention group than in the control group. Also, the per protocol analysis showed that the intervention group increased their daily number of steps significantly more than the control group (difference in change 1088 steps (95 % CI 44; 2132); <em>p</em> = 0.04). When examining subgroups of patients, we found no significant differences neither between those who experienced a clinically relevant improvement in the de Morton Mobility Index and those who did not, nor between those who were compliant and those who were not.</p></div><div><h3>Conclusion</h3><p>This exploratory analysis indicates that while simple progressive strength training and protein supplementation does not improve functional performance assessed by the de Morton Mobility Index, it can benefit specific facets of physical activity and muscle strength among geriatric patients.</p></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"196 ","pages":"Article 112582"},"PeriodicalIF":3.9,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0531556524002286/pdfft?md5=aafb116ca8ae806718c27d158982ace1&pid=1-s2.0-S0531556524002286-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142242698","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}
引用次数: 0
Changes in primitive reflexes in older adults and their relationship to mental health indices: An experimental investigation 老年人原始反射的变化及其与心理健康指数的关系:实验研究
IF 3.9 Pub Date : 2024-09-16 DOI: 10.1016/j.exger.2024.112583
Erzsébet Stephens-Sarlós, Eliza Toth, Ferenc Ihász, Zoltán Alföldi, Angéla Somogyi, Attila Szabo

The reemergence of primitive reflexes (PRs) in older age is related to cognitive impairment. Currently, there are no means to prevent or slow their reappearance, but research evidence exists for their control in children. Therefore, this experiment investigated whether a 16-week special sensorimotor exercise program could benefit older adults and whether the intervention-induced changes (if any) may be associated with various indices of mental health. Of 115 adults over 60, 95 completed the study (mean age = 76.37 ± SD = 7.04 years, 22 % men). The experimental group (n = 38) showed an almost threefold decline in PRs compared to controls. In contrast, the control group (n = 57) exhibited a nearly threefold increase in PRs compared to the intervention group. Cognitive function increased in the experimental but not in the control group. Changes in PRs over the 16-week intervention were positively related to negative mental health indices (hopelessness and perceived stress) and negatively related to well-being. These findings suggest that the here-presented mild sensorimotor exercises could affect older adults' reemerging PRs and that changes in PRs are associated with mental health benefits. These results may open new research avenues toward preventing cognitive and psychological decline in older adults.

老年人原始反射(PRs)的重新出现与认知障碍有关。目前,还没有任何方法可以预防或减缓原始反射的再次出现,但有研究证据表明儿童可以控制原始反射。因此,本实验研究了为期 16 周的特殊感觉运动锻炼计划是否能使老年人受益,以及干预引起的变化(如果有的话)是否与各种心理健康指数相关。在 115 名 60 岁以上的成年人中,95 人完成了研究(平均年龄 = 76.37 ± SD = 7.04 岁,22% 为男性)。与对照组相比,实验组(n = 38)的 PR 值下降了近三倍。相比之下,对照组(n = 57)的 PR 值比干预组增加了近三倍。实验组的认知功能有所提高,而对照组则没有。在为期 16 周的干预过程中,PRs 的变化与消极心理健康指数(无望感和感知压力)呈正相关,而与幸福感呈负相关。这些研究结果表明,这里介绍的轻度感官运动锻炼可以影响老年人的再发PRs,而PRs的变化与心理健康的益处相关。这些结果可能会为预防老年人认知和心理衰退开辟新的研究途径。
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引用次数: 0
Exploring the impact of lighting sources on walking behavior in obstructed walkways among older adults 探究照明光源对老年人在有障碍的人行道上行走行为的影响
IF 3.9 Pub Date : 2024-09-14 DOI: 10.1016/j.exger.2024.112580
Yue Luo , Yuhao Chen , Gaojian Huang , Boyi Hu

The pandemic has reinforced older adults' reliance on their homes and the concept of “aging in place”. Changes like reduced physical strength and cognitive deficit, however, have heightened the challenge of simple tasks like obstacle crossing among older adults, let alone when older adults cannot perceive the surroundings well during the nighttime. The study is, therefore, to evaluate the impact of lighting on older adults' obstacle-crossing behavior during the nighttime. Twenty-seven older adults (81 ± 6 yrs., 171 ± 12 cm, 75 ± 20 kg, 14 females) were recruited. Participants were asked to cross over the obstacle in a dark residential environment under point or line light. We found that the line light tended to (1) induce more external rotation of the trailing hip (p = 0.037) and more internal rotation of the leading ankle (p < 0.001) at leading leg liftoff; and (2) result in a more upright and erect posture during stance phase (less hip flexion, p = 0.006) and swing phase of the trailing leg (reduced pelvic flexion, p = 0.038). Postural changes induced by line light demonstrated improved body control, highlighting the influence of spatial information (horizontal & vertical directions) on crossing behavior in dark environments. The findings can provide additional evidence for the design of light systems in both retirement communities and individual homes. This is particularly important when designing built environments for the aging population, in cases where the surroundings may pose challenges such as obstructed walking, and other complex floor conditions.

大流行病加强了老年人对家的依赖和 "居家养老 "的概念。然而,体力下降和认知缺陷等变化加剧了老年人跨越障碍等简单任务的挑战性,更不用说老年人在夜间无法很好地感知周围环境。因此,本研究旨在评估照明对老年人夜间跨越障碍行为的影响。研究招募了 27 名老年人(81 ± 6 岁,171 ± 12 厘米,75 ± 20 千克,14 名女性)。参与者被要求在黑暗的居住环境中,在点光源或线光源下跨越障碍物。我们发现,线光有以下倾向:(1) 在前腿抬起时,诱导后腿髋关节更多外旋(p = 0.037),前腿踝关节更多内旋(p < 0.001);(2) 在站立阶段(髋关节屈曲较少,p = 0.006)和后腿摆动阶段(骨盆屈曲减少,p = 0.038),导致姿势更加直立和挺拔。线光诱导的姿势变化改善了身体控制,突出了空间信息(水平方向和垂直方向)对黑暗环境中穿越行为的影响。这些发现为养老社区和个人住宅的照明系统设计提供了更多证据。在为老龄人口设计建筑环境时,这一点尤为重要,因为周围环境可能会带来一些挑战,如行走受阻和其他复杂的地面条件。
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引用次数: 0
Correlation between blood pressure and mortality in older critically ill patients: Insights from a large intensive care unit database 老年重症患者血压与死亡率之间的相关性:来自大型重症监护室数据库的启示。
IF 3.9 Pub Date : 2024-09-14 DOI: 10.1016/j.exger.2024.112573
Chong Zhang , Weiru Liang , Wei Su , Yi Chen , Tingting Guo , Kun Hu , Meng Ning , Yingwu Liu

Objectives

The study aimed to investigate the relationship between blood pressure (BP) levels and mortality among critically ill older adults in the intensive care unit (ICU), establish optimal BP target for this population, and assess the mediating effect of severe malnutrition on BP-related mortality.

Methods

Data were extracted from the Medical Information Mart for Intensive Care IV version 2.2 database, focusing on critically ill patients aged 80 years and older. The analysis included various BP parameters, such as systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP).

Results

The study cohort comprised 14,660 critically ill patients, of whom 1558 (10.6 %) experienced ICU mortality and 2493 (17.0 %) experienced in-hospital mortality. Lower BP levels (SBP ≤ 112 mmHg; DBP ≤ 53 mmHg; MAP ≤65 mmHg), were associated with an increased risk of both ICU and in-hospital mortality. Notably, only reduced SBP levels were linked to a higher risk of 1-year mortality, with an adjusted hazard ratio 1.13 (95 % confidence interval 1.05 to 1.23). Additionally, severe malnutrition was identified as a mediator in the relationship between low BP levels and ICU mortality, with BP levels positively correlated with prognostic nutritional indexes.

Conclusion

Among critically ill older adults, lower BP levels are significantly associated with higher risks of ICU and in-hospital mortality, while reduced SBP levels are linked to 1-year mortality. These findings emphasize the importance of assessing nutritional status in older ICU patients with low BP levels to potentially mitigate mortality risk.

研究目的该研究旨在调查重症监护室(ICU)中患重症的老年人的血压(BP)水平与死亡率之间的关系,为这一人群确定最佳血压目标,并评估严重营养不良对血压相关死亡率的中介作用:数据提取自重症监护医学信息市场 IV(MIMIC-IV)2.2 版数据库,主要针对 80 岁及以上的重症患者。分析包括各种血压参数,如收缩压(SBP)、舒张压(DBP)和平均动脉压(MAP):研究队列包括 14,660 名重症患者,其中 1558 人(10.6%)在重症监护室死亡,2493 人(17.0%)在院内死亡。较低的血压水平(SBP ≤ 112 mmHg; DBP ≤ 53 mmHg; MAP ≤ 65 mmHg)与重症监护室和院内死亡风险的增加有关。值得注意的是,只有 SBP 水平降低才与较高的 1 年死亡风险有关,调整后的危险比为 1.13(95 % 置信区间为 1.05 至 1.23)。此外,严重营养不良被认为是血压水平低与重症监护病房死亡率之间关系的中介因素,血压水平与预后营养指数呈正相关:结论:在重症老年人中,较低的血压水平与较高的重症监护室和院内死亡风险显著相关,而较低的血压水平与 1 年死亡率相关。这些发现强调了对血压水平较低的 ICU 老年患者进行营养状况评估以降低死亡风险的重要性。
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引用次数: 0
Association between single-point insulin sensitivity estimator and heart failure in older adults: A cross-sectional study 单点胰岛素敏感性估计值与老年人心力衰竭之间的关系:横断面研究
IF 3.9 Pub Date : 2024-09-11 DOI: 10.1016/j.exger.2024.112578
Xiao-Feng Zhu , Ye-Tong Mo , Yu-Qi Hu , Yu-Xue Feng , En-Hui Liu

Background

Heart failure (HF) is a condition caused by a malfunction of the heart's pumping function. The single-point insulin sensitivity estimator (SPISE) index is a novel indicator for assessing insulin resistance in humans. However, the connection between the SPISE index and the risk of HF in the elderly is unknown. Therefore, our study aims to evaluate the connection between the SPISE index and HF in older adults.

Methods

The study was based on data collected from the 1999–2020 National Health and Nutrition Examination Survey database and included 6165 participants aged ≥60 years. The multivariable linear regression model and the smooth fitting curve model were applied to investigate the connection between the SPISE index and HF in the elderly. Furthermore, the subgroup analysis was performed to investigate the interactive factors.

Results

In this study, the mean age of the population was 69.38 years. After adjusting for all covariates, we observed that the SPISE index was inversely related to the prevalence of HF (OR = 0.87, 95 % CI = 0.80–0.94, P < 0.001) in older adults. The interaction analysis showed that the association might be affected by diabetes mellitus and smoking status. Additionally, an inflection point between the SPISE index and HF was found among older women.

Conclusions

An inverse correlation was detected between the SPISE index and HF in the elderly. This could provide new insight into the prevention and management of HF in the elderly population.

背景:心力衰竭(HF)是一种由心脏泵血功能失常引起的疾病。单点胰岛素敏感性估计指数(SPISE)是评估人体胰岛素抵抗的新指标。然而,SPISE 指数与老年人罹患高血压风险之间的关系尚不清楚。因此,我们的研究旨在评估 SPISE 指数与老年人心房颤动之间的联系:研究基于 1999-2020 年全国健康与营养调查数据库收集的数据,纳入了 6165 名年龄≥60 岁的参与者。应用多变量线性回归模型和平滑拟合曲线模型研究老年人 SPISE 指数与心房颤动之间的关系。此外,还进行了亚组分析以研究交互因素:本研究中,研究对象的平均年龄为 69.38 岁。在对所有协变量进行调整后,我们发现 SPISE 指数与心房颤动的患病率成反比(OR = 0.87,95 % CI = 0.80-0.94,P 结论:SPISE 指数与心房颤动的患病率成反比:在老年人中,SPISE指数与心房颤动之间存在反相关性。这为预防和管理老年人高血压提供了新的思路。
{"title":"Association between single-point insulin sensitivity estimator and heart failure in older adults: A cross-sectional study","authors":"Xiao-Feng Zhu ,&nbsp;Ye-Tong Mo ,&nbsp;Yu-Qi Hu ,&nbsp;Yu-Xue Feng ,&nbsp;En-Hui Liu","doi":"10.1016/j.exger.2024.112578","DOIUrl":"10.1016/j.exger.2024.112578","url":null,"abstract":"<div><h3>Background</h3><p>Heart failure (HF) is a condition caused by a malfunction of the heart's pumping function. The single-point insulin sensitivity estimator (SPISE) index is a novel indicator for assessing insulin resistance in humans. However, the connection between the SPISE index and the risk of HF in the elderly is unknown. Therefore, our study aims to evaluate the connection between the SPISE index and HF in older adults.</p></div><div><h3>Methods</h3><p>The study was based on data collected from the 1999–2020 National Health and Nutrition Examination Survey database and included 6165 participants aged ≥60 years. The multivariable linear regression model and the smooth fitting curve model were applied to investigate the connection between the SPISE index and HF in the elderly. Furthermore, the subgroup analysis was performed to investigate the interactive factors.</p></div><div><h3>Results</h3><p>In this study, the mean age of the population was 69.38 years. After adjusting for all covariates, we observed that the SPISE index was inversely related to the prevalence of HF (OR = 0.87, 95 % CI = 0.80–0.94, <em>P</em> &lt; 0.001) in older adults. The interaction analysis showed that the association might be affected by diabetes mellitus and smoking status. Additionally, an inflection point between the SPISE index and HF was found among older women.</p></div><div><h3>Conclusions</h3><p>An inverse correlation was detected between the SPISE index and HF in the elderly. This could provide new insight into the prevention and management of HF in the elderly population.</p></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"196 ","pages":"Article 112578"},"PeriodicalIF":3.9,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0531556524002249/pdfft?md5=76ec7c587ba37df09e3ccc2fdbacc53a&pid=1-s2.0-S0531556524002249-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142157041","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}
引用次数: 0
The effect of physical exercise on circulating neurotrophic factors in healthy aged subjects: A meta-analysis and meta-regression 体育锻炼对健康老年人循环神经营养因子的影响:荟萃分析和荟萃回归
IF 3.9 Pub Date : 2024-09-11 DOI: 10.1016/j.exger.2024.112579
Samira Behrad , Seyed Ashkan Tabibzadeh Dezfuli , Reza Yazdani , Saeed Hayati , Sanaz Mirzayan Shanjani

Vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), and insulin-like growth factor-1 (IGF-1) may help the brain resist both functional and structural neurodegeneration, which is critical for maintaining cognitive and neurological health in older adults. This meta-analysis and meta-regression seek to elucidate the impact of physical activity on these biomarker levels in healthy seniors, as well as to examine the influence of several moderator factors, including age, sex, period length, and time, for the first time. The standardized mean effect metric was used to assess the influence of weights, which reflected each group's relative importance in comparison to baseline data. The study looked at potential moderating factors including age, gender, and physical activity levels. The analysis of 11 studies indicated no significant effect of physical activity on VEGF levels [0.328, CI 95 % (−0.871 to 1.52); I2 = 0.00; p = 0.592; Q = 4.14]. Physical activity had a substantial impact on brain-derived neurotrophic factor (0.827, 95 % confidence interval: 0.487 to 1.16; I2 = 0.00; p = 0.00; Q = 78.46), with females showing particularly notable effects (Tau2 = 0.327, Tau = 0.571, I2 = 80.90 %, Q = 68.05, df = 15, p = 0.00). Physical activity also had a substantial effect on insulin-like growth factor 1 (0.276, 95 % confidence interval: 0.065 to 0.487; I2 = 0.00; p = 0.10; Q = 8.35), indicating that it positively influences IGF-1 levels. Overall, while physical exercise has a significant effect on BDNF and IGF-1, more research is needed to fully understand its impact on vascular endothelial growth factor and to investigate how individual characteristics may influence exercise outcomes.

血管内皮生长因子(VEGF)、脑源性神经营养因子(BDNF)和胰岛素样生长因子-1(IGF-1)可帮助大脑抵抗功能性和结构性神经变性,这对维持老年人的认知和神经健康至关重要。这项荟萃分析和荟萃回归试图阐明体育锻炼对健康老年人这些生物标志物水平的影响,并首次研究了一些调节因素的影响,包括年龄、性别、周期长度和时间。标准化平均效应指标用于评估权重的影响,权重反映了与基线数据相比各组的相对重要性。研究考察了潜在的调节因素,包括年龄、性别和体育锻炼水平。对 11 项研究的分析表明,体育锻炼对血管内皮生长因子水平没有显著影响[0.328,CI 95 % (-0.871 to 1.52);I2 = 0.00;p = 0.592;Q = 4.14]。体育锻炼对脑源性神经营养因子有显著影响(0.827,95 % 置信区间:0.487 至 1.16;I2 = 0.00;p = 0.00;Q = 78.46),女性的影响尤为明显(Tau2 = 0.327,Tau = 0.571,I2 = 80.90 %,Q = 68.05,df = 15,p = 0.00)。体育锻炼对胰岛素样生长因子 1 也有很大影响(0.276,95% 置信区间:0.065 至 0.487;I2 = 0.00;P = 0.10;Q = 8.35),表明体育锻炼对 IGF-1 水平有积极影响。总之,虽然体育锻炼对BDNF和IGF-1有显著影响,但要充分了解体育锻炼对血管内皮生长因子的影响,并研究个体特征如何影响锻炼结果,还需要更多的研究。
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引用次数: 0
18F-Fluorodeoxyglucose positron emission tomography/computed tomography imaging reveals the protective effect of docosahexaenoic acid on glucose metabolism by reducing brain 27-hydroxycholesterol 18F-氟脱氧葡萄糖正电子发射断层扫描/计算机断层扫描成像显示了二十二碳六烯酸通过降低大脑 27-羟基胆固醇对葡萄糖代谢的保护作用。
IF 3.9 Pub Date : 2024-09-10 DOI: 10.1016/j.exger.2024.112577
Dalong Zhang , Zehao Wang , Shuangshuang Guo , Yue Sun , Dezheng Zhou , Wen Li , Jing Yan , Yongjie Chen , Suhui Luo , Guowei Huang , Zhiyong Qian , Zhenshu Li

Total cholesterol (TC) and the cholesterol oxidation product 27-hydroxycholesterol (27-OHC) are both increased in the elderly. Accumulating evidence has linked 27-OHC to glucose metabolism in the brain, while docosahexaenoic acid (DHA) has been shown to positively regulate the 27-OHC levels. However, it is unclear whether DHA may affect glucose metabolism in the brain by regulating 27-OHC levels. In this study, we hypothesized that DHA supplementation would modulate TC levels and reduce 27-OHC levels, thereby improving brain glucose metabolism in SAMP8 mice. The mice were assigned into the Control group and DHA dietary supplementation group. The study evaluated cholesterol levels, 27-OHC levels, and glucose metabolism in the brain. The results showed that DHA supplementation decreased serum levels of TC, low-density lipoprotein cholesterol (LDL-C), and increased levels of high-density lipoprotein cholesterol (HDL-C); and improved the glucose-corrected standardized uptake value of cortex, hippocampus, and whole brain regions in SAMP8 mice. In conclusion, supplementation of DHA could regulate the cholesterol composition and reduce the level of 27-OHC, thereby improving brain glucose metabolism in SAMP8 mice.

老年人的总胆固醇(TC)和胆固醇氧化产物 27-羟基胆固醇(27-OHC)都会升高。越来越多的证据表明,27-OHC 与大脑中的葡萄糖代谢有关,而二十二碳六烯酸(DHA)已被证明能积极调节 27-OHC 的水平。然而,目前还不清楚 DHA 是否会通过调节 27-OHC 水平来影响大脑中的葡萄糖代谢。在本研究中,我们假设补充 DHA 会调节 TC 水平并降低 27-OHC 水平,从而改善 SAMP8 小鼠的脑糖代谢。小鼠被分为对照组和 DHA 膳食补充剂组。研究评估了胆固醇水平、27-OHC 水平和大脑中的葡萄糖代谢。结果显示,补充 DHA 能降低 SAMP8 小鼠血清中胆固醇、低密度脂蛋白胆固醇(LDL-C)的水平,提高高密度脂蛋白胆固醇(HDL-C)的水平,并能改善大脑皮层、海马和整个脑区的葡萄糖校正标准化摄取值。总之,补充 DHA 可以调节胆固醇组成,降低 27-OHC 水平,从而改善 SAMP8 小鼠的脑糖代谢。
{"title":"18F-Fluorodeoxyglucose positron emission tomography/computed tomography imaging reveals the protective effect of docosahexaenoic acid on glucose metabolism by reducing brain 27-hydroxycholesterol","authors":"Dalong Zhang ,&nbsp;Zehao Wang ,&nbsp;Shuangshuang Guo ,&nbsp;Yue Sun ,&nbsp;Dezheng Zhou ,&nbsp;Wen Li ,&nbsp;Jing Yan ,&nbsp;Yongjie Chen ,&nbsp;Suhui Luo ,&nbsp;Guowei Huang ,&nbsp;Zhiyong Qian ,&nbsp;Zhenshu Li","doi":"10.1016/j.exger.2024.112577","DOIUrl":"10.1016/j.exger.2024.112577","url":null,"abstract":"<div><p>Total cholesterol (TC) and the cholesterol oxidation product 27-hydroxycholesterol (27-OHC) are both increased in the elderly. Accumulating evidence has linked 27-OHC to glucose metabolism in the brain, while docosahexaenoic acid (DHA) has been shown to positively regulate the 27-OHC levels. However, it is unclear whether DHA may affect glucose metabolism in the brain by regulating 27-OHC levels. In this study, we hypothesized that DHA supplementation would modulate TC levels and reduce 27-OHC levels, thereby improving brain glucose metabolism in SAMP8 mice. The mice were assigned into the Control group and DHA dietary supplementation group. The study evaluated cholesterol levels, 27-OHC levels, and glucose metabolism in the brain. The results showed that DHA supplementation decreased serum levels of TC, low-density lipoprotein cholesterol (LDL-C), and increased levels of high-density lipoprotein cholesterol (HDL-C); and improved the glucose-corrected standardized uptake value of cortex, hippocampus, and whole brain regions in SAMP8 mice. In conclusion, supplementation of DHA could regulate the cholesterol composition and reduce the level of 27-OHC, thereby improving brain glucose metabolism in SAMP8 mice.</p></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"196 ","pages":"Article 112577"},"PeriodicalIF":3.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0531556524002237/pdfft?md5=9e5d94c7e358ff164a13cd36aa5e52f5&pid=1-s2.0-S0531556524002237-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142147175","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}
引用次数: 0
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Experimental gerontology
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