cognitive aging

认知衰老
  • 文章类型: Journal Article
    健康的生活方式可能是预防或至少延迟痴呆发作的重要先决条件。然而,大量不从事身体活动的成年人强调,需要制定和评估旨在提高坚持身体活动生活方式的干预方法.在这方面,混合体能训练,它通常结合了中心和家庭为基础的体育锻炼课程,并且在康复环境中被证明是成功的,可以提供一种有希望的方法来保护老年人的认知健康。尽管有潜力,这一领域的研究是有限的,因为混合体能训练干预措施在促进健康认知衰老方面未得到充分利用。此外,对于混合体能训练干预措施,缺乏普遍接受的定义或分类框架,这对未来在这一方向上的进展构成了挑战.为了解决这个差距,本文通过提供不同类型的定义和分类方法,向读者介绍混合体能训练,讨论它们的具体优点和缺点,并为未来的研究提供建议。具体来说,我们专注于应用数字技术来提供基于家庭的练习,因为它们的使用具有接触服务不足和边缘化群体的巨大潜力,例如生活在农村地区的行动不便的老年人。
    A healthy lifestyle can be an important prerequisite to prevent or at least delay the onset of dementia. However, the large number of physically inactive adults underscores the need for developing and evaluating intervention approaches aimed at improving adherence to a physically active lifestyle. In this regard, hybrid physical training, which usually combines center- and home-based physical exercise sessions and has proven successful in rehabilitative settings, could offer a promising approach to preserving cognitive health in the aging population. Despite its potential, research in this area is limited as hybrid physical training interventions have been underused in promoting healthy cognitive aging. Furthermore, the absence of a universally accepted definition or a classification framework for hybrid physical training interventions poses a challenge to future progress in this direction. To address this gap, this article informs the reader about hybrid physical training by providing a definition and classification approach of different types, discussing their specific advantages and disadvantages, and offering recommendations for future research. Specifically, we focus on applying digital technologies to deliver home-based exercises, as their use holds significant potential for reaching underserved and marginalized groups, such as older adults with mobility impairments living in rural areas.
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  • 文章类型: Journal Article
    由于人口老龄化,认知能力下降和痴呆的患病率将大幅增加。身体活动和久坐行为已被确定为与这些认知状况相关的可改变的生活方式行为。因此,这种文献计量分析的目的是揭示体育活动领域的知识结构,久坐的行为,2004年至2024年老年人的认知功能,并预测新出现的研究趋势。从WebofScienceCoreCollection检索到总共1,290种出版物。应用CiteSpace和VOSviewer进行性能分析,科学制图,和浓缩。T.Liu-Ambrose是最多产的作者(39种出版物),不列颠哥伦比亚大学是最多产的机构(48种出版物)。美国,中国,加拿大和加拿大是三个生产率最高的国家,分别有392、174和136种出版物。两个研究趋势揭示了该领域的知识结构,包括从评估干预措施对认知功能的有效性转变为评估干预措施对其他健康相关结果的有效性,以及关于身体活动和久坐行为在健康老龄化背景下的作用的研究的扩展。Sleep,久坐的行为,和虚拟现实可能是新兴的研究趋势,并可能预测未来的研究方向。总的来说,此文献计量分析为研究人员和其他利益相关者提供了该领域知识结构的一步概述,为今后的研究提供参考。
    Because of population ageing, there will be a vast increase in the prevalence of cognitive decline and dementia. Physical activity and sedentary behaviour have been identified as modifiable lifestyle behaviours associated with these cognitive conditions. Therefore, the aim of this bibliometric analysis is to reveal the knowledge structure of the field of physical activity, sedentary behaviour, and cognitive function among older adults from 2004 to 2024, and to predict emerging research trends. A total of 1290 publications were retrieved from the Web of Science Core Collection. CiteSpace and VOSviewer were applied to conduct performance analysis, science mapping, and enrichment. T. Liu-Ambrose was the most prolific author (39 publications), and the University of British Columbia was the most prolific institution (48 publications). The USA, China, and Canada were the three most productive countries with 392, 174, and 136 publications respectively. Two research trends revealed the knowledge structure of this field, including the shift from evaluating the effectiveness of interventions on cognitive function to evaluating the effectiveness of interventions on other health-related outcomes, as well as an expansion of research on the role of physical activity and sedentary behaviour in the context of healthy ageing. Sleep, sedentary behaviour, and virtual reality may be emerging research trends and may predict directions for future research. Collectively, this bibliometric analysis provides a one-step overview of the knowledge structure in this field for researchers and other stakeholders, as well as a reference for future research.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    背景:这项研究旨在评估计算机化认知训练(CCT)对白质(WM)神经可塑性和神经心理学表现的有效性。
    方法:共招募128名社区老年人(64.36±6.14岁),并随机分配到干预组或对照组。干预组的参与者接受了以家庭为基础的,多域,和30分钟的自适应CCT,一周两天,一年。神经心理学评估,弥散MRI,和T1加权结构MRI在干预前后进行.
    结果:128名参与者中有81名(干预组41名,对照组40名)完成了为期一年的干预,其中61例(干预组27例,对照组34例)接受了两次MRI扫描。在排除减员偏差之后,在Stroop颜色词测试(SCWT)(F=51.85,p<.001)上发现了显着的分组时间相互作用,干预组有所改善,对照组下降。在大脑层面,干预组左后丘脑辐射的轴向扩散率增加,这种增加与SCWT反应时间的减少显着相关(r=0.42,p=0.029)。对于灰质体积,没有发现明显的逐组时间相互作用。
    结论:我们的研究结果表明,进行多域自适应CCT是一种有效且可行的方法来抵消老年人的认知能力下降,WM神经可塑性支持认知改善。这项研究有助于了解CCT对老年人有益作用的神经基础。
    BACKGROUND: This study aims to evaluate the effectiveness of computerized cognitive training (CCT) on white matter (WM) neuroplasticity and neuropsychological performance.
    METHODS: A total of 128 community older adults (64.36 ± 6.14 years) were recruited and randomly assigned to the intervention or control group. Participants in the intervention group received a home-based, multidomain, and adaptive CCT for 30 minutes, 2 days per week for 1 year. Neuropsychological assessments, diffusion magnetic resonance imaging (MRI), and T1-weighted structural MRI were performed at the pre- and post-intervention visits.
    RESULTS: Eighty-one of 128 participants (41 in the intervention group and 40 in the control group) completed the 1-year intervention, and 61 of them (27 in the intervention group and 34 in the control group) underwent MRI scans twice. After excluding attrition bias, a significant time-by-group interaction on the Stroop Color-Word Test (SCWT; F = 51.85, p < .001) was found, showing improvement in the intervention group and a decline in the control group. At the brain level, the intervention group exhibited increased axial diffusivity in the left posterior thalamic radiation, and this increase was significantly correlated with reduced SCWT reaction time (r = ‒0.42, p = .029). No significant time-by-group interactions were found for gray matter volume.
    CONCLUSIONS: Our findings suggest that conducting multidomain adaptive CCT is an effective and feasible method to counteract cognitive decline in older adults, with WM neuroplasticity underpinning cognitive improvements. This study contributes to the understanding of the neural basis for the beneficial effect of CCT for older adults.
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  • 文章类型: Journal Article
    背景:尽管越来越多的证据表明,长期接触细颗粒物(PM2.5)与认知障碍有独立的联系,其成分的影响仍不清楚。本研究旨在探讨长期暴露于环境PM2.5成分混合物与中国老年人认知障碍的关系。并进一步确定主要贡献者。
    方法:中国纵向健康长寿研究(CLHLS)招募了15,274名≥65岁的成年人,并在2000-2018年期间进行了7次随访。环境PM2.5及其成分的浓度(即,黑碳[BC],有机质[OM],铵[NH4+],硫酸盐[SO42-],和硝酸盐[NO3-])是通过卫星检索和机器学习模型估计的。基于分位数的g计算模型用于评估5种PM2.5成分混合物的联合作用及其对认知障碍的相对贡献。按年龄组分层分析,性别,住宅(城市与农村),和地区(北部与南部)是为了识别弱势群体。
    结果:在平均3.03次随访(89,296.9人年)中,4294名(28.1%)参与者出现认知障碍。混合物暴露于5种PM2.5成分的每四分位数增加,认知障碍的校正风险比[HR](95%置信区间[CI])为1.08(1.05-1.11)。在qg计算模型中,BC在正方向上保持最大的指标权重(0.69),其次是OM(0.31)。亚组分析表明,年轻的老年人和农村居民之间的关联更强。
    结论:长期暴露于环境PM2.5,特别是其成分BC和OM,与中国老年人认知障碍发病风险升高相关。
    BACKGROUND: Although growing evidence has shown independent links of long-term exposure to fine particulate matter (PM2.5) with cognitive impairment, the effects of its constituents remain unclear. This study aims to explore the associations of long-term exposure to ambient PM2.5 constituents\' mixture with cognitive impairment in Chinese older adults, and to further identify the main contributor.
    METHODS: 15,274 adults ≥ 65 years old were recruited by the Chinese Longitudinal Healthy Longevity Study (CLHLS) and followed up through 7 waves during 2000-2018. Concentrations of ambient PM2.5 and its constituents (i.e., black carbon [BC], organic matter [OM], ammonium [NH4+], sulfate [SO42-], and nitrate [NO3-]) were estimated by satellite retrievals and machine learning models. Quantile-based g-computation model was employed to assess the joint effects of a mixture of 5 PM2.5 constituents and their relative contributions to cognitive impairment. Analyses stratified by age group, sex, residence (urban vs. rural), and region (north vs. south) were performed to identify vulnerable populations.
    RESULTS: During the average 3.03 follow-up visits (89,296.9 person-years), 4294 (28.1%) participants had developed cognitive impairment. The adjusted hazard ratio [HR] (95% confidence interval [CI]) for cognitive impairment for every quartile increase in mixture exposure to 5 PM2.5 constituents was 1.08 (1.05-1.11). BC held the largest index weight (0.69) in the positive direction in the qg-computation model, followed by OM (0.31). Subgroup analyses suggested stronger associations in younger old adults and rural residents.
    CONCLUSIONS: Long-term exposure to ambient PM2.5, particularly its constituents BC and OM, is associated with an elevated risk of cognitive impairment onset among Chinese older adults.
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  • 文章类型: Journal Article
    海马网络支持多种认知功能,在病理性认知衰老(PCA)及其相关疾病中可能具有生物学作用和功能。没有被探索过。在目前的研究中,共有116名老年人和39名正常对照(NC)(平均年龄:52.3±13.64岁;16名女性),39名轻度认知障碍(MCI)(平均年龄:68.15±9.28岁,14名女性),和38痴呆症(平均年龄:73.82±8.06岁,包括8名女性)。使用T1w/T2w比率和区域灰质组织概率图,通过微结构相似性网络方法评估海马内亚场和皮质-海马回路,分别。进行协方差分析以确定海马子场之间结构相似性的组间差异。进行了部分相关分析,以将三组的微观结构相似性的变化与认知表现相关联,控制年龄的影响,性别,教育,和脑小血管疾病。与NC相比,在轻度认知障碍(MCI)和痴呆患者中,观察到左CA3和左下膜之间的T1w/T2w比值相似性改变。左侧CA3是与认知能力下降相关的最受损区域。使用这些区域作为海马子场和皮质区域之间的转基因相似性比较的种子,组差异主要在左下膜和几个皮质区域之间观察到。通过利用T1w/T2w比率作为髓鞘含量的替代量度,我们的数据表明,海马CA3中突触重量的不平衡为解释PCA中海马神经元异常放电特征提供了基础.此外,我们的工作描述了正常和病理性认知老化的特定脑结构特征,并提示了认知老化异质性的潜在机制.
    The hippocampal networks support multiple cognitive functions and may have biological roles and functions in pathological cognitive aging (PCA) and its associated diseases, which have not been explored. In the current study, a total of 116 older adults with 39 normal controls (NC) (mean age: 52.3 ± 13.64 years; 16 females), 39 mild cognitive impairment (MCI) (mean age: 68.15 ± 9.28 years, 14 females), and 38 dementia (mean age: 73.82 ± 8.06 years, 8 females) were included. The within-hippocampal subfields and the cortico-hippocampal circuits were assessed via a micro-structural similarity network approach using T1w/T2w ratio and regional gray matter tissue probability maps, respectively. An analysis of covariance was conducted to identify between-group differences in structural similarities among hippocampal subfields. The partial correlation analyses were performed to associate changes in micro-structural similarities with cognitive performance in the three groups, controlling the effect of age, sex, education, and cerebral small-vessel disease. Compared with the NC, an altered T1w/T2w ratio similarity between left CA3 and left subiculum was observed in the mild cognitive impairment (MCI) and dementia. The left CA3 was the most impaired region correlated with deteriorated cognitive performance. Using these regions as seeds for GM similarity comparisons between hippocampal subfields and cortical regions, group differences were observed primarily between the left subiculum and several cortical regions. By utilizing T1w/T2w ratio as a proxy measure for myelin content, our data suggest that the imbalanced synaptic weights within hippocampal CA3 provide a substrate to explain the abnormal firing characteristics of hippocampal neurons in PCA. Furthermore, our work depicts specific brain structural characteristics of normal and pathological cognitive aging and suggests a potential mechanism for cognitive aging heterogeneity.
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  • 文章类型: Journal Article
    在认知科学领域,“成功的认知老化”现象是个体表现出超过年龄匹配者的认知能力的标志。然而,最重要的是强调当前研究中的重大差距,其特点是缺乏全面的调查,这些调查部署了大量的样本量来有条不紊地调查支撑这种认知成功的大脑生物标志物和贡献因素。正是在这种背景下,我们的研究应运而生,利用来自英国生物银行的数据。在这项研究中,我们从更大的17,072名受试者中精心策划了一个由1060名65岁及65岁以上个体组成的高度选择性队列.选择过程以他们惊人的认知弹性为指导,通过严格的评估确定,包括通用和特定的认知评估,与同龄阶层的同龄人相比。值得注意的是,所选参与者的认知能力与中年人通常观察到的认知敏锐度密切相关。我们的研究利用了一系列全面的神经影像学衍生指标,从三次特斯拉MRI扫描中获得(T1加权图像,dMRI,和静息状态功能磁共振成像)。这些指标包括解决灰质形态的图像衍生表型(IDP),大脑网络连接的力量,和白质的微结构属性。采用方差分析进行统计分析,Mann-WhitneyU测试,和卡方检验,以评估与成功认知衰老领域相关的国内流离失所者的独特方面。此外,这些分析旨在阐明在整个衰老过程中维持认知敏锐度的生活方式。我们的发现揭示了增强的认知能力与大脑中白质结构的完整性之间的强大而令人信服的关联。此外,表现出成功的认知衰老的个体在负责听觉感知的大脑区域表现出显著增强的活动,自愿运动控制,内存保留,和情绪调节。这些有利的认知属性反映在被调查队列的健康相关生活方式选择中,以提高教育水平为特征,较低的吸烟率,和适度饮酒的嗜好。此外,他们表现出优越的抓地力和提高步行速度。总的来说,这些发现为成功认知衰老的多方面决定因素提供了有价值的见解,包括神经生物学成分和生活方式。这种全面的理解大大有助于更广泛的关于衰老的论述,从而为制定旨在促进老龄人口认知福祉的有针对性的干预措施奠定了坚实的基础。
    In the realm of cognitive science, the phenomenon of \"successful cognitive aging\" stands as a hallmark of individuals who exhibit cognitive abilities surpassing those of their age-matched counterparts. However, it is paramount to underscore a significant gap in the current research, which is marked by a paucity of comprehensive inquiries that deploy substantial sample sizes to methodically investigate the cerebral biomarkers and contributory elements underpinning this cognitive success. It is within this context that our present study emerges, harnessing data derived from the UK Biobank. In this study, a highly selective cohort of 1060 individuals aged 65 and above was meticulously curated from a larger pool of 17,072 subjects. The selection process was guided by their striking cognitive resilience, ascertained via rigorous evaluation encompassing both generic and specific cognitive assessments, compared to their peers within the same age stratum. Notably, the cognitive abilities of the chosen participants closely aligned with the cognitive acumen commonly observed in middle-aged individuals. Our study leveraged a comprehensive array of neuroimaging-derived metrics, obtained from three Tesla MRI scans (T1-weighted images, dMRI, and resting-state fMRI). The metrics included image-derived phenotypes (IDPs) that addressed grey matter morphology, the strength of brain network connectivity, and the microstructural attributes of white matter. Statistical analyses were performed employing ANOVA, Mann-Whitney U tests, and chi-square tests to evaluate the distinctive aspects of IDPs pertinent to the domain of successful cognitive aging. Furthermore, these analyses aimed to elucidate lifestyle practices that potentially underpin the maintenance of cognitive acumen throughout the aging process. Our findings unveiled a robust and compelling association between heightened cognitive aptitude and the integrity of white matter structures within the brain. Furthermore, individuals who exhibited successful cognitive aging demonstrated markedly enhanced activity in the cerebral regions responsible for auditory perception, voluntary motor control, memory retention, and emotional regulation. These advantageous cognitive attributes were mirrored in the health-related lifestyle choices of the surveyed cohort, characterized by elevated educational attainment, a lower incidence of smoking, and a penchant for moderate alcohol consumption. Moreover, they displayed superior grip strength and enhanced walking speeds. Collectively, these findings furnish valuable insights into the multifaceted determinants of successful cognitive aging, encompassing both neurobiological constituents and lifestyle practices. Such comprehensive comprehension significantly contributes to the broader discourse on aging, thereby establishing a solid foundation for the formulation of targeted interventions aimed at fostering cognitive well-being among aging populations.
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  • 文章类型: Journal Article
    白天小睡的复杂关联,生物衰老和认知功能仍然没有定论。我们旨在评估白天午睡和两种衰老指标与认知的横截面和纵向关联,并检查午睡是否会通过更高级的衰老状态影响认知。
    数据来自中国健康与退休纵向研究。午睡是自我报告的。我们计算了两个已发表的生物衰老指标:Klemera和Doubal生物年龄(KDM-BA)和生理失调(PD),从临床生物标志物中获得信息。在每个波时计算认知z得分。线性混合模型用于探索午睡之间的纵向关联,两项老化措施,和认知能力下降。进行中介分析以评估生物学年龄加速对午睡和认知之间关联的中介作用。
    45岁以上的参与者被纳入分析。与中度午睡者(30-90分钟/小睡)相比,非午睡者的KDM-BA和PD更大[LS均值(LSM)=0.255,p=0.007;LSM=0.085,p=0.011]和更快的认知下降(LSM=-0.061,p=0.005)。KDM-BA(β=-0.007,p=0.018)和PD(β=-0.034,p<0.001)与总体认知z评分呈负相关。KDM-BA和PD部分介导了午睡对认知的影响。
    在中国中老年人中,与适度的午睡者相比,非午睡者似乎经历了更高级的衰老状态和认知能力下降的增加。衰老状态可能介导午睡与认知之间的关联。适度的午睡在促进健康老龄化和减轻中国中老年人认知能力下降的负担方面显示出希望。
    The complicated association of daytime napping, biological aging and cognitive function remains inconclusive. We aimed to evaluate the cross-sectional and longitudinal associations of daytime napping and two aging measures with cognition and to examine whether napping affects cognition through a more advanced state of aging.
    Data was collected from the China Health and Retirement Longitudinal Study. Napping was self-reported. We calculated two published biological aging measures: Klemera and Doubal biological age (KDM-BA) and physiological dysregulation (PD), which derived information from clinical biomarkers. Cognitive z-scores were calculated at each wave. Linear mixed models were used to explore the longitudinal association between napping, two aging measures, and cognitive decline. Mediation analyses were performed to assess the mediating effects of biological age acceleration on the association between napping and cognition.
    Participants aged over 45 years were included in the analyses. Non-nappers had greater KDM-BA and PD [LS means (LSM) = 0.255, p = 0.007; LSM = 0.085, p = 0.011] and faster cognitive decline (LSM = -0.061, p = 0.005)compared to moderate nappers (30-90 min/nap). KDM-BA (β = -0.007, p = 0.018) and PD (β = -0.034, p < 0.001) showed a negative association with overall cognitive z scores. KDM-BA and PD partially mediated the effect of napping on cognition.
    In middle-aged and older Chinese, compared to moderate nappers, non-nappers seem to experience a more advanced state of aging and increased rates of cognitive decline. The aging status possibly mediates the association between napping and cognition. Moderate napping shows promise in promoting healthy aging and reducing the burden of cognitive decline in Chinese middle-aged and older adults.
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  • 文章类型: Journal Article
    工作记忆(WM)障碍在正常衰老中已得到很好的表征。各种研究都探讨了WM老化过程中区域活动或区域间连通性的变化。我们提出大脑活动和连通性会随着年龄的增长而独立改变并影响WM性能。在包括168名老年受试者(年龄55-86岁)的社区样本中,在功能磁共振成像期间,通过经典的N-back任务评估了WM。根据后台功能连接的基本原理,我们独立评估了与年龄相关的脑活动改变和基于种子的区域间连通性.分析显示,与年龄相关的下顶叶小叶(IPL)的阳性活动减少,腹前扣带回皮质(ACC)的阴性活动增加,局部功能失调伴随着它们与其他皮质区域的连通性的改变。重要的是,IPL和ACC中的区域活动障碍可以介导与年龄相关的对准确率和反应时间的影响,分别,这些影响通过增强其背景功能连通性进一步抵消。因此,我们声称年龄引起的区域活动和区域间连通性的变化是独立发生的,并导致了WM衰老的变化。我们的发现展示了大脑活动和功能连接在成年后期相互作用的方式,从而为理解WM和认知衰老提供了新的视角。
    Working memory (WM) impairment has been well characterized in normal aging. Various studies have explored changes in either the regional activity or the interregional connectivity underlying the aging process of WM. We proposed that brain activity and connectivity would independently alter with aging and affect WM performance. WM was assessed with a classical N-back task during functional magnetic resonance imaging in a community-based sample comprising 168 elderly subjects (aged 55-86 years old). Following the rationale of background functional connectivity, we assessed age-related alterations in brain activity and seed-based interregional connectivity independently. Analyses revealed age-related decrease in positive activity of the inferior parietal lobule (IPL) and an increase in the negative activity of the ventral anterior cingulate cortex (ACC), and the local functional dysfunctions were accompanied by alterations in their connectivity to other cortical regions. Importantly, regional activity impairments in the IPL and ACC could mediate age-related effects on accuracy rate and reaction time, respectively, and those effects were further counterbalanced by enhancement of their background functional connectivity. We thus claimed that age-induced alterations in regional activity and interregional connectivity occurred independently and contributed to WM changes in aging. Our findings presented the way brain activity and functional connectivity interact in the late adulthood, thus providing a new perspective for understanding WM and cognitive aging.
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  • 文章类型: Journal Article
    背景:大建中汤(DJZ)是中医治疗阳虚证的经典名方,记载于东汉朝的金奎要略。认知衰老可以表现出与阳虚的临床特征相似的线粒体能量缺乏特征。然而,对DJZ治疗对认知衰老中线粒体自噬的影响了解甚少。
    目的:这项工作的目的是破译DJZ对抗认知衰老的有效性和机制,专注于线粒体自噬。
    方法:YFP-ParkinHeLa细胞,D-半乳糖(D-gal)诱导小鼠(500mg/kg,持续35d,s.c.)和SH-SY5Y细胞(80mg/ml,持续6h)。首先,利用YFP-ParkinHeLa细胞中YFP-Parkinpuncta(一种众所周知的线粒体自噬标记)的形成来发现DJZ的线粒体自噬诱导。此外,在体内用DJZ处理后评估与PINK1/Parkin途径和线粒体功能相关的基因和蛋白(3.5g/kg或1.75g/kg,i.g,35d)和体外(0.2、2和20μg/ml,12h).此外,DJZ的有效性(3.5g/kg或1.75g/kg,在D-gal小鼠中测量用于减轻认知老化和神经损伤的i.g)。最后,siPINK1用于DJZ的体外反向验证。
    结果:DJZ以剂量依赖性方式显著诱导YFP-ParkinHeLa细胞中YFP-Parkin点的形成。DJZ治疗后D-gal小鼠Parkin免疫荧光强度和线粒体膜Parkin蛋白表达均显著升高。DJZ显著激活了D-gal诱导的小鼠和SH-SY5Y细胞中PINK1/Parkin通路的抑制作用。同时,DJZ明显逆转了D-gal诱导的线粒体功能损伤。此外,DJZ可显着改善D-gal小鼠的神经病理学损伤和认知能力下降。最后,PINK1在体外被siPINK1敲低后,DJZ的神经保护作用和DJZ的Parkin增强作用明显逆转。
    结论:我们的发现首先表明DJZ可以通过促进PINK1/Parkin介导的线粒体自噬来缓解认知老化,从而保护线粒体功能,表明DJZ可能被认为是认知衰老的有希望的干预措施。
    BACKGROUND: Dajianzhong decoction (DJZ) is a classical famous formula for treating yang-deficiency-syndrome in traditional Chinese medicine and recorded in Jin-Kui-Yao-Lue in Dynasty of Dong Han. Cognitive aging can present similar features of mitochondrial energy deficits to the clinical features of Yang deficiency. However, there is poor understanding of the effects of DJZ treatment on mitophagy in cognitive aging.
    OBJECTIVE: The aims of this work were to decipher the effectiveness and mechanism of DJZ against cognitive aging, focusing on mitophagy.
    METHODS: YFP-Parkin HeLa cells, D-galactose (D-gal) -induced mice (500 mg/kg for 35 d, s. c.) and SH-SY5Y cells (80 mg/ml for 6 h) were established. Firstly, the formation of YFP-Parkin puncta (a well-known mitophagy marker) in YFP-Parkin HeLa cells was employed to discover the mitophagy induction of DJZ. Moreover, the genes and proteins related to PINK1/Parkin pathway and mitochondrial functions were evaluated after treatment with DJZ in vivo (3.5 g/kg or 1.75 g/kg, i. g, 35 d) and in vitro (0.2, 2 and 20 μg/ml, 12 h). Furthermore, the effectiveness of DJZ (3.5 g/kg or 1.75 g/kg, i. g) for alleviating cognitive aging and nerve damage was measured in D-gal mice. Finally, siPINK1 was applied to reverse validation of DJZ in vitro.
    RESULTS: The formation of YFP-Parkin puncta in YFP-Parkin HeLa cells was markedly induced by DJZ in a dose-dependent manner. The immunofluorescence intensity of Parkin and the protein expression of Parkin in mitochondrial membrane in D-gal mice were significantly increased after treatment of DJZ. The inhibition of PINK1/Parkin pathway in D-gal-induced mice and SH-SY5Y cells was significantly activated by DJZ. Simultaneously, the impairment of mitochondrial functions induced by D-gal were markedly reversed by DJZ. In addition, DJZ significantly ameliorated the neuropathological injury and cognitive declines in D-gal mice. Finally, after PINK1 was knocked down by siPINK1 in vitro, the neuroprotective effects of DJZ and the Parkin enhancement effect of DJZ were markedly reversed.
    CONCLUSIONS: Our findings firstly showed DJZ could relieve cognitive aging through facilitating PINK1/Parkin-mediated mitophagy to protect against mitochondrial functions, indicating DJZ may be regarded as a promising intervention in cognitive aging.
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