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认知衰弱患者外周血细胞的线粒体功能

The mitochondrial function of peripheral blood cells in cognitive frailty patients.

作者信息

Qin Li, Huang Tingting, Zhang Danmei, Wei Liqin, Li Guochao, Zhu Qianqian, Tong Qiangwei, Ding Guoxian, Liu Juan

机构信息

Division of Geriatric Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

出版信息

Front Aging Neurosci. 2024 Dec 11;16:1503246. doi: 10.3389/fnagi.2024.1503246. eCollection 2024.

Abstract

BACKGROUND

Cognitive frailty (), characterized by the coexistence of physical frailty and cognitive impairment, is linked to increased morbidity and mortality in older adults. While has been linked to multiple physiological and lifestyle factors, the underlying biological mechanisms remain poorly understood. This study investigated the risk factors for and explored the relationship between mitochondrial function and in hospitalized patients.

METHODS

A total of 279 hospitalized individuals were recruited from December 2020 to August 2022, conducted comprehensive clinical assessments, and collected peripheral blood samples. was evaluated using the Physical Frailty Phenotype and Montreal Cognitive Assessment scales. Nutritional status was assessed with the Mini Nutritional Assessment, and depression was measured using the Geriatric Depression Scale. DNA was obtained from the peripheral blood and interrogated for mitochondrial DNA copy number (mtDNAcn). Peripheral blood mononuclear cells isolated from peripheral blood were examined for respiratory function and reactive oxygen species (ROS) levels. Additionally, plasma samples were analyzed for inflammatory markers and Carnitine Palmitoyltransferase II (CPT2).

RESULTS

Among the participants, 90 were classified as and 46 as non- Logistic regression analysis revealed that increased age (OR 1.156, 95% CI 1.064-1.255), lower educational attainment (OR 0.115, 95% CI 0.024-0.550), malnutrition (OR 0.713, 95% CI 0.522-0.973), and higher depression scores (OR 1.345, 95% CI 1.065-1.699) were significantly associated with The independent t tests and Mann-Whitney U tests showed the group exhibited impaired mitochondrial function, characterized by reduced mtDNAcn and respiratory activity, coupled with elevated ROS, interleukin-6, and CPT2 levels compared with the non- group. After adjusted for age, sex, and BMI, compared with non- group, the OR values for the group of mtDNAcn and ROS were 0.234 (95% CI = 0.065-0.849) ( = 0.027) and 1.203 (95% CI = 1.075-1.347) ( = 0.001), respectively. The Sensitive analysis showed that the area under curve values for mtDNAcn and ROS were 0.653 and 0.925.

CONCLUSION

Age, lower educational attainment, malnutrition, and depression are significant risk factors for CF. Moreover, mitochondrial dysfunction, characterized by decreased mtDNAcn, impaired respiratory function and increased ROS levels appears to be a critical phenotype of

摘要

背景

认知衰弱(CF)以身体衰弱和认知障碍并存为特征,与老年人发病率和死亡率增加有关。虽然CF与多种生理和生活方式因素有关,但其潜在的生物学机制仍知之甚少。本研究调查了住院患者CF的危险因素,并探讨了线粒体功能与CF之间的关系。

方法

2020年12月至2022年8月共招募了279名住院患者,进行了全面的临床评估,并采集了外周血样本。使用身体衰弱表型和蒙特利尔认知评估量表评估CF。用微型营养评定法评估营养状况,用老年抑郁量表测量抑郁情况。从外周血中获取DNA并检测线粒体DNA拷贝数(mtDNAcn)。检测从外周血中分离出的外周血单个核细胞的呼吸功能和活性氧(ROS)水平。此外,分析血浆样本中的炎症标志物和肉碱棕榈酰转移酶II(CPT2)。

结果

在参与者中,90人被归类为CF,46人被归类为非CF。逻辑回归分析显示,年龄增加(比值比[OR]1.·156,95%置信区间[CI]1.064-1.255)、教育程度较低(OR 0.115,95%CI 0.024-0.550)、营养不良(OR 0.713,95%CI 0.522-0.973)和抑郁评分较高(OR 1.345,95%CI 1.065-1.699)与CF显著相关。独立样本t检验和曼-惠特尼U检验显示,与非CF组相比,CF组线粒体功能受损,表现为mtDNAcn和呼吸活性降低,同时ROS、白细胞介素-6和CPT2水平升高。在调整年龄、性别和体重指数后,与非CF组相比,CF组mtDNAcn和ROS的OR值分别为0.234(95%CI=0.065-0.849)(P=0.027)和1.203(95%CI=1.075-1.347)(P=0.001)。敏感性分析显示,mtDNAcn和ROS的曲线下面积值分别为0.653和0.925。

结论

年龄、教育程度较低、营养不良和抑郁是CF的重要危险因素。此外,以mtDNAcn降低、呼吸功能受损和ROS水平升高为特征的线粒体功能障碍似乎是CF的关键表型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06f1/11669044/bd10f90d128e/fnagi-16-1503246-g001.jpg

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