体弱老年患者外周血单核细胞的线粒体功能。

IF 3.9

Experimental gerontology Pub Date : 2024-10-01 DOI:10.1016/j.exger.2024.112594

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

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引用次数: 0

摘要

背景：虚弱会增加老年综合症的发病率，甚至增加老年人的死亡风险。然而，由于病理过程复杂、临床表现多样，虚弱的诊断标准并不一致。为了确定有效的生物标志物，及早识别虚弱状态，我们研究了人外周血单核细胞（PBMCs）线粒体形态和功能与老年人虚弱状态的相关性：这项横断面研究对南京医科大学第一附属医院的393名受试者（年龄在25-100岁之间，女性占31.04%）进行了跟踪调查。受试者的虚弱状况由体力虚弱表型量表（PFP）进行评估。我们分析了线粒体的功能，包括线粒体拷贝数（mtDNAcn）、线粒体动力学相关基因丝裂蛋白1（MFN1）、丝裂蛋白2（MFN2）、视神经萎缩蛋白-1（OPA1）、裂变蛋白-1（FIS1）和达因明相关蛋白1（DRP1）的mRNA表达、线粒体氧化呼吸和活性氧（ROS）水平。透射电子显微镜（TEM）观察了线粒体的形态、大小和数量：在对性别和体重指数进行调整后，mtDNAcn、FIS1 的 mRNA 表达、线粒体呼吸功能（质子泄漏、最大耗氧量和呼吸储备）和 ROS 水平与年龄显著相关（P = 0.031、0.030、0.042、0.003、0.002、0.022）。校正年龄、性别和体重指数后，mtDNAcn和OPA1的mRNA表达分别与4米步速相关（P = 0.003，0.028）。与非体弱者相比，体弱老年人的 mtDNAcn、MFN1 的 mRNA 表达、线粒体基础呼吸、质子泄漏、最大耗氧量、ATP 产量和空间容量均显著下降（P = 0.013、0.036、0.026、0.024、0.012、0.029、0.032、0.020，分别为 0.013、0.036、0.026、0.024、0.012、0.029、0.032、0.020）。体弱组的 ROS 水平明显升高（P = 0.016）。与非体弱者相比，体弱组线粒体的数量、长度、周长和面积在 TEM 下均有所减少（均为 P 结论：体弱组线粒体的数量、长度、周长和面积均比非体弱组减少（均为 P）：线粒体功能障碍（mtDNAcn减少、线粒体形态受损、线粒体动态失衡、线粒体呼吸功能受损和ROS水平升高）与体弱状态显著相关。

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The mitochondrial function of peripheral blood mononuclear cells in frail older patients

Background

Frailty increases the incidence of geriatric syndromes and even the risk of death in old adults. However, the diagnostic criteria for frailty are inconsistent because of complex pathological processes and diverse clinical manifestations. To determine the effective biomarker and recognize frail status early, we investigated the correlation of mitochondrial morphology and function of human peripheral blood mononuclear cells (PBMCs) with frailty status in older adults.

Methods

This Cross-sectional study followed 393 participants (aged 25–100 years, female 31.04 %) from the First Affiliated Hospital of Nanjing Medical University. The frailty status of subjects was assessed by the physical frailty phenotype (PFP) scale. We analyzed mitochondria functions including mitochondria copy number (mtDNAcn), the mRNA expressions of mitochondrial dynamics-related genes mitofusin 1(MFN1), mitofusin 2(MFN2), optic atrophy protein-1(OPA1), fission protein-1(FIS1) and dynamin-related protein 1(DRP1), mitochondrial oxidative respiration and reactive oxygen species(ROS) levels in PBMCs. Mitochondria morphology, size, and number were observed by transmission electron microscopy (TEM).

Results

After adjustment for sex and BMI, mtDNAcn, the mRNA expression of FIS1, mitochondrial respiratory function (proton leak, maximum oxygen consumption, and respiratory reserve) and ROS level were significantly correlated with age (P = 0.031, 0.030, 0.042, 0.003, 0.002, 0.022, respectively). After correcting for age, sex, and BMI, mtDNAcn and the mRNA expression of OPA1 were correlated with 4 m gait speed respectively (P = 0.003, 0.028, respectively). Compared with non-frail people, mtDNAcn, the mRNA expression of MFN1, mitochondrial basal respiration, proton leak, maximum oxygen consumption, ATP production and space capacity were significantly decreased in frail older adults (P = 0.013, 0.036, 0.026, 0.024, 0.012, 0.032, 0.020, respectively). ROS levels were significantly increased in the frail group (P = 0.016). Compared with non-frail people, the number, length, and perimeter, area of mitochondria were reduced in frail group under TEM (all P < 0.001).

Conclusion

Mitochondrial dysfunctions (decreased mtDNAcn, impaired mitochondrial morphology, imbalanced mitochondrial dynamic, impaired mitochondrial respiratory function, and increased ROS levels) were significantly correlated with frail status.

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来源期刊

Experimental gerontology Ageing, Biochemistry, Geriatrics and Gerontology

CiteScore

6.70

自引率

0.00%

发文量

审稿时长

66 days