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在老年人的外周血单核细胞中,观察到线粒体偶联效率提高,同时其他线粒体呼吸参数减少。

Increased Efficiency of Mitochondrial Coupling With a Reduction in Other Mitochondrial Respiratory Parameters in Peripheral Blood Mononuclear Cells Is Observed in Older Adults.

机构信息

Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.

Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand.

出版信息

J Gerontol A Biol Sci Med Sci. 2023 Mar 1;78(3):384-391. doi: 10.1093/gerona/glac201.

Abstract

Mitochondrial dysfunction is a factor potentially contributing to the Aging process. However, evidence surrounding changes in mitochondrial function and aging is still limited; therefore, this study aimed to investigate further the association between them. Possible confounding factors were included in the statistical analysis to explore the possibility of any independent associations. One thousand seven hundred and sixty-nine participants (619 middle-aged adults [age < 65] and 1,150 older adults [age ≥ 65]) from the Electricity Generating Authority of Thailand were enrolled in the study. The clinical characteristics and medical history were collected. Peripheral blood mononuclear cells (PBMCs) were isolated from venous blood and used for analysis of mitochondrial function. Several parameters pertinent to mitochondrial respiration including non-mitochondrial respiration, basal respiration, maximal respiration, proton leak, and spare respiratory capacity were found to be two to three times lower in the mitochondria isolated from the cells of older adults. Interestingly, the mitochondrial ATP production was only slightly reduced, and the percentage of coupling efficiency of PBMC mitochondria was significantly higher in the older adult group. The mitochondrial mass and oxidative stress were significantly reduced in older adult participants; however, the ratio of oxidative stress to mass was significantly increased. The association of these parameters with age was still shown to be the same from the outcome of the multivariate analyses. The mitochondrial functions and mitochondrial mass in PBMCs were shown to decline in association with age. However, the upregulation of mitochondrial oxidative stress production and mitochondrial coupling efficiency might indicate a compensatory response in mitochondria during aging.

摘要

线粒体功能障碍是导致衰老过程的一个因素。然而,关于线粒体功能变化与衰老之间的关系的证据仍然有限;因此,本研究旨在进一步探讨它们之间的联系。在统计分析中纳入了可能的混杂因素,以探讨任何独立关联的可能性。从泰国发电局招募了 1769 名参与者(619 名中年成年人[年龄<65]和 1150 名老年人[年龄≥65])参与了这项研究。收集了临床特征和病史。从静脉血中分离外周血单核细胞(PBMC),并用于分析线粒体功能。从老年人细胞中分离的线粒体中,有几个与线粒体呼吸相关的参数(包括非线粒体呼吸、基础呼吸、最大呼吸、质子泄漏和备用呼吸能力)发现低了两到三倍。有趣的是,线粒体 ATP 产生仅略有减少,并且老年人组的 PBMC 线粒体的偶联效率百分比显著更高。老年参与者的线粒体质量和氧化应激明显降低;然而,氧化应激与质量的比值显著增加。从多变量分析的结果来看,这些参数与年龄的关联仍然相同。PBMC 中的线粒体功能和线粒体质量与年龄呈下降趋势。然而,线粒体氧化应激产生和线粒体偶联效率的上调可能表明衰老过程中线粒体的代偿反应。

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