Fišar Zdeněk, Hroudová Jana, Zvěřová Martina, Jirák Roman, Raboch Jiří, Kitzlerová Eva
Department of Psychiatry, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 11, 120 00 Prague, Czech Republic.
Biomedicines. 2023 May 28;11(6):1564. doi: 10.3390/biomedicines11061564.
Mitochondrial dysfunction is an important cellular hallmark of aging and neurodegeneration. Platelets are a useful model to study the systemic manifestations of mitochondrial dysfunction. To evaluate the age dependence of mitochondrial parameters, citrate synthase activity, respiratory chain complex activity, and oxygen consumption kinetics were assessed. The effect of cognitive impairment was examined by comparing the age dependence of mitochondrial parameters in healthy individuals and those with neuropsychiatric disease. The study found a significant negative slope of age-dependence for both the activity of individual mitochondrial enzymes (citrate synthase and complex II) and parameters of mitochondrial respiration in intact platelets (routine respiration, maximum capacity of electron transport system, and respiratory rate after complex I inhibition). However, there was no significant difference in the age-related changes of mitochondrial parameters between individuals with and without cognitive impairment. These findings highlight the potential of measuring mitochondrial respiration in intact platelets as a means to assess age-related mitochondrial dysfunction. The results indicate that drugs and interventions targeting mitochondrial respiration may have the potential to slow down or eliminate certain aging and neurodegenerative processes. Mitochondrial respiration in platelets holds promise as a biomarker of aging, irrespective of the degree of cognitive impairment.
线粒体功能障碍是衰老和神经退行性变的重要细胞特征。血小板是研究线粒体功能障碍全身表现的有用模型。为评估线粒体参数的年龄依赖性,对柠檬酸合酶活性、呼吸链复合体活性和氧消耗动力学进行了评估。通过比较健康个体和神经精神疾病患者线粒体参数的年龄依赖性,研究了认知障碍的影响。该研究发现,完整血小板中单个线粒体酶(柠檬酸合酶和复合体II)的活性以及线粒体呼吸参数(常规呼吸、电子传递系统的最大能力和复合体I抑制后的呼吸速率)的年龄依赖性均有显著的负斜率。然而,有认知障碍和无认知障碍个体之间线粒体参数的年龄相关变化并无显著差异。这些发现凸显了测量完整血小板中线粒体呼吸作为评估年龄相关线粒体功能障碍手段的潜力。结果表明,针对线粒体呼吸的药物和干预措施可能有潜力减缓或消除某些衰老和神经退行性过程。无论认知障碍程度如何,血小板中的线粒体呼吸有望成为衰老的生物标志物。