Relationship between Mitochondrial Quality Control Markers, Lower Extremity Tissue Composition, and Physical Performance in Physically Inactive Older Adults.
Relationship between Mitochondrial Quality Control Markers, Lower Extremity Tissue Composition, and Physical Performance in Physically Inactive Older Adults.
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DOI：
10.3390/cells12010183
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发表时间：
2023-01-02
期刊：
影响因子：
6
通讯作者：
Hood, David A. A.
中科院分区：
文献类型：
--
作者：
Picca, Anna;Triolo, Matthew;Wohlgemuth, Stephanie E. E.;Martenson, Matthew S. S.;Mankowski, Robert T. T.;Anton, Stephen D. D.;Marzetti, Emanuele;Leeuwenburgh, Christiaan;Hood, David A. A.
关键词：
肌肉中线粒体质量和功能的改变可能与年龄相关的身体功能下降有关。自噬-溶酶体系统是线粒体质量控制 (MQC) 的主要组成部分，其所发挥的作用尚不完全清楚。这项研究的目的是获得肌肉中自噬、线粒体自噬和溶酶体标志物之间关系的初步迹象，以及年轻人和老年人的身体机能和下肢组织成分的测量。共有 23 名参与者入组，其中 9 名年轻人（平均年龄：24.3 ± 4.3 岁）和 14 名老年人（平均年龄：77.9 ± 6.3 岁）。通过磁共振成像对下肢组织成分进行体积定量，并将组织成分指数计算为肌肉和肌间脂肪组织体积之间的比率。老年参与者的身体表现通过短期身体表现电池（SPPB）进行评估。通过蛋白质免疫印迹法在股外侧肌活检中测量自噬标记物 p62、线粒体自噬介质 BCL2/腺病毒 E1B 19 kDa 蛋白相互作用蛋白 3 (BNIP3)、溶酶体标记物转录因子 EB、空泡型 ATP 酶和溶酶体相关膜蛋白 1 的蛋白质水平。与年轻参与者相比，老年人的肌肉体积较小，组织成分指数较低。 p62 和 BNIP3 的蛋白质含量在老年人中较高。 p62和BNIP3与组织成分指数之间呈负相关。 p62 和 BNIP3 也与 SPPB 5 次坐站测试的表现有关。我们的结果表明，自噬/线粒体自噬-溶酶体系统标记物表达的改变与下肢组织成分的恶化和肌肉功能障碍有关。需要进行更多研究来阐明有缺陷的 MQC 在人类肌肉衰老中的作用，并确定药物开发的新生物靶点。
Altered mitochondrial quality and function in muscle may be involved in age-related physical function decline. The role played by the autophagy–lysosome system, a major component of mitochondrial quality control (MQC), is incompletely understood. This study was undertaken to obtain initial indications on the relationship between autophagy, mitophagy, and lysosomal markers in muscle and measures of physical performance and lower extremity tissue composition in young and older adults. Twenty-three participants were enrolled, nine young (mean age: 24.3 ± 4.3 years) and 14 older adults (mean age: 77.9 ± 6.3 years). Lower extremity tissue composition was quantified volumetrically by magnetic resonance imaging and a tissue composition index was calculated as the ratio between muscle and intermuscular adipose tissue volume. Physical performance in older participants was assessed via the Short Physical Performance Battery (SPPB). Protein levels of the autophagy marker p62, the mitophagy mediator BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), the lysosomal markers transcription factor EB, vacuolar-type ATPase, and lysosomal-associated membrane protein 1 were measured by Western immunoblotting in vastus lateralis muscle biopsies. Older adults had smaller muscle volume and lower tissue composition index than young participants. The protein content of p62 and BNIP3 was higher in older adults. A negative correlation was detected between p62 and BNIP3 and the tissue composition index. p62 and BNIP3 were also related to the performance on the 5-time sit-to-stand test of the SPPB. Our results suggest that an altered expression of markers of the autophagy/mitophagy–lysosomal system is related to deterioration of lower extremity tissue composition and muscle dysfunction. Additional studies are needed to clarify the role of defective MQC in human muscle aging and identify novel biological targets for drug development.
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