整体健康依赖于骨骼肌的特征,通常随着年龄的增长而下降,部分是由于与线粒体氧化还原失衡和生物能功能障碍相关的机制。以前,遗传上缺乏线粒体NAD(P)+转代酶(NNT,由烟酰胺核苷酸转氨酶基因编码),参与线粒体NADPH供应的酶,被证明表现出运动行为的缺陷。这里,通过使用年轻,中年,和老年NNT缺陷(Nnt-/-)小鼠和年龄匹配的对照(Nnt+/+),我们旨在研究NNT表达和衰老如何影响肌肉生物能量功能和运动性能。对小鼠进行挂线测试以评估运动性能,虽然线粒体生物能学是在比目鱼的纤维束中进行评估的,股外侧肌和足底肌。与年龄匹配的对照相比,在中年和老年Nnt-/-小鼠中观察到平均线挂评分的年龄相关降低。虽然比目鱼的呼吸频率,在年轻小鼠的基因型之间,股外侧肌和plant肌没有显着差异,中年和老年Nnt-/-小鼠的比目鱼肌和股外侧肌的耗氧率确实降低。值得注意的是,比目鱼,表现出最高的NNT表达水平,是受衰老影响最大的肌肉,NNT损失。此外,比目鱼纤维的组织学显示,老年Nnt-/-小鼠的集中核数量增加,表明形态异常。总之,我们的研究结果表明,NNT表达缺乏导致小鼠衰老过程中的运动损伤和肌肉功能障碍.
Overall health relies on features of skeletal muscle that generally decline with age, partly due to mechanisms associated with mitochondrial redox imbalance and bioenergetic dysfunction. Previously, aged mice genetically devoid of the mitochondrial NAD(P)+ transhydrogenase (NNT, encoded by the nicotinamide nucleotide transhydrogenase gene), an enzyme involved in mitochondrial NADPH supply, were shown to exhibit deficits in locomotor behavior. Here, by using young, middle-aged, and older NNT-deficient (Nnt-/-) mice and age-matched controls (Nnt+/+), we aimed to investigate how muscle bioenergetic function and motor performance are affected by NNT expression and aging. Mice were subjected to the wire-hang test to assess locomotor performance, while mitochondrial bioenergetics was evaluated in fiber bundles from the soleus, vastus lateralis and plantaris muscles. An age-related decrease in the average wire-hang score was observed in middle-aged and older Nnt-/- mice compared to age-matched controls. Although respiratory rates in the soleus, vastus lateralis and plantaris muscles did not significantly differ between the genotypes in young mice, the rates of oxygen consumption did decrease in the soleus and vastus lateralis muscles of middle-aged and older Nnt-/- mice. Notably, the soleus, which exhibited the highest NNT expression level, was the muscle most affected by aging, and NNT loss. Additionally, histology of the soleus fibers revealed increased numbers of centralized nuclei in older Nnt-/- mice, indicating abnormal morphology. In summary, our findings suggest that NNT expression deficiency causes locomotor impairments and muscle dysfunction during aging in mice.