Nakahara H, Kanno T, Inai Y, Utsumi K, Hiramatsu M, Mori A, Packer L
Institute of Medical Science, Center for Adult Diseases, Kuraashiki, Japan.
Free Radic Biol Med. 1998 Jan 1;24(1):85-92. doi: 10.1016/s0891-5849(97)00164-0.
Oxidative damage to DNA, proteins, and lipids in mitochondria caused by free radicals may be one factor in aging. Oxidative phosphorylation was estimated in liver mitochondria from senescence accelerated mice (SAMP8) and a senescence resistant substrain (SAMR1). The respiratory control ratio decreased in liver mitochondria of SAMP8 during aging, and it was estimated that at 18 months of age this respiratory control value suggested that it might be insufficient to provide ATP synthesis necessary for normal cell metabolism. In addition, the ADP/O, an index of efficiency of ATP synthesis, was depressed at 18 months of age. Dinitrophenol-dependent uncoupled respiration in liver mitochondria of SAMP8 mice was markedly decreased with aging, suggesting a dysfunctional energy transfer mechanism in mitochondria of aged SAMP8 mice. Active uptake of calcium in liver mitochondria was markedly dysfunctional in SAMP8 mice with aging, and uncoupling of respiration was induced more easily in aged mitochondria. Milder effects on these functional parameters were observed in SAMR1 mice. A similar dysfunction was also observed in heart mitochondria of SAMP8 mice at 12 months of age. The amount of Bcl-x in liver mitochondria was slightly decreased in SAMP8. We suggest that these changes in mitochondrial function may be related to the shorter life span of the senescence accelerated mouse.
自由基对线粒体中的DNA、蛋白质和脂质造成的氧化损伤可能是衰老的一个因素。对快速老化小鼠（SAMP8）和抗老化亚系（SAMR1）肝脏线粒体中的氧化磷酸化进行了评估。在衰老过程中，SAMP8肝脏线粒体的呼吸控制率下降，据估计，在18个月大时，这种呼吸控制值表明可能不足以提供正常细胞代谢所需的ATP合成。此外，作为ATP合成效率指标的ADP/O在18个月大时降低。随着衰老，SAMP8小鼠肝脏线粒体中依赖二硝基苯酚的解偶联呼吸显著下降，这表明衰老的SAMP8小鼠线粒体中的能量转移机制存在功能障碍。随着衰老，SAMP8小鼠肝脏线粒体中钙的主动摄取明显功能失调，并且在衰老的线粒体中更容易诱导呼吸解偶联。在SAMR1小鼠中观察到对这些功能参数的影响较小。在12个月大的SAMP8小鼠的心脏线粒体中也观察到类似的功能障碍。SAMP8肝脏线粒体中Bcl-x的量略有下降。我们认为线粒体功能的这些变化可能与快速老化小鼠较短的寿命有关。
