López-Lluch G, Rios M, Lane M A, Navas P, de Cabo R
Laboratorio Andaluz de Biología, Universidad Pablo de Olavide, Carretera de Utrera km 1, 41013 Sevilla, Spain.
Age (Dordr). 2005 Jun;27(2):153-60. doi: 10.1007/s11357-005-2726-3. Epub 2005 Dec 10.
Caloric restriction (CR) is known as the only non-genetic method proven to slow the rate of aging and extend lifespan in animals. Free radicals production emerges from normal metabolic activity and generates the accumulation of oxidized macromolecules, one of the main characteristics of aging. Due to its central role in cell bioenergetics, a great interest has been paid to CR-induced modifications in mitochondria, where CR has been suggested to decrease reactive oxygen species production. The plasma membrane contains a trans-membrane redox system (PMRS) that provides electrons to recycle lipophilic antioxidants, such as α-tocopherol and coenzyme Q (CoQ), and to modulate cytosolic redox homeostasis. In the present study, we have investigated age differences in the PMRS in mouse liver and their modulation by CR. Aging induced a decrease in the ratio of CoQ10/CoQ9 and α-tocopherol in liver PM from AL-fed mice that was attenuated by CR. CoQ-dependent NAD(P)H dehydrogenases highly increased in CR old mice liver PMs. On the other hand, the CoQ-independent NADH-FCN reductase activity increased in AL-fed animals; whereas, in mice under CR this activity did not change during aging. Our results suggest that liver PMRS activity changes during aging and that CR modulates these changes. By this mechanism CR maintains a higher antioxidant capacity in liver PM of old animals by increasing the activity of CoQ-dependent reductases. Also, the putative role of PMRS in the modulation of redox homeostasis of cytosol is implicated.
热量限制（CR）是已知唯一被证实能减缓动物衰老速度并延长寿命的非基因方法。自由基产生于正常代谢活动，会导致氧化大分子的积累，这是衰老的主要特征之一。由于其在细胞生物能量学中的核心作用，人们对CR引起的线粒体变化产生了浓厚兴趣，有研究表明CR可减少线粒体中活性氧的产生。质膜包含一个跨膜氧化还原系统（PMRS），该系统能提供电子以循环利用亲脂性抗氧化剂，如α-生育酚和辅酶Q（CoQ），并调节胞质氧化还原稳态。在本研究中，我们调查了小鼠肝脏中PMRS的年龄差异及其受CR的调节情况。衰老导致正常饮食喂养小鼠肝脏质膜中CoQ10/CoQ9和α-生育酚的比例降低，而CR可减轻这种降低。依赖CoQ的NAD(P)H脱氢酶在CR老年小鼠肝脏质膜中显著增加。另一方面，不依赖CoQ的NADH-FCN还原酶活性在正常饮食喂养的动物中增加；而在CR小鼠中，该活性在衰老过程中没有变化。我们的结果表明，肝脏PMRS活性在衰老过程中发生变化，且CR可调节这些变化。通过这种机制，CR通过增加依赖CoQ的还原酶活性，在老年动物的肝脏质膜中维持较高的抗氧化能力。此外，还涉及PMRS在调节胞质氧化还原稳态中的假定作用。
