Petrosillo Giuseppe, Matera Mariagiuseppa, Moro Nicola, Ruggiero Francesca M, Paradies Giuseppe
Department of Biochemistry and Molecular Biology, CNR Institute of Biomembranes and Bioenergetics, University of Bari, Italy.
Free Radic Biol Med. 2009 Jan 1;46(1):88-94. doi: 10.1016/j.freeradbiomed.2008.09.031. Epub 2008 Oct 14.
Reactive oxygen species (ROS) are considered a key factor in the heart aging process. Mitochondrial respiration is an important site of ROS generation and a potential contributor to heart functional changes with aging. We have examined the effects of aging on various parameters related to mitochondrial bioenergetics in rat heart, such as complex I activity, oxygen consumption, membrane potential, ROS production, and cardiolipin content and oxidation. A loss in complex I activity, state 3 respiration, and membrane potential was found in mitochondria with aging. The capacity of mitochondria to produce H(2)O(2) was significantly increased in aged rats. The mitochondrial content of cardiolipin, a phospholipid required for optimal activity of complex I, significantly decreased as a function of aging, whereas there was a significant increase in the level of oxidized cardiolipin. The lower complex I activity in mitochondria from aged rats could be almost completely restored to the level of young heart by exogenously added cardiolipin, but not by other phospholipids nor by peroxidized cardiolipin. It is proposed that aging causes heart mitochondrial complex I deficiency, which can be attributed to ROS-induced cardiolipin peroxidation. These results may prove useful in elucidating the mechanism underlying mitochondrial dysfunction associated with heart aging.
活性氧（ROS）被认为是心脏衰老过程中的关键因素。线粒体呼吸是ROS产生的重要部位，也是导致心脏功能随衰老而变化的潜在因素。我们研究了衰老对大鼠心脏中与线粒体生物能量学相关的各种参数的影响，如复合体I活性、氧气消耗、膜电位、ROS产生以及心磷脂含量和氧化情况。研究发现，随着衰老，线粒体中的复合体I活性、状态3呼吸和膜电位均有所下降。老年大鼠线粒体产生H₂O₂的能力显著增加。心磷脂是复合体I发挥最佳活性所需的一种磷脂，其线粒体含量随衰老显著降低，而氧化心磷脂的水平则显著升高。通过外源添加心磷脂，老年大鼠线粒体中较低的复合体I活性几乎可以完全恢复到年轻心脏的水平，但其他磷脂或过氧化心磷脂则无法做到。研究表明，衰老会导致心脏线粒体复合体I缺乏，这可能归因于ROS诱导的心磷脂过氧化。这些结果可能有助于阐明与心脏衰老相关的线粒体功能障碍的潜在机制。
