Department of Genetics, University of Wisconsin, Madison, WI 53706, USA.
Mech Ageing Dev. 2010 Jul-Aug;131(7-8):480-6. doi: 10.1016/j.mad.2010.04.006. Epub 2010 Apr 29.
Age-related hearing loss (AHL) is a universal feature of mammalian aging and is the most common sensory disorder in the elderly population. Experimental evidence suggests that mitochondrial dysfunction associated with reactive oxygen species (ROS) plays a central role in the aging process of cochlear cells. Although it is well established that mitochondria are the major source of ROS in the cell, specific molecular mechanisms of aging induced by ROS remain poorly characterized. Here we review the evidence that supports a central role for Bak-mediated mitochondrial apoptosis in AHL. We also propose that this mechanism may be of general relevance to age-related cell death in long-lived post-mitotic cells of multiple tissues, providing an opportunity for a targeted therapeutic intervention in human aging.
年龄相关性听力损失(AHL)是哺乳动物衰老的普遍特征,也是老年人群中最常见的感觉障碍。实验证据表明,与活性氧(ROS)相关的线粒体功能障碍在耳蜗细胞衰老过程中起核心作用。尽管线粒体是细胞中 ROS 的主要来源已得到充分证实,但 ROS 诱导衰老的具体分子机制仍知之甚少。在这里,我们回顾了支持 Bak 介导的线粒体细胞凋亡在 AHL 中起核心作用的证据。我们还提出,这种机制可能与多种组织中长寿有丝分裂后细胞的与年龄相关的细胞死亡具有普遍相关性,为人类衰老的靶向治疗干预提供了机会。