Department of Neuroscience, Erasmus MC, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
Mech Ageing Dev. 2012 Feb-Mar;133(2-3):59-67. doi: 10.1016/j.mad.2011.12.003. Epub 2012 Jan 12.
Age-related loss of hearing and vision are two very common disabling conditions, but the underlying mechanisms are still poorly understood. Damage by reactive oxygen species and other reactive cellular metabolites, which in turn may damage macromolecules such as DNA, has been implicated in both processes. To investigate whether DNA damage can contribute to age-related hearing and vision loss, we investigated hearing and vision in Ercc1(δ/-) mutant mice, which are deficient in DNA repair of helix-distorting DNA lesions and interstrand DNA crosslinks. Ercc1(δ/-) mice showed a progressive, accelerated increase of hearing level thresholds over time, most likely arising from deteriorating cochlear function. Ercc1(δ/-) mutants also displayed a progressive decrease in contrast sensitivity followed by thinning of the outer nuclear layer of the eyeball. The strong parallels with normal ageing suggest that unrepaired DNA damage can induce age-related decline of the auditory and visual system.
年龄相关性听力和视力下降是两种非常常见的致残情况，但潜在机制仍不清楚。活性氧和其他活性细胞代谢物的损伤，进而可能损伤如 DNA 等大分子，这与这两个过程都有关。为了研究 DNA 损伤是否会导致与年龄相关的听力和视力下降，我们研究了 Ercc1(δ/-) 突变小鼠的听力和视力，该小鼠缺乏对扭曲 DNA 损伤和链间 DNA 交联的 DNA 修复。Ercc1(δ/-) 小鼠的听力水平阈值随时间呈进行性、加速性增加，很可能是由于耳蜗功能恶化所致。Ercc1(δ/-) 突变体还表现出对比度敏感性逐渐下降，随后眼球外核层变薄。这些与正常衰老的强烈相似性表明，未修复的 DNA 损伤可诱导听觉和视觉系统的与年龄相关的衰退。
