Retinal Aging and Sirtuins
Retinal Aging and Sirtuins
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DOI：
10.1159/000316484
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发表时间：
2010-09
影响因子：
2.1
通讯作者：
Y. Ozawa;Shunsuke Kubota;Toshio Narimatsu;K. Yuki;Takashi Koto;M. Sasaki;K. Tsubota
中科院分区：
文献类型：
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作者：
Y. Ozawa;Shunsuke Kubota;Toshio Narimatsu;K. Yuki;Takashi Koto;M. Sasaki;K. Tsubota
衰老过程涉及微环境的累积变化，导致细胞衰老或凋亡，以及随后的组织或器官功能障碍。导致DNA不稳定的多种外在和内在事件与衰老有关。含有不稳定DNA的细胞在生物学上是脆弱的，如果DNA损伤太大，细胞无法修复，它就会衰老或通过凋亡死亡。因此，细胞修复其DNA的能力决定了衰老的进程，至少部分是这样。在这里，我们专注于sirtuins，哺乳动物同源的酵母寿命延长分子，Sir2。在哺乳动物的sirtuin家族蛋白中，与酵母Sir2最相似的是SIRT1，它参与多种途径，包括DNA双链断裂的修复。虽然SIRT1在哺乳动物寿命中的作用尚不清楚，但它在整个视网膜中表达，在那里它可以抑制衰老。事实上，视网膜变性的突变小鼠模型显示SIRT1蛋白的异常亚细胞定位和加速的视网膜细胞凋亡。需要进一步的研究来阐明衰老或病变视网膜中DNA损伤和修复的机制，包括sirtuins的作用，这将有助于我们理解视网膜衰老的机制。
The process of aging involves the accumulating changes in the microenvironment that lead to cell senescence or apoptosis, and subsequent tissue or organ dysfunction. Multiple extrinsic and intrinsic events that cause DNA instability are associated with aging. Cells containing unstable DNA are biologically vulnerable, and if the DNA damage is too great for the cell to repair, it becomes senescent or dies by apoptosis. Thus, the cell’s capacity to repair its DNA determines the progress of aging, at least in part. Here, we focus on the sirtuins, the mammalian homologs of the yeast life-span-extending molecule, Sir2. Among the sirtuin family proteins in mammals, the one most similar to yeast Sir2 is SIRT1, which is involved in multiple pathways, including the repair of DNA double-strand breaks. Although the role of SIRT1 in mammalian longevity is not clear, it is expressed throughout the retina, where it may suppress aging. In fact, a mutant mouse model of retinal degeneration shows an abnormal subcellular localization of SIRT1 protein and accelerated retinal cell apoptosis. Further analyses are required to elucidate the mechanism of DNA damage and repair, including the contributions of the sirtuins, in the aged or diseased retinas, which will help us understand the mechanisms of retinal aging.