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腾讯登录PLoS ONE：脆弱的DNA修复机制降低了老化进程
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随着个体不断老化，DNA损伤及突变不断增多。目前已经认为，导致这样的结果主要是由于基因毒性压力的不断增加以及DNA修复能力的不断降低。但是这两种诱因并不是彼此孤立的，比如DNA损伤能够通过突变干扰DNA修复能力，反过来增加了未被修复的受损DNA的数量。
<!--more-->细胞能否在一段时间维持一个较高的DNA修复能力，或者这种修复能力是随着年龄增加而持续下降？
为了阐明这些机制，近日来自丹麦哥本哈根大学的研究人员利用多细胞系统建立了一个简单的衰老数学模型。
对该模型的研究发现:在组织水平，DNA修复速率并不会随着年龄增加而持续下降，反而是有一个特异性的高的或是稳定的DNA修复能力的延长期，随之到来的是修复速率的迅速下降。而且，高DNA修复能力持续时间的增加会降低了老化进程。
虽然咋一看这样的结论是违反常理的，脆弱的修复机制使得受损细胞更快的移动，为健康细胞释放了更多的空间。为什么一个单链DNA修复蛋白(比如Wrn或者是Blm)的突变并不会被其它的修复蛋白所补偿反而导致了更严重的老化失调，Kristian Moss Bendtsen表示，该发现对阐明这个问题具有重要意义。相关论文发表在5月2日的PLoS ONE。
<br/><strong>文献链接</strong><br/>
<a href="http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0036018">http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0036018</a>
<div>
<br/><strong>Fragile DNA Repair Mechanism Reduces Ageing in Multicellular Model</strong><br/>
Kristian Moss Bendtsen*, Jeppe Juul, Ala Trusina.
DNA damages, as well as mutations, increase with age. It is believed that these result from increased genotoxic stress and decreased capacity for DNA repair. The two causes are not independent, DNA damage can, for example, through mutations, compromise the capacity for DNA repair, which in turn increases the amount of unrepaired DNA damage.Despite this vicious circle, we ask, can cells maintain a high DNA repair capacity for some time or is repair capacity bound to continuously decline with age? We here present a simple mathematical model for ageing in multicellular systems where cells subjected to DNA damage can undergo full repair, go apoptotic, or accumulate mutations thus reducing DNA repair capacity.Our model predicts that at the tissue level repair rate does not continuously decline with age, but instead has a characteristic extended period of high and non-declining DNA repair capacity, followed by a rapid decline. Furthermore, the time of high functionality increases, and consequently slows down the ageing process, if the DNA repair mechanism itself is vulnerable to DNA damages.Although counterintuitive at first glance, a fragile repair mechanism allows for a faster removal of compromised cells, thus freeing the space for healthy peers. This finding might be a first step toward understanding why a mutation in single DNA repair protein (e.g. Wrn or Blm) is not buffered by other repair proteins and therefore, leads to severe ageing disorders.
</div>
随着个体不断老化，DNA损伤及突变不断增多。目前已经认为，导致这样的结果主要是由于基因毒性压力的不断增加以及DNA修复能力的不断降低。但是这两种诱因并不是彼此孤立的，比如DNA损伤能够通过突变干扰DNA修复能力，反过来增加了未被修复的受损DNA的数量。
<!--more-->细胞能否在一段时间维持一个较高的DNA修复能力，或者这种修复能力是随着年龄增加而持续下降？
为了阐明这些机制，近日来自丹麦哥本哈根大学的研究人员利用多细胞系统建立了一个简单的衰老数学模型。
对该模型的研究发现:在组织水平，DNA修复速率并不会随着年龄增加而持续下降，反而是有一个特异性的高的或是稳定的DNA修复能力的延长期，随之到来的是修复速率的迅速下降。而且，高DNA修复能力持续时间的增加会降低了老化进程。
虽然咋一看这样的结论是违反常理的，脆弱的修复机制使得受损细胞更快的移动，为健康细胞释放了更多的空间。为什么一个单链DNA修复蛋白(比如Wrn或者是Blm)的突变并不会被其它的修复蛋白所补偿反而导致了更严重的老化失调，Kristian Moss Bendtsen表示，该发现对阐明这个问题具有重要意义。相关论文发表在5月2日的PLoS ONE。
<br/><strong>文献链接</strong><br/>
<a href="http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0036018">http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0036018</a>
<div>
<br/><strong>Fragile DNA Repair Mechanism Reduces Ageing in Multicellular Model</strong><br/>
Kristian Moss Bendtsen*, Jeppe Juul, Ala Trusina.
DNA damages, as well as mutations, increase with age. It is believed that these result from increased genotoxic stress and decreased capacity for DNA repair. The two causes are not independent, DNA damage can, for example, through mutations, compromise the capacity for DNA repair, which in turn increases the amount of unrepaired DNA damage.Despite this vicious circle, we ask, can cells maintain a high DNA repair capacity for some time or is repair capacity bound to continuously decline with age? We here present a simple mathematical model for ageing in multicellular systems where cells subjected to DNA damage can undergo full repair, go apoptotic, or accumulate mutations thus reducing DNA repair capacity.Our model predicts that at the tissue level repair rate does not continuously decline with age, but instead has a characteristic extended period of high and non-declining DNA repair capacity, followed by a rapid decline. Furthermore, the time of high functionality increases, and consequently slows down the ageing process, if the DNA repair mechanism itself is vulnerable to DNA damages.Although counterintuitive at first glance, a fragile repair mechanism allows for a faster removal of compromised cells, thus freeing the space for healthy peers. This finding might be a first step toward understanding why a mutation in single DNA repair protein (e.g. Wrn or Blm) is not buffered by other repair proteins and therefore, leads to severe ageing disorders.
</div>
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