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A potential impact of DNA repair on ageing and lifespan in the ageing model organism Podospora anserina: decrease in mitochondrial DNA repair activity during ageing.
Mechanisms of Ageing and Development ( IF 5.3 ) Pub Date : 2009-06-03 , DOI: 10.1016/j.mad.2009.05.003
Mette Soerensen 1 , Ricardo Gredilla , Mathis Müller-Ohldach , Alexandra Werner , Vilhelm A Bohr , Heinz D Osiewacz , Tinna Stevnsner
Affiliation  

The free radical theory of ageing states that ROS play a key role in age-related decrease in mitochondrial function via the damage of mitochondrial DNA (mtDNA), proteins and lipids. In the sexually reproducing ascomycete Podospora anserina ageing is, as in other eukaryotes, associated with mtDNA instability and mitochondrial dysfunction. Part of the mtDNA instabilities may arise due to accumulation of ROS induced mtDNA lesions, which, as previously suggested for mammals, may be caused by an age-related decrease in base excision repair (BER). Alignments of known BER protein sequences with the P. anserina genome revealed high homology. We report for the first time the presence of BER activities in P. anserina mitochondrial extracts. DNA glycosylase activities decrease with age, suggesting that the increased mtDNA instability with age may be caused by decreased ability to repair mtDNA damage and hence contribute to ageing and lifespan control in this ageing model. Additionally, we find low DNA glycosylase activities in the long-lived mutants grisea and DeltaPaCox17::ble, which are characterized by low mitochondrial ROS generation. Overall, our data identify a potential role of mtDNA repair in controlling ageing and life span in P. anserina, a mechanism possibly regulated in response to ROS levels.

中文翻译:

DNA 修复对衰老模型生物 Podospora anserina 衰老和寿命的潜在影响:衰老过程中线粒体 DNA 修复活性降低。

衰老的自由基理论指出,ROS 通过线粒体 DNA (mtDNA)、蛋白质和脂质的损伤,在与年龄相关的线粒体功能下降中起关键作用。与其他真核生物一样,在有性繁殖子囊菌 Podospora anserina 中,衰老与 mtDNA 不稳定和线粒体功能障碍有关。部分 mtDNA 不稳定性可能是由于 ROS 诱导的 mtDNA 损伤的积累而引起的,正如之前对哺乳动物所提出的,这可能是由与年龄相关的碱基切除修复 (BER) 减少引起的。已知 BER 蛋白质序列与鹅卵磷脂基因组的比对显示高度同源性。我们首次报告了鹅口疮线粒体提取物中存在 BER 活性。DNA糖基化酶活性随着年龄的增长而降低,表明随着年龄的增长 mtDNA 不稳定性增加可能是由于修复 mtDNA 损伤的能力下降引起的,因此有助于该衰老模型中的衰老和寿命控制。此外,我们在长寿突变体 grisea 和 DeltaPaCox17::ble 中发现低 DNA 糖基化酶活性,其特征在于低线粒体 ROS 生成。总体而言,我们的数据确定了 mtDNA 修复在控制 P. anserina 衰老和寿命方面的潜在作用,这是一种可能响应 ROS 水平而调节的机制。
更新日期:2009-05-30
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