|
HACS   小总结: 线粒体DNA改变与衰老相关的分子事件：线粒体处理氧自由基的能力和能力随着年龄增长而下降，这将使线粒体DNA在衰老过程中更容易发生突变，比如缺失，而缺失地线粒体DNA甚至可以出线粒体膜转移到核中。   文章标题： Mitochondrial DNA alterations as ageing-associated molecular events 复制英文标题，然后下拉到本文底部发送到后台
|核心内容： 线粒体DNA（mtDNA）是一种裸露的双链环状染色体外遗传元件，持续地暴露于含有大量活性氧和自由基的基质中。 线粒体处理这些氧自由基的能力和能力随着年龄增长而下降，这将使线粒体DNA在衰老过程中更容易发生突变。 在过去3年中，在老年人各种组织的线粒体DNA中发现了10多种不同类型的缺失。 其中一些仅在特定组织中发现，而另一些则出现在多个器官或组织中。 在这些缺失中，4977 bp的缺失是最普遍和最丰富的。 骨骼肌是大多数与衰老相关的线粒体DNA缺失的靶组织，并且经常被发现携带多个缺失。 线粒体DNA中各种缺失的起始年龄因个体和缺失类型而大不相同。 4977 bp的缺失已被独立证明发生在人类第三个十年早期各种组织的线粒体DNA中。（也就是说人到三十岁过后线粒体DNA就开始出现4977 bp缺失了。） 然而，7436 bp的缺失仅在30多岁的受试者心脏线粒体DNA中检测到。 其他的只出现在40岁以上的老年人身上。 在这些与衰老相关的线粒体DNA缺失的发病年龄上没有发现明显的性别差异。 与衰老相关的各种缺失可分为两组。 大多数缺失属于第一组，其中缺失的5’-和3’-末端断点两侧是4-bp或更长的直接重复序列。 第二组中的缺失发生频率较低，在缺失位点两侧没有明显的重复序列。 这两组线粒体DNA的缺失可能通过不同的机制发生。 第一组最有可能是由D-环机制复制线粒体DNA时的内部重组或滑动错配引起的。 被删除的线粒体DNA和被删除的DNA片段可能进一步降解或从线粒体逃逸，并转移到细胞核中。 有许多实验在核DNA中发现插入线粒体DNA序列。 迁移的线粒体DNA片段可能会改变某些核基因的信息含量和表达水平，从而促进衰老过程或导致癌症。 在衰老的动物和植物中也观察到与衰老相关的线粒体DNA变化。 我认为，线粒体DNA缺失和其他有待发现的突变是通常与衰老过程有关的分子事件。 Mitochondrial DNA (mtDNA) is a naked double-stranded circular extrachromosomal genetic element continuously exposed to the matrix that contains great amounts of reactive oxygen species and free radicals. The age-dependent decline in the capability and capacity of mitochondria to dispose these oxy-radicals will render mtDNA more vulnerable to mutations during the ageing process. During the past 3 years, more than 10 different types of deletions have been identified in the mtDNA of various tissues of old humans. Some of them were found only in a certain tissue but some others appeared in more than one organ or tissue. The 4977-bp deletion is the most prevalent and abundant one among these deletions. Skeletal muscle is the target tissue of most ageing-associated mtDNA deletions and has often been found to carry multiple deletions. The onset age of the various deletions in mtDNA varies greatly with individual and type of the deletion. The 4977-bp deletion has been independently demonstrated to occur in the mtDNA of various tissues of the human in the early third decade of life. However, the 7436-bp deletion was only detected in the heart mtDNA of human subjects in their late thirties. The others appeared only in older humans over 40 years old. No apparent sex difference was found in the onset age of these ageing-associated mtDNA deletions. The various ageing-associated deletions could be classified into two groups. Most of the deletions belong to the first group, in which the 5'- and 3'-end breakpoints of the deletion are flanked by 4-bp or longer direct repeats. The deletion in the second group occurs less frequently and shows no distinct repeat sequences flanking the deletion sites. These two groups of mtDNA deletions may occur by different mechanisms. The first group is most probably caused by internal recombination or slippage mispairing during replication of mtDNA by the D-loop mechanism. The deleted mtDNA and the deleted DNA fragment may be further degraded or escape from the mitochondria and get translocated into the nucleus. The latter route has been substantiated by many observations of inserted mtDNA sequences in the nuclear DNA. Thus, the fragments of migrating mtDNA may change the information content and expression level of certain nuclear genes and thereby promote the ageing process or cause cancer. Similar ageing-associated alterations of mtDNA have also been observed in aged animals and plants. I suggest that mtDNA deletions and other mutations to be discovered are molecular events generally associated with the ageing process. 参考文献： https://pubmed.ncbi.nlm./1383757/
底部是系统推送的广告，与本文内容无关 |
|
|
