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HACS   小總結(jié): 線粒體DNA改變與衰老相關(guān)的分子事件：線粒體處理氧自由基的能力和能力隨著年齡增長而下降，這將使線粒體DNA在衰老過程中更容易發(fā)生突變，比如缺失，而缺失地線粒體DNA甚至可以出線粒體膜轉(zhuǎn)移到核中。   文章標(biāo)題： Mitochondrial DNA alterations as ageing-associated molecular events 復(fù)制英文標(biāo)題，然后下拉到本文底部發(fā)送到后臺(tái)
|核心內(nèi)容： 線粒體DNA（mtDNA）是一種裸露的雙鏈環(huán)狀染色體外遺傳元件，持續(xù)地暴露于含有大量活性氧和自由基的基質(zhì)中。 線粒體處理這些氧自由基的能力和能力隨著年齡增長而下降，這將使線粒體DNA在衰老過程中更容易發(fā)生突變。 在過去3年中，在老年人各種組織的線粒體DNA中發(fā)現(xiàn)了10多種不同類型的缺失。 其中一些僅在特定組織中發(fā)現(xiàn)，而另一些則出現(xiàn)在多個(gè)器官或組織中。 在這些缺失中，4977 bp的缺失是最普遍和最豐富的。 骨骼肌是大多數(shù)與衰老相關(guān)的線粒體DNA缺失的靶組織，并且經(jīng)常被發(fā)現(xiàn)攜帶多個(gè)缺失。 線粒體DNA中各種缺失的起始年齡因個(gè)體和缺失類型而大不相同。 4977 bp的缺失已被獨(dú)立證明發(fā)生在人類第三個(gè)十年早期各種組織的線粒體DNA中。（也就是說人到三十歲過后線粒體DNA就開始出現(xiàn)4977 bp缺失了。） 然而，7436 bp的缺失僅在30多歲的受試者心臟線粒體DNA中檢測到。 其他的只出現(xiàn)在40歲以上的老年人身上。 在這些與衰老相關(guān)的線粒體DNA缺失的發(fā)病年齡上沒有發(fā)現(xiàn)明顯的性別差異。 與衰老相關(guān)的各種缺失可分為兩組。 大多數(shù)缺失屬于第一組，其中缺失的5’-和3’-末端斷點(diǎn)兩側(cè)是4-bp或更長的直接重復(fù)序列。 第二組中的缺失發(fā)生頻率較低，在缺失位點(diǎn)兩側(cè)沒有明顯的重復(fù)序列。 這兩組線粒體DNA的缺失可能通過不同的機(jī)制發(fā)生。 第一組最有可能是由D-環(huán)機(jī)制復(fù)制線粒體DNA時(shí)的內(nèi)部重組或滑動(dòng)錯(cuò)配引起的。 被刪除的線粒體DNA和被刪除的DNA片段可能進(jìn)一步降解或從線粒體逃逸，并轉(zhuǎn)移到細(xì)胞核中。 有許多實(shí)驗(yàn)在核DNA中發(fā)現(xiàn)插入線粒體DNA序列。 遷移的線粒體DNA片段可能會(huì)改變某些核基因的信息含量和表達(dá)水平，從而促進(jìn)衰老過程或?qū)е掳┌Y。 在衰老的動(dòng)物和植物中也觀察到與衰老相關(guān)的線粒體DNA變化。 我認(rèn)為，線粒體DNA缺失和其他有待發(fā)現(xiàn)的突變是通常與衰老過程有關(guān)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. 參考文獻(xiàn)： https://pubmed.ncbi.nlm./1383757/
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