Differences in Liver TFAM Binding to mtDNA and mtDNA Damage between Aged and Extremely Aged Rats
Differences in Liver TFAM Binding to mtDNA and mtDNA Damage between Aged and Extremely Aged Rats
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DOI：
10.3390/ijms20102601
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发表时间：
2019-05-02
影响因子：
5.6
通讯作者：
Pesce, Vito
中科院分区：
文献类型：
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作者：
Chimienti, Guglielmina;Picca, Anna;Pesce, Vito
虽然线粒体功能障碍被认为是衰老的主要特征，但对线粒体在延长寿命中的作用知之甚少。分析了老年（28月龄）和极老年（32月龄）大鼠肝脏的柠檬酸合酶活性、线粒体转录因子A（TFAM）含量、线粒体DNA（mtDNA）和4.8 Kb常见缺失内容。各年龄组之间的测定参数无显著差异。TFAM与mtDNA的结合和特定mtDNA区域中8-氧代脱氧鸟苷的发生率，包括mtDNA复制的起点（D环和Ori-L）和4.8 Kb缺失的16 bp长的直接重复序列1（DR 1）。与老年大鼠相比，在极老年大鼠的所有区域，TFAM结合率均降低。与28月龄组相比，在32月龄大鼠中检测到所有测定区域的氧化嘌呤发生率降低。8-oxo-deoxoguanosine和TFAM结合的mtDNA的发生率之间的显着正相关性被发现在D-Loop和Ori-L区域仅在28个月大的大鼠。在32个月大的大鼠中没有这种相关性表明在两个年龄组中TFAM结合的不同的微调调节，并支持衰老和延长衰老中存在两种不同的步伐。
While mitochondrial dysfunction is acknowledged as a major feature of aging, much less is known about the role of mitochondria in extended longevity. Livers from aged (28-month-old) and extremely aged (32-month-old) rats were analyzed for citrate synthase activity, mitochondrial transcription factor A (TFAM) amount, mitochondrial DNA (mtDNA), and 4.8 Kb common deletion contents. None of the assayed parameters differed significantly between age groups. TFAM-binding to mtDNA and the incidence of 8-oxo-deoxyguanosine in specific mtDNA regions, encompassing the origins of mtDNA replication (D-loop and Ori-L) and the 16-bp long direct repeat 1 (DR1) of the 4.8 Kb deletion, were determined. A decrease in TFAM binding was unveiled at all regions in extremely aged in comparison with aged rats. Reduced incidence of oxidized purines at all assayed regions was detected in 32-month-old rats compared with the 28-month-old group. A significant positive correlation between the incidence of 8-oxo-deoxoguanosine and TFAM-bound mtDNA was found at D-Loop and Ori-L regions only in 28-month-old rats. The absence of such correlation in 32-month-old rats indicates a different, fine-tuned regulation of TFAM binding in the two age groups and supports the existence of two different paces in aging and extended aging.