衰老的黑腹果蝇线粒体RNA水平降低而线粒体DNA缺失不积累

Steven R Schwarze , Richard Weindruch , Judd M Aiken
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引用次数: 26

摘要

据报道,随着年龄的增长,黑腹果蝇和许多其他动物的电子传递系统(ETS)活动也会下降。有人提出,这些变化在老化过程中起重要作用。ETS下降归因于线粒体核酸损伤。我们分析了不同年龄的黑腹龙(胚胎到60天大的成年)线粒体DNA (mtDNA)基因组突变的存在。虽然鉴定出具有较大DNA缺失(高达5 kb)的mtDNA基因组,但丰度很低,并且在整个成年期保持不变。因此,这些mtDNA缺失似乎并不足以引起ETS活动的大幅下降。接下来,我们分析了不同年龄的D. melanogaster的四种线粒体编码和两种核编码的ETS转录本的丰度。随着年龄的增长,线粒体转录本的丰度下降了5- 10倍,核编码转录本的丰度下降了2 - 5倍。根据飞行损失对果蝇进行分离,以区分生理年龄和实足年龄。研究发现,在30天龄时能够飞行的昆虫,其cox 1线粒体编码RNA的丰度是不会飞行的昆虫的4倍。然而,在核编码的β- atp酶RNA水平上没有明显差异,这表明只有线粒体RNA (mtRNA)的下降与预期寿命有关。
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Decreased mitochondrial RNA levels without accumulation of mitochondrial DNA deletions in aging Drosophila melanogaster

Declines in electron transport system (ETS) activity have been reported to occur with advancing age in Drosophila melanogaster and many other animals. It has been proposed that these changes are importantly involved in the aging process. ETS decline has been attributed to mitochondrial nucleic acid damage. We analyzed various ages of D. melanogaster (embryos to 60-day-old adults) for the presence of mutated mitochondrial DNA (mtDNA) genomes. Although mtDNA genomes with large DNA deletions (up to 5 kb) were identified, abundance was low and remained constant throughout adult life. Therefore, these mtDNA deletions do not appear to be sufficiently abundant to cause large declines in ETS activity. Next, we analyzed various ages of D. melanogaster for the abundance of four mitochondrial-encoded and two nuclear-encoded ETS transcripts. The abundance of the mitochondrial transcripts declined 5–10-fold, while the nuclear-encoded transcripts declined 2–5-fold with advancing age. Separation of flies on the basis of flight loss was used to distinguish physiologic age from chronological age. Insects capable of flight at 30 days of age were found to have a 4-fold higher abundance of cox I mitochondrial-encoded RNA compared to flightless insects. No difference, however, was apparent in the nuclear-encoded β-ATPase RNA level, suggesting only mitochondrial RNA (mtRNA) declines are associated with life expectancy.

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