Sanz Alberto, Bartke Andrzej, Barja Gustavo
Department of Animal Biology-II (Animal Physiology), Faculty of Biology, Complutense University, Madrid, 28040 Spain.
J Am Aging Assoc. 2002 Jul;25(3):119-22. doi: 10.1007/s11357-002-0010-3.
The single gene mutation of Ames dwarf mice increases their maximum longevity by around 40% but the mechanism(s) responsible for this effect remain to be identified. This animal model thus offers a unique possibility of testing the mitochondrial theory of aging. In this investigation, oxidative damage to mitochondrial DNA (mtDNA) was measured for the first time in dwarf and wild type mice of both sexes. In the brain, 8-oxo,7,8-dihydro-2'-deoxyguanosine (8-oxodG) in mtDNA was significantly lower in dwarfs than in their controls both in males (by 32%) and in females (by 36%). The heart of male dwarfs also showed significantly lower mtDNA 8-oxodG levels (30% decrease) than the heart of male wild type mice, whereas no differences were found in the heart of females. The results, taken together, indicate that the single gene mutation of Ames dwarfs lowers oxidative damage to mtDNA especially in the brain, an organ of utmost relevance for aging. Together with the previous evidence for relatively lower level of oxidative damage to mtDNA in both long-lived and caloric restricted animals, these findings suggest that lowering of oxidative damage to mtDNA is a common mechanism of life extension in these three different mammalian models.
艾姆斯侏儒小鼠的单基因突变使其最大寿命延长了约40%，但其产生这种效应的机制仍有待确定。因此，这种动物模型为检验衰老的线粒体理论提供了独特的可能性。在本研究中，首次对雌雄侏儒小鼠和野生型小鼠的线粒体DNA（mtDNA）氧化损伤进行了测量。在大脑中，侏儒小鼠mtDNA中的8-氧代-7,8-二氢-2'-脱氧鸟苷（8-氧代脱氧鸟苷，8-oxodG）在雄性（降低32%）和雌性（降低36%）中均显著低于其对照组。雄性侏儒小鼠心脏中的mtDNA 8-氧代脱氧鸟苷水平也显著低于雄性野生型小鼠心脏（降低30%），而雌性心脏中未发现差异。综合这些结果表明，艾姆斯侏儒小鼠的单基因突变降低了mtDNA的氧化损伤，尤其是在大脑中，大脑是与衰老密切相关的器官。结合先前关于长寿和热量限制动物中mtDNA氧化损伤水平相对较低的证据，这些发现表明降低mtDNA的氧化损伤是这三种不同哺乳动物模型中延长寿命的共同机制。
