Conde-Pérezprina Juan C, Luna-López Armando, González-Puertos Viridiana Y, Zenteno-Savín Tania, León-Galván Miguel Angel, Königsberg Mina
Departamento de Ciencias de la Salud, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana Iztapalapa, México, DF, Mexico.
Age (Dordr). 2012 Dec;34(6):1473-92. doi: 10.1007/s11357-012-9399-5. Epub 2012 Mar 28.
The accumulation of oxidative damage to biomolecules, such as DNA, is known to induce alterations in the cell's mechanisms and structure that might lead to the aging process. DNA mismatch repair system (MMR) corrects base mismatches generated during DNA replication that have escaped the proofreading process. In addition, antioxidant enzymes can reduce reactive oxygen species effects in order to protect cells from oxidizing damage. In order to determine the importance of these associated factors during the aging process, in this study, levels of MMR proteins MSH2 and MLH1, as well as microsatellite markers, were compared in liver, lung, and brain of juvenile, adult, and old, both female and male, individuals from two species of wild bats: the short-lived Myotis velifer and the longer lived Desmodus rotundus. Catalase, glutathione peroxidase, and superoxide dismutase were also analyzed to determine if the antioxidant protection correlates negatively with DNA damage. Antioxidant activities were higher in the longer lived D. rotundus than in M. velifer. Furthermore, old M. velifer but not old D. rotundus bats had reduced MMR levels and increased microsatellite instability. Therefore, although our results correlate the reduced MMR efficiency, the deficient antioxidant activity, and the increase in DNA damage with the aging process, this is not always true for all living organisms.
已知生物分子(如DNA)的氧化损伤积累会诱导细胞机制和结构的改变,这可能导致衰老过程。DNA错配修复系统(MMR)可校正DNA复制过程中产生且未经过校对过程的碱基错配。此外,抗氧化酶可以降低活性氧的影响,以保护细胞免受氧化损伤。为了确定这些相关因素在衰老过程中的重要性,在本研究中,对两种野生蝙蝠(寿命较短的绒毛鼠耳蝠和寿命较长的吸血蝠)的幼年、成年和老年个体(包括雌性和雄性)的肝脏、肺和脑中的MMR蛋白MSH2和MLH1水平以及微卫星标记进行了比较。还分析了过氧化氢酶、谷胱甘肽过氧化物酶和超氧化物歧化酶,以确定抗氧化保护是否与DNA损伤呈负相关。寿命较长的吸血蝠的抗氧化活性高于绒毛鼠耳蝠。此外,老年绒毛鼠耳蝠而非老年吸血蝠的MMR水平降低,微卫星不稳定性增加。因此,尽管我们的结果将MMR效率降低、抗氧化活性不足和DNA损伤增加与衰老过程联系起来,但并非所有生物体都是如此。