Treuting Piper M, Linford Nancy J, Knoblaugh Sue E, Emond M J, Morton John F, Martin George M, Rabinovitch Peter S, Ladiges Warren C
Department of Comparative Medicine, University of Washington, Seattle, WA 98195-7190, USA.
J Gerontol A Biol Sci Med Sci. 2008 Aug;63(8):813-22. doi: 10.1093/gerona/63.8.813.
We describe the effects of mitochondrially targeted catalase (MCAT) expression on end-of-life pathology in mice using detailed semiquantitative histopathological evaluation. We previously reported that the median and maximum life spans of MCAT mice were extended relative to those of wild-type littermates. We now report that MCAT expression is associated with reduced malignant nonhematopoietic tumor burden, reduced cardiac lesions, and a trend toward reduced systemic inflammation, with no effect on hematopoietic neoplasia or glomerulonephropathy. Combined disease burden and comorbidity are also reduced, and MCAT expression is not associated with any detrimental clinical effects. The results suggest that oxidative damage is involved in aging of C57BL/6J mice via modulation of a subset of age-associated lesions. Antioxidant interventions targeting mitochondria may therefore be a viable strategy for prevention or postponement of some age-associated diseases. The variability of the MCAT effect across tissues, however, illustrates the importance of developing semiquantitative histopathology for assessment of comorbidity in life-span studies.
我们使用详细的半定量组织病理学评估方法，描述了线粒体靶向过氧化氢酶（MCAT）表达对小鼠终末病理的影响。我们之前报道过，与野生型同窝小鼠相比，MCAT小鼠的中位寿命和最大寿命有所延长。我们现在报告，MCAT表达与恶性非造血肿瘤负担减轻、心脏病变减少以及全身炎症减轻的趋势相关，对造血系统肿瘤或肾小球肾炎无影响。联合疾病负担和合并症也有所减少，且MCAT表达与任何有害的临床效应均无关联。结果表明，氧化损伤通过调节一部分与年龄相关的病变参与C57BL/6J小鼠的衰老过程。因此，针对线粒体的抗氧化干预可能是预防或延缓某些与年龄相关疾病的可行策略。然而，MCAT效应在不同组织中的变异性说明了在寿命研究中开发半定量组织病理学以评估合并症的重要性。
