Csiszar Anna, Labinskyy Nazar, Orosz Zsuzsanna, Xiangmin Zhao, Buffenstein Rochelle, Ungvari Zoltan
Department of Physiology, New York Medical College, Valhalla, NY 10595, USA.
Am J Physiol Heart Circ Physiol. 2007 Aug;293(2):H919-27. doi: 10.1152/ajpheart.01287.2006. Epub 2007 Apr 27.
The naked mole rat (NMR; Heterocephalus glaber) is the longest-living rodent known [maximum lifespan potential (MLSP): >28 yr] and is a unique model of successful aging showing attenuated declines in most physiological function. This study addresses age-related changes in endothelial function and production of reactive oxygen species in NMR arteries and vessels of shorter-living Fischer 344 rats (MLSP: approximately 3 yr). Rats exhibit a significant age-dependent decline in acetylcholine-induced responses in carotid arteries over a 2-yr age range. In contrast, over a 10-yr age range nitric oxide (NO)-mediated relaxation responses to acetylcholine and to the NO donor S-nitrosopencillamine (SNAP) were unaltered in NMRs. Cellular superoxide anion (O(2)(*-)) and H(2)O(2) production significantly increased with age in rat arteries, whereas they did not change substantially with age in NMR vessels. Indicators of apoptotic cell death (DNA fragmentation rate, caspase 3/7 activity) were significantly enhanced ( approximately 250-300%) in arteries of 2-yr-old rats. In contrast, vessels from 12-yr-old NMRs exhibited only a approximately 50% increase in apoptotic cell death. In the hearts of NMRs (2 to 26 yr old), expression of endothelial NO synthase, antioxidant enzymes (Cu,Zn-SOD, Mn-SOD, catalase, and glutathione peroxidase), the NAD(P)H oxidase subunit gp91(phox), and mitochondrial proteins (COX-IV, ATP synthase, and porin, an indicator of mitochondrial mass) did not change significantly with age. Thus long-living NMRs can maintain a youthful vascular function and cellular oxidant-antioxidant phenotype relatively longer and are better protected against aging-induced oxidative stress than shorter-living rats.
裸鼹鼠（NMR；Heterocephalus glaber）是已知最长寿的啮齿动物[最大寿命潜能（MLSP）：>28岁]，是成功衰老的独特模型，其大多数生理功能衰退减缓。本研究探讨了裸鼹鼠以及寿命较短的Fischer 344大鼠（MLSP：约3岁）的动脉和血管中内皮功能与活性氧生成的年龄相关变化。在2年的年龄范围内，大鼠颈动脉对乙酰胆碱诱导的反应呈现出显著的年龄依赖性下降。相比之下，在10年的年龄范围内，裸鼹鼠对乙酰胆碱和一氧化氮（NO）供体S-亚硝基青霉胺（SNAP）的NO介导的舒张反应未发生改变。大鼠动脉中细胞超氧阴离子（O(2)(*-)）和H(2)O(2)的生成随年龄显著增加，而裸鼹鼠血管中的这些物质随年龄变化不大。2岁大鼠动脉中凋亡细胞死亡指标（DNA片段化率、半胱天冬酶3/7活性）显著增强（约250 - 300%）。相比之下，12岁裸鼹鼠的血管凋亡细胞死亡仅增加约50%。在2至26岁裸鼹鼠的心脏中，内皮型一氧化氮合酶、抗氧化酶（铜锌超氧化物歧化酶、锰超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶）、NAD(P)H氧化酶亚基gp91(phox)以及线粒体蛋白（细胞色素c氧化酶IV、ATP合酶和孔蛋白，线粒体质量指标）的表达随年龄无显著变化。因此，长寿的裸鼹鼠能够相对更长时间地维持年轻的血管功能和细胞氧化-抗氧化表型，并且比寿命较短的大鼠更能抵御衰老诱导的氧化应激。
