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1 Physiology, New York Medical College, Valhalla, New York, United States
2 Department of Physiology, New York Medical College, Valhalla, New York, United States
3 Biology, City College of New York, New York, New York, United States
4 Physiology, New York Medical College, Valhalla, United States
* To whom correspondence should be addressed. E-mail: zoltan_ungvari{at}nymc.edu.
The naked mole-rat (NMR; Heterocephalus glaber) is the longest-living rodent known (maximum lifespan potential [MLSP]: >28 years) and 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 F344 rats (MLSP: ~3 years). Rats exhibit a significant age-dependent decline in acetylcholine-induced responses in carotid arteries over a two year age-range. In contrast, over a 10 year age range NO-mediated relaxation responses to acetylcholine and to the NO donor SNAP were unaltered in NMRs. Cellular O2.- and H2O2 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 (~250-300%) in arteries of 2 year old rats. In contrast, vessels from 12 year old NMRs exhibited only a ~50 % increase in apoptotic cell death. In the hearts of NMRs (2 to 26 years old) expression of eNOS, antioxidant enzymes (Cu,Zn-SOD, Mn-SOD, catalase and glutathione peroxidase), the NAD(P)H oxidase subunit gp91phox 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.
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