Vascular aging in the longest-living rodent, the naked mole rat

Vascular aging in the longest-living rodent, the naked mole rat. Am J Physiol Heart Circ Physiol 293: H919 - H927, 2007. First published April 27, 2007; doi: 10.1152/ ajpheart. 01287.2006. 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: similar to 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-nitro-sopencillamine ( SNAP) were unaltered in NMRs. Cellular superoxide anion (O2(center dot-)) 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 (similar to 250 - 300%) in arteries of 2-yr-old rats. In contrast, vessels from 12-yr-old NMRs exhibited only a similar to 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.