ANDZIAK, B.A.; BUFFENSTEIN, R.; O’CONNOR, T.P.; The City College of New York, CUNY & The Graduate School and University Center, CUNY; The City College of New York, CUNY & The Graduate School and University Center, CUNY; The City College of New York, CUNY & The Graduate School and University Center, CUNY: Oxidative damage tolerance in naked mole-rats; a possible explanation for pronounced longevity.

Differences in lifetime oxidative damage accrual may account for variation in maximum lifespan (MLSP) among species. Oxidative damage levels reflect a net difference between Reactive Oxygen Species (ROS) generation and their removal by antioxidants. Naked mole-rats (Heterocephalus glaber) are the longest-lived rodent species known (MLSP ca. 28y), exceeding allometric predictions for MLSP by ca. 8 times. We hypothesized that their extreme longevity, compared to much shorter-lived, yet similarly-sized mice (Mus musculus, MLSP 4y), may be due to reduced levels of oxidative damage accrual and/or superior antioxidant activity. We examined if 1) oxidative damage levels vary between these two species, and 2) mole-rats have greater antioxidant activity than mice. Net oxidative damage (lipid peroxidation levels) and antioxidant activity, namely mitochondrial and cytosolic/nuclear superoxide dismutase (SOD) were assessed in liver of young, middle-aged and old individuals of both species using colorimetric assays (Oxis Research). Oxidative damage in the oldest mole-rat group (120 mo) was markedly higher than in the oldest mouse cohort (24 mo). Even young mole-rats (25 mo) had damage levels greater than oldest mice. Liver SOD activities were also higher in naked mole-rats. These results suggest that the 7-fold greater MLSP of mole-rats than mice is not only due to superior antioxidant activities, but may also result from greater tolerance to oxidative damage. Support provided by a SICB GIAR grant to BA.