Aging influences multiple indices of oxidative stress in the heart of the Fischer 344/NNia x Brown Norway/BiNia rat

We report the influence of aging on multiple markers of oxidative-nitrosative stress in the heart of adult ( 6-month), aged ( 30-month) and very aged (36-month) Fischer 344/ NNiaHSd x Brown Norway/ BiNia ( F344/ NXBN) rats. Compared to adult ( 6-month) hearts, indices of oxidative ( superoxide anion [ O-2(center dot-)], 4-hydroxy-2-nonenal [ 4-HNE]) and nitrosative (protein nitrotyrosylation) stress were 34.1 +/- 28.1%, 186 +/- 28.1% and 94 +/- 5.8% higher, respectively, in 36-month hearts and these findings were highly correlated with increases in left ventricular wall thickness ( r > 0.669; r > 0.710 and P < 0.01, respectively). Regression analysis showed that increases in cardiac oxidative-nitrosative stress with aging were significantly correlated with changes in the expression and/ or regulation of proteins involved in transcriptional ( NF-kappa B) activities, signaling ( mitogen-activated protein kinases along with Src), apoptotic ( Bcl-2, Traf-2), and cellular stress (HSPs). These results suggest that the aging F344/ NXBN heart may be highly suited for unraveling the molecular events that lead to age-associated alterations in cardiac oxidative stress.