A fundamental element of the """"""""theory of aging"""""""" implicates a critical role of free radicals, principally due to ROS of mitochondrial origin. Individual mitochondria, in isolated cardiac myocytes, loaded with membrane potential (delta PSI)- and ROS-sensitive fluorophores and excited with scanning laser light show an abrupt loss of delta PSI coinciding with a burst of mitochondrial ROS-production, which we termed """"""""ROS-induced ROS release"""""""". This loss of delta PSI is due to ROS-induction of the mitochondrial permeability transition (MPT). Hypothesizing that aging is accompanied by an increasing sensitivity to free radical stress, we compared the susceptibility to MPT-induction by ROS (characterized as the time necessary for ROS produced via photoexcitation to induce the MPT) in myocytes from young (2-4 month) and old (24 month) rats. Compared to young rats, MPT-induction times in the aged rats were reduced by 40%, whilst the magnitude of the ROS-burst was significantly increased. This enhanced sensitivity to ROS in the aged group was largely abolished by Coenzyme Q10 supplementation, an effect unlikely to be due to non-specific ROS-scavenging because the ROS-sensitivity of young cells was unaffected by this treatment. Thus, the age-related enhancement in ROS-sensitivity in cardiac myocytes from aged rats may be the result of specific loss of respiratory chain constituents.
| Zorov, Dmitry B; Juhaszova, Magdalena; Yaniv, Yael et al. (2009) Regulation and pharmacology of the mitochondrial permeability transition pore. Cardiovasc Res 83:213-25 |
| Ahmet, Ismayil; Spangler, Edward; Shukitt-Hale, Barbara et al. (2009) Blueberry-enriched diet protects rat heart from ischemic damage. PLoS One 4:e5954 |
| Moon, Chanil; Krawczyk, Melissa; Paik, Doojin et al. (2006) Erythropoietin, modified to not stimulate red blood cell production, retains its cardioprotective properties. J Pharmacol Exp Ther 316:999-1005 |
| Zorov, Dmitry B; Juhaszova, Magdalena; Sollott, Steven J (2006) Mitochondrial ROS-induced ROS release: an update and review. Biochim Biophys Acta 1757:509-17 |
| Juhaszova, Magdalena; Rabuel, Christophe; Zorov, Dmitry B et al. (2005) Protection in the aged heart: preventing the heart-break of old age? Cardiovasc Res 66:233-44 |
| Zorov, Dmitry B; Kobrinsky, Evgeny; Juhaszova, Magdalena et al. (2004) Examining intracellular organelle function using fluorescent probes: from animalcules to quantum dots. Circ Res 95:239-52 |
| Juhaszova, Magdalena; Zorov, Dmitry B; Kim, Suhn-Hee et al. (2004) Glycogen synthase kinase-3beta mediates convergence of protection signaling to inhibit the mitochondrial permeability transition pore. J Clin Invest 113:1535-49 |
| Lakatta, Edward G; Sollott, Steven J (2002) Perspectives on mammalian cardiovascular aging: humans to molecules. Comp Biochem Physiol A Mol Integr Physiol 132:699-721 |
| Lakatta, E G; Sollott, S J; Pepe, S (2001) The old heart: operating on the edge. Novartis Found Symp 235:172-96; discussion 196-201, 217 |
| Zorov, D B; Filburn, C R; Klotz, L O et al. (2000) Reactive oxygen species (ROS)-induced ROS release: a new phenomenon accompanying induction of the mitochondrial permeability transition in cardiac myocytes. J Exp Med 192:1001-14 |
