Oxidative stress and aging: catalase is a longevity determinant enzyme

Abstract

Schriner and colleagues have reported an important advance in our understanding of the mechanisms controlling lifespan in mammalian species. A transgenic mouse strain was constructed (MCAT) with a C57BL/6J background that has about a 50-fold increase in expression in cardiac mitochondria and skeletal muscle of catalase enzyme activity. The MCAT strain was found to have reduced severity of age-dependent arteriosclerosis and increased genomic stability, as indicated by a decrease in oxidative stress and mitochondrial deletions in heart and muscle tissues. Most exciting, however, is that both median and maximum lifespan were increased about 17-21% compared to wild-type controls. It was disappointing that the Gompertz plot of the MCAT strain ran parallel to the wild-type control, indicating a delay in the onset of aging rather than a decrease in aging rate. Nevertheless, these results support the notion of a role for mitochondrial oxidative stress as a determinant of both healthspan and lifespan. In addition, the relatively large increase in lifespan resulting from upregulation of a single gene suggests the possibility that similar upregulation of relatively few key longevity determinant genes may result in dramatic increases in lifespan.