Changes in cathepsin B and lipofuscin during development and aging in rat brain and heart.

While results with inhibitors of thiol proteases have led to the suggestion that the progressive increase with age of lipofuscin in post-mitotic and some stable cells may be due to an age-related decline in the activity of these enzymes (Ivy et al., 1989), no direct evidence has been yet presented to support this hypothesis. In this study Wistar female rats were killed at age of 5, 14, and 24 months and the amounts of lipofuscin were histologically quantitated in neurons of the left cerebral parietal cortex and in cardiac myocytes of left ventricle. The sites of cathepsin B activity histochemically detected were quantitated in sections from left cerebral parietal cortex and left ventricle, and the activity of this enzyme was also measured biochemically in brain and heart homogenates. In line with previous findings, the amounts of lipofuscin in neurons and cardiac myocytes increased linearly during development and aging (from 5 to 14 and from 14 to 24 mo.). The sites of cathepsin B activity histochemically detected in sections from cerebral cortex significantly increased from 5 to 14 mo., but remained unchanged from 14 to 24 mo, while in sections from the left cardiac ventricle these sites of activity remained unchanged during development, and significantly increased during aging. On the other hand the biochemically determined activities of cathepsin B in brain and heart homogenates remained unchanged from 5 to 14 mo., but significantly decreased from 14 to 24 mo. These results suggest that the increase in lipofuscin with age may not be due to an age-wise decline in cathepsin B activity.