Age-related alterations in cardiac lysosomes

Abstract

The activities and distributions of several lysosomal enzymes (cathepsin D, β-acetylglucosaminidase, and acid phosphatase) were measured in left ventricular tissue from rats and rabbits of different ages. In both species, the hearts from older animals had significantly higher total activities of cathepsin D. Acid phosphatase activity was similar at all ages tested, and glucosaminidase activity was either unchanged or lower in the older hearts. The proportion of total cathepsin D activity that was nonsedimentable (i.e. not particle-bound) was much greater in older hearts; changes in the nonsedimentable-to-sedimentable distribution were less marked for the other enzymes. Immunohistochemical staining of rabbit cathepsin D with a specific antiserum to the enzyme revealed that age-related increases in cathepsin D occurred most prominently in myocytes rather than interstitial cells. Myocytic organelles that stained positively for the enzyme were larger and more numerous in older hearts, but there was no apparent shift in the general localization of cathepsin D including no significant staining outside lysosomelike particles. The results indicate that major lysosomal changes develop with age, and that the changes are heterogeneous with regard to different lysosomal enzymes. In studies of the effects of experimental interventions on lysosomal function, it is of critical importance always to use age-matched controls. The activities and distributions of several lysosomal enzymes (cathepsin D, β-acetylglucosaminidase, and acid phosphatase) were measured in left ventricular tissue from rats and rabbits of different ages. In both species, the hearts from older animals had significantly higher total activities of cathepsin D. Acid phosphatase activity was similar at all ages tested, and glucosaminidase activity was either unchanged or lower in the older hearts. The proportion of total cathepsin D activity that was nonsedimentable (i.e. not particle-bound) was much greater in older hearts; changes in the nonsedimentable-to-sedimentable distribution were less marked for the other enzymes. Immunohistochemical staining of rabbit cathepsin D with a specific antiserum to the enzyme revealed that age-related increases in cathepsin D occurred most prominently in myocytes rather than interstitial cells. Myocytic organelles that stained positively for the enzyme were larger and more numerous in older hearts, but there was no apparent shift in the general localization of cathepsin D including no significant staining outside lysosomelike particles. The results indicate that major lysosomal changes develop with age, and that the changes are heterogeneous with regard to different lysosomal enzymes. In studies of the effects of experimental interventions on lysosomal function, it is of critical importance always to use age-matched controls.