Age-related changes in cellular localization and enzymatic activities of cathepsins B, L and D in the rat trigeminal ganglion neuron.

Altered localization and cellular level of three distinct lysosomal proteinases, cathepsins B (CB), L (CL), and D (CD), with aging were investigated in the rat trigeminal ganglion (TG) by immunohistochemical and quantitative analyses. At the light microscopic level, the intracytoplasmic distribution of these three enzymes was found to change with aging: These lysosomal proteinases in the TG of young rats (2-3 months of age) were widely and evenly distributed throughout the cytoplasm as coarse intracytoplasmic granules, whereas they were localized at focal cytoplasmic sites of the TG neurons of aged rats (28-31 months of age) as coarse aggregates. A similar distribution was observed with a major lysosomal membrane sialoglycoprotein having an apparent molecular mass of 107 kDa (LGP107). The cellular distribution of the three cathepsins as well as LGP107 in the TG neurons of aged rats corresponded well with that of autofluorescent lipofuscin. At the electron microscopic level, the age-related redistribution of these cathepsins in the TG neurons was found to be due to their great accumulation in autolysosomes localized at the focal perinuclear sites. The cellular levels of CB and CL determined by activity measurement in the TG of the young rats were 1.8 and 1.7 times as much as those of the aged rats respectively. In contrast, no significant difference was observed between the CD activities in the two age groups. These results strongly suggest that age related changes in localization and cellular level of CB, CL, and CD in TG neurons are closely linked with the increased formation of autolysosomes and lipofuscins, which is the most ubiquitous age-related cytological alteration.