Increased expression of mature cathepsin B in aging rat liver

Senescence has been proposed as an important safeguard against neoplasia. O ne of the hallmarks of cellular senescence in vitro as well as human aging in vivo is a reduced intracellular protein catabolism. The pathways affecte d and the mechanisms responsible for the decrease in overall protein turnov er in aging cells are not well understood. Our aim was to determine whether or not expression of one of the major hepatic lysosomal cysteine peptidase s, cathepsin B, changes during aging of Sprague-Dawley rats. Cathepsin B ac tivity was assessed in whole rat liver homogenates, and was found to be inc reased fourfold (P less than or equal to0.001) in aged livers compared with younger counterparts. This was paralleled by an at least a twofold increas e in mature cathepsin B protein. Nonetheless, Northern blot analysis of tot al liver RNA revealed no change in steady-state levels of cathepsin B mRNAs . These findings seem to contradict the present dogma according to which ag ing tissues have a reduced intracellular capacity to catabolise proteins. W e propose that our earlier observation of the accumulation of T-kininogen, a potent but reversible cysteine peptidase inhibitor, in aging rat liver ma y provide a plausible explanation for this discrepancy.