Protein degradation in the aging organism.

It is now generally accepted that protein degradation declines with age but a mechanism of action for this decline has not yet been delineated. Although intracellular and extracellular proteins can enter multiple pathways of degradation, there primarily appears to be two final mediators of this degradation, the lysosome and the proteasome. Studies on the effects of age on lysosomal function suggest that, if anything, lysosomal enzyme activity increases with age (Ward 2000). The peptidase activities of the proteasome are altered with age, but not in a consistent manner. There is a significant age-related decline of the PGPH activity, but the rate-limiting peptidase activity, ChT-L activity, as well as T-L activity have both been reported either to increase, not change, or decrease (Table 1). In addition, proteasomal degradation of casein does not appear to be altered with age. As a result, it has not been possible to definitively implicate either of the two primary final mediators of protein degradation, the lysosome and the proteasome, as mechanisms of action for the decline in protein degradation observed in the aging organism. However, there are experimental observations suggesting that age may have strong effects on both macroautophagic and the chaperone-mediated autophagic processes. Therefore, it is important that more research activity be devoted to the investigation of the effects of age on these processes as this may be where mechanism(s) of action for the age-related decline in protein degradation lies.