Intracellular protein degradation rates decrease with age in many tissues and 
organs. In cultured cells, chaperone-mediated autophagy, which is responsible 
for the selective degradation of cytosolic proteins in lysosomes, decreases with 
age. In this work we use lysosomes isolated from rat liver to analyze 
age-related changes in the levels and activities of the main components of 
chaperone-mediated autophagy. Lysosomes from "old" (22-month-old) rats show 
lower rates of chaperone-mediated autophagy, and both substrate binding to the 
lysosomal membrane and transport into lysosomes decline with age. A progressive 
age-related decrease in the levels of the lysosome-associated membrane protein 
type 2a that acts as a receptor for chaperone-mediated autophagy was responsible 
for decreased substrate binding in lysosomes from old rats as well as from late 
passage human fibroblasts. The cytosolic levels and activity of the 73-kDa 
heat-shock cognate protein required for substrate targeting to lysosomes were 
unchanged with age. The levels of lysosome-associated hsc73 were increased only 
in the oldest rats. This increase may be an attempt to compensate for reduced 
activity of the pathway with age.