All proteins are continually broken down and resynthesized in living cells. There are several different pathways for protein degradation, and we study one pathway by which cytosolic proteins can be taken up and degraded within lysosomes. Substrate proteins have a common peptide motif that targets them to this pathway of proteolysis called chaperone-mediated autophagy. Molecular chaperones in the cytosol and in the lysosome lumen stimulate the transport of substrate proteins, and a receptor for the substrates in the lysosomal membrane has been identified. Several important intracellular proteins are substrates of this pathway of proteolysis. We are currently examining how receptor levels are regulated in the lysosomal membrane and are also hunting for other molecular components of the protein import pathway.This pathway of proteolysis is markedly reduced in senescent fibroblasts and in livers from old rats. This reduced proteolysis may cause the eventual accumulation of aberrant proteins containing a variety of modifications.The pathway is reduced in senescent cells because of a reduced amount of receptor in the lysosomal membrane. We are trying to increase the expression of the receptor in senescent cells.