THE EFFECT OF AGE ON FORMATION AND ELIMINATION OF AUTOPHAGIC VACUOLES IN MOUSE HEPATOCYTES

To gain an understanding of the mechanisms of lipofuscin (LF) accumulation in aging cells we studied both the formation and the elimination of autophagic vacuoles (AV) in hepatocytes of adult (5-6 months) and old (20-21 months) CBA male mice. For the evaluation of AV formation we determined the degree of AV accumulation 4 h after the injection of vinblastine, which blocks the fusion of AV with lysosomes. Other animals were treated with Triton X-100, which provokes the appearance of AV, and then, after 4 h, with cycloheximide to block the appearance of newly formed AV. AV elimination was then evaluated during the next 30 minutes. In our quantitative electron microscopic study of the liver tissue of these mice, we found a decrease in AV formation rate as well as a decrease in the intensity of AV elimination in hepatocytes of old versus young adult animals. The results indicate that the slowing down of AV elimination with age may play an important role in LF accumulation. Further, LF accumulation manifests itself despite decreased autophagy in aging.