ALTERATIONS IN THE CHAPERONE ACTIVITY OF HSP70 IN AGING ORGANISMS

The reduced capacity to respond to stress is one of the major characte ristics of senescent organisms. This decline is a major cause of morbi dity and eventually has lethal consequences. Heat-shock proteins (HSPs ) constitute a major defense system which allows recovery from adverse modes of stress such as elevated temperatures, alcohol, toxic heavy m etals (e.g., cadmium), some forms of oxidative and post-ischemic stres s and other forms of environmental insults. It is, therefore, importan t to investigate the functional capacity of HSPs as a function of orga nismal age at the molecular level. We chose to test the major stress-i nducible form, HSP70. This protein was purified to homogeneity from li vers of young (6 months) and old (27 months) rats. Its functional capa city was examined by the ability to protect the activity of creatine k inase (CPK) and aldolase A (Aid A) treated at 56 degrees C and 51 degr ees C, respectively. We first established that when HSP70 is present d uring the heat treatment it protected CPK by 80-90% and Aid A by 50-60 %. This protection was specific and was essentially dependent upon ATP and Mg2+. Most important, HSP70 from old rats gave only 50% protectio n of CPK as compared to the protein of young animals. The significance of the results in terms of cellular physiology in aging is discussed. Copyright (C) 1997 Elsevier Science Ireland Ltd.