Alterations in the chaperone activity of HSP70 in aging organisms

The reduced capacity to respond to stress is one of the major characteristics of senescent organisms. This decline is a major cause of morbidity 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 metals (e.g., cadmium), some forms of oxidative and post-ischemic stress and other forms of environmental insults. It is, therefore, important to investigate the functional capacity of HSPs as a function of organismal age at the molecular level. We chose to test the major stress-inducible form, HSP70. This protein was purified to homogeneity from livers of young (6 months) and old (27 months) rats. Its functional capacity was examined by the ability to protect the activity of creatine kinase (CPK) and aldolase A (Ald A) treated at 56 degrees C and 51 degrees C, respectively. We first established that when HSP70 is present during the heat treatment it protected CPK by 80-90% and Ald A by 50-60%. This protection was specific and was essentially dependent upon ATP and Mg(2+). Most important, HSP70 from old rats gave only 50% protection of CPK as compared to the protein of young animals. The significance of the results in terms of cellular physiology in aging is discussed.