Tissue-specific changes of DNA repair protein Ku and mtHSP70 in aging rats and their retardation by caloric restriction

To provide an improved understanding of the molecular basis of the aging process, it is necessary to measure biological age on a tissue-specific basis. The role of DNA damage has emerged as a significant mechanism for determination of life span, and DNA repair genes and stress-response genes are also implicated in the aging process. In the present study, we investigated the changes of DNA-PK activity, especially Ku activity, in the various tissues including kidney, lung, testis and liver during aging and its correlation with mtHSP70 expression. We showed that the modulation of Ku activity during the aging process was highly tissue-specific as shown with highly impaired Ku activity in testis and unaffected Ku activity in liver with age, and the level of Ku70 or Ku80 was differentially expressed in each aging tissue. We found also that age-associated alteration of Ku70/80 was prevented or not prevented by caloric restriction (CR) in a tissue-specific manner. Age-related decline in Ku70 during the aging process was associated with the increase of mtHSP70, which could play a role as a predictive marker for aging related to Ku regulation, and CR retarded aging-induced mtHSP70. (C) 2003 Elsevier Ireland Ltd. All rights reserved.