Many changes in the levels of various enzymes have been found as a function of age. Typically, these changes are small, on the order of three-fold or less. It would be of value to have genes that change much more dramatically with age--perhaps several orders of magnitude--as markers for the aging process. It would be especially useful to have different markers of this type for different tissues; this would allow us to follow segmental aging changes. Finally, if such genes are directly controlled by some cellular program for aging, their isolation may allow us to get a closer look at this program. Our approach to this analysis is to make cDNA libraries from young (3 month) and old (26 month) mice from the GRC colony. These libraries will be compared by hybridization techniques to see what RNA messages are present in high copy in one library but not in another. The structure and tissue-specific expression of these messages will then be examined.