We wish to extent our original observation that there exists in eukaryotes a system which transfers arginine from arginyl tRNA to a pre-existing protein's NH2-terminal and resulting in modification of the protein. This system is called a protein modification system ((PMS). We have observed that cells transformed with a temperature sensitive Rous sarcoma virus mutant contained a significantly elevated level of PMS activity when grown at the temperature permissive for transformation than when grown at the non-permissive temperature. We have also observed that mitochondria, chromatin, and erythrocyte ghosts, as well as cellular membranes, contain proteins which can accept arginine at their NH2-terminal end from arginyl tRNA by the PMS. Based on these observations we shall examine a possible role of this PMS in cellular aging by comparing the PMS at various passages of tissue culture adapted human cells (WI-38 IMR-90 or MRC5) as well as in animal tissues of different ages. This includes 1) quantitative measurement of PMS, 2) comparison of the degree of modification of various cellular organelles such as chromatin, membrane, mitochondria, ribosomes, 3) comparison of the acceptor proteins, 4) comparison of acceptor activity of cellular membrane and ribosomes of cytoplasm with membrane and ribosomes of mitochondrial origin, 5) studies on transcriptional activity of chromatin with mammalian RNA polymerases before and after modification by PMS, and 6) effect of cellular transformation or infection of late passaged human cells by SV40 on PMS activity.