Decreased steady state c-myc mRNA in activated T cell cultures from old humans is caused by a smaller proportion of T cells that transcribe the c-myc gene.
The proliferative response of T cells is known to decrease with age of the T cell donor. We now report that this proliferative defect affects both major subsets (CD4+, CD8- and CD4-, CD8+) of peripheral T cells from old humans. Furthermore, this proliferative defect can be detected within the first hours after addition of mitogen by a reduction in the steady state levels of c-myc mRNA in T cell cultures from old donors. Lymphocytes from old humans cultured with PHA have less than 50% of the level of c-myc message than do such cultures from young donors. Nuclear run-on assays suggest that the decreased steady state level of c-myc mRNA in cultures from old donors is caused by reduced transcription of the c-myc gene in T cells from old donors. The age-associated defect in transcription of the c-myc gene affects the second exon to a greater extent than the first, noncoding exon. Individual T lymphocytes from old donors that do express c-myc message, detected by in situ hybridization, have the same intracellular level of c-myc message as T lymphocytes from young donors. These data add additional support for the hypothesis that the proliferative defect of T lymphocytes from old humans is caused by the smaller fraction of T cells from old as compared with young humans that can be activated by mitogens to enter the G1 phase of the cell cycle.
Department of Medicine, Cornell University Medical College, New York, NY 10021.
D A
DA
Gamble
R
R
Schwab
M E
ME
Weksler
P
P
Szabo
D000375:Aging; D002478:Cells, Cultured; D015870:Gene Expression; D005796:Genes; D006801:Humans; D008213:Lymphocyte Activation; D009693:Nucleic Acid Hybridization; D010835:Phytohemagglutinins / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger / Q000235:genetics; D015183:Restriction Mapping; D013601:T-Lymphocytes / Q000502:physiology*; D014158:Transcription, Genetic
D010835:Phytohemagglutinins; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger