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.
Gamble
D A
DA
Department of Medicine, Cornell University Medical College, New York, NY 10021.
Schwab
R
R
Weksler
M E
ME
Szabo
P
P
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