The age-related decline in the induction of IL-2 transcription is correlated to changes in the transcription factor NFAT.

The effect of aging on the induction of IL-2 transcription by concanavalin A was studied in spleen lymphocytes isolated from young (4-6 months) and old (24 months) male Fischer 344 rats. The induction of IL-2 mRNA levels and IL-2 transcription were 40 to 50% lower for spleen lymphocytes isolated from old rats compared to spleen lymphocytes isolated from young rats. Because the transcription factor NFAT (nuclear factor activating IL-2 transcription) plays a major role in the regulation of IL-2 transcription, the DNA binding activity of NFAT in nuclear extracts of concanavalin A-stimulated lymphocytes was measured using a gel shift assay. The ability of nuclear extracts isolated from either total spleen lymphocytes or T cells to bind the NFAT oligonucleotide decreased 50 to 60% with age. Therefore, the age-related decrease in the expression of IL-2 appears to occur at the level of transcription and involves the transcription factor NFAT.