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 concanav alin A was studied in spleen lymphocytes isolated from young (4-6 mont hs) and old (24 months) male Fischer 344 rats. The induction of IL-2 m RNA levels and IL-2 transcription were 40 to 50% lower for spleen lymp hocytes isolated from old rats compared to spleen lymphocytes isolated from young rats. Because the transcription factor NFAT (nuclear facto r activating IL-2 transcription) plays a major role in the regulation of IL-2 transcription, the DNA binding activity of NFAT in nuclear ext racts of concanavalin A-stimulated lymphocytes was measured using a ge l shift assay. The ability of nuclear extracts isolated from either to tal spleen lymphocytes or T cells to bind the NFAT oligonucleotide dec reased 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. (C) 1995 Academic Press, Inc.