Effect of caloric restriction and aging on transcriptional regulation of IL-2 gene in rat lymphocytes

The objective of this study was to determine if caloric restriction would alter the agerelated decline in IL-2 expression by splenic T cells from male Fischer 344 rats. The induction of IL-2 activity and mRNA levels by concanavalin A (con A) were 60% and 65% lower in T cells isolated from old (24 months) rats compared to T cells isolated from young (6 months) rats. However, the expression of IL-2 was increased for T cells isolated from old (24 months) rats fed a restricted (40% restriction of caloric intake) compared to T cells isolated from age-matched control rats. Because the transcription factor NFAT (nuclear factor of activated IL-2 transcription) plays a major role in the regulation of IL-2 transcription, the DNA binding activity of NFAT in nuclear extracts con A-stimulated T cells was measured using gel shift assay. The ability of nuclear extracts isolated from splenic T cells to bind the NFAT oligonucleotide decreased 55% with age. However, the NFAT binding activity was increased for T cells isolated from old rats fed a restricted diet compared to T cells isolated from age-matched control rats- Because the T cell-specific transcription factor NFAT and the ubiquitous transcription factor AP-1 have been shown to contain Fos and Jun proteins, the induction of c-fos, c-jun, and AP-1 binding activity by conA-stimulated T cells were measured. The induction of c-fos and c-jun mRNA levels, and AP-1 binding activity by conA decreased with age and caloric restriction enhanced c-fos expression but did not significantly affect c-jun expression or AP-1 binding activity. Thus, the increase in NFAT bindine activity and c-fos exoression with caloric restriction is correlated to an increase in IL-2 expression.