THE INCREASE IN THE INDUCTION OF IL-2 EXPRESSION WITH CALORIC RESTRICTION IS CORRELATED TO CHANGES IN THE TRANSCRIPTION FACTOR NFAT

The objective of this study was to determine if the increase in the in duction of interleukin-2 (IL-2) expression with caloric restriction co rrelates with changes in binding activity of the IL-a-specific transcr iption factor NFAT (nuclear factor of activated T cells) and/or the ub iquitous transcription factor AP-1 in T cells from male Fischer 344 ra ts. Splenic T cells were isolated from young (6-month) and old (24-mon th) rats fed ad libitum and from old (24-month) rats fed a restricted diet (40% caloric restriction) that began at 6 weeks of age. T cells w ere stimulated with concanavalin A (Con A) and the expression of IL-2 and the DNA binding activity of the transcription factors NFAT and AP- 1 were measured in these cells. We found that the induction of IL-2 ac tivity and mRNA levels decreased with age and that caloric restriction significantly (P < 0.05) reduced the age-related decline in IL-2 expr ession. The ability of nuclear extracts from T cells isolated from old rats fed ad libitum and restricted old rats to bind to the NFAT oligo nucleotide or AP-1 oligonucleotide decreased with age. Caloric restric tion significantly (P < 0.05) reduced the age-related decline in NFAT but had no significant effect on AP-1 binding activity. We also measur ed the induction of c-fos and c-jun expression by Con A in T cells fro m young and old rats fed ad libitum or caloric-restricted diet. The in duction of c-fos protein and mRNA levels but not c-jun protein or mRNA levels decreased significantly with age. Caloric restriction signific antly (P < 0.05) reduced the age-related decline in c-fos expression b ut had no significant effect on c-jun expression. Therefore, the incre ase in IL-2 expression with caloric restriction correlates with an inc rease in binding activity of transcription factor NFAT and an increase in the expression of c-fos, which is a component of the NFAT-protein complex. (C) 1997 Academic Press.