Calorie restriction increases Fas/Fas-ligand expression and apoptosis in murine splenic lymphocytes

One-month-old male ICR mice were fed a nutritionally adequate, semipurified diet, either ad libitum (AL) or calorie restricted (CR) (40% less food) fo r 6 months and were killed to obtain spleens. Flow cytometric analysis reve aled increased proportions of both CD4(+) and CD8(+) T cells in CR-fed mice compared to AL-fed mice. The T cell subsets of CR-fed mice were also found to have higher levels of plasma membrane Fas receptor expression. Similarl y, Fas-ligand (Fas-L) expression was higher in anti-CD3-stimulated CD4(+) a nd CD8(+) T cells. CR-fed mice also had increased numbers of annexin V-posi tive CD4 and CD8+ T cells in stimulated splenic lymphocytes suggesting an i ncreased potential for apoptosis, Fas and Fas-L gene expression in splenic lymphocytes, which correlated closely with the observed increased rate of a poptosis, was significantly increased in CR-fed mice compared to AL-fed mic e. In conclusion, these results indicate that CR increases the expression o f Fas and Fas-L which may contribute to the known beneficial effects of CR such as prolongation of life span by activating chronic physiologically med iated apoptosis. (C) 1999 Federation of European Biochemical Societies.