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

Abstract

One-month-old male ICR mice were fed a nutritionally adequate, semipurified diet, either ad libitum (AL) or calorie restricted (CR) (40% less food) for 6 months and were killed to obtain spleens. Flow cytometric analysis revealed 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. Similarly, Fas-ligand (Fas-L) expression was higher in anti-CD3-stimulated CD4+ and CD8+ T cells. CR-fed mice also had increased numbers of annexin V-positive CD4+ and CD8+ T cells in stimulated splenic lymphocytes suggesting an increased potential for apoptosis. Fas and Fas-L gene expression in splenic lymphocytes, which correlated closely with the observed increased rate of apoptosis, was significantly increased in CR-fed mice compared to AL-fed mice. In conclusion, these results indicate that CR increases the expression of Fas and Fas-L which may contribute to the known beneficial effects of CR such as prolongation of life span by activating chronic physiologically mediated apoptosis.

Caloric restriction favorably impacts metabolic and immune/inflammatory profiles in obese mice but curcumin/piperine consumption adds no further benefit

“…Previous studies have reported that CR administered to lean or obese rodents increases total T cell population and both CD4 + and CD8 + subpopulations [10,32,33]. Consistent with these previous results, in the current study, which focused on CD4 + T cells and their subpopulations, we found that spleens from CR mice had higher percentages of CD4 + T cells.…”

Inhibition of H2O2‐induced apoptosis of lymphocytes by calorie restriction during aging

“…Similar to ours and several other previous reports (Gartner et al, 1992;Luan et al, 1995;Reddy et al, 1999), the present study also showed that CR maintained a significantly higher proportion of CD4 ϩ cells compared to AL feeding. With age, CD8 ϩ cells were increased in AL-fed mice, but CR prevented the ageassociated increase of CD8 ϩ cells.…”

“…Further, we also observed strain variation in apoptosis in CR-fed mice. We have previously reported increased apoptosis in CR-fed MRL/lpr and a randomly bred ICR strain of mice with or without differences in Fas and Fas-mediated apoptosis (Luan et al, 1995;Reddy et al, 1999). However, our recent studies show differences in apoptosis between C57BL/6J and Balb/C mice maintained on an AL-or CR-fed diet.…”

“…In the case of autoimmune-prone mice, CR is found to delay the early loss of T-cell immune function and to decrease the formation of immune complexes in the kidneys (Chandrasekar et al, 1995b;Fernandes et al, 1995). CR has also been found to maintain naive T cells and prevent the rise of memory T cells with age in both short-and long-lived strains of mice and rats (Fernandes et al, 1994(Fernandes et al, , 1997Reddy et al, 1999). Earlier we reported that CR decreased the expression of mRNA coding for pro-inflammatory cytokines and increased the expression of mRNA coding for anti-inflammatory cytokines, including transforming growth factor beta (TGF␤), in B/W mice (Chandrasekar et al, 1995b).…”

Identification of the Apoptosis Activation Cascade Induced in Mammary Carcinomas by Energy Restriction

“…Moreover, the reports of apoptosis induction by ER in various cancer models are in marked contrast to reports in experimental models of aging that ER inhibits apoptosis (25)(26)(27). This situation underscores the importance of identifying the mechanisms that account for changes in rates of apoptosis induced by ER under both physiological and patho-physiological conditions.…”