Effects of calorie restriction on thymocyte growth, death and maturation

We previously reported that calorie restriction (CR) significantly delays t he spontaneous development of thymic lymphomas and other neoplasms in p53-d eficient mice and their wild-type littermates. The purpose of the present s tudy was to further characterize the anti-lymphoma effects of CR by assessi ng thymocyte growth, death and maturation in response to acute (6 day) and chronic (28 day) CR regimens. Male C57BL/6J mice fed a CR diet (restricted to 60% of control nn libitum intake) for 6 days displayed a severe reductio n in thymic size and cellularity, as well as a decrease in splenic size and cellularity; these declines were sustained through 28 days of CR, Mice mai ntained on a CR diet for 28 days also displayed a significant depletion in the cell numbers of all four major thymocyte subsets defined by CD4 and CD8 expression. Analysis within the immature CD4(-)8(-) thymocyte subset furth er revealed an alteration in normal CD44 and CD25 subset distribution. in p articular, CR for 28 days resulted in a significant decrease in the percent age of the proliferative CD44(-)25(-) subset. In addition, a significant in crease in the percentage of the early, pro-T cell CD44(+)25(-) population w as detected, indicative of a CR-induced delay in thymocyte maturation. Take n together, these findings suggest that CR suppresses (through several puta tive mechanisms) lymphomagenesis by reducing the pool of immature thymocyte s that constitute the lymphoma-susceptible subpopulation.