Although weaning-initiated dietary restriction of rodents is known to increase maximum survivorship and inhibit spontaneous late-life disease and immunologic aging, restriction begun in adulthood has been much less thoroughly evaluated. In the present studies, male mice ofa long-lived F1 (4)(5)(6) and is the only strategy known to slow age-related increases in mortality rates in homeotherms (7). Restriction also inhibits or delays (or both) the occurrence of many late-life diseases (8)(9)(10)(11) and retards the development of immunosenescence (12)(13)(14)(15)(16) (23) and rats (24). With regard to immunologic effects, only mouse splenocyte mitogen-induced T-cell proliferative responses (which are known to decline with age) have been looked at. These were increased in 16-to 17-mo-old mice restricted from 12 mo of age (14) and in 22-mo-old mice restricted from 17 mo of age (25).The present studies, done with male mice of the long-lived (C3H.SW/Sn X C57BL10.RIII/Sn) F1 strain (C3B10RF,),were aimed at providing further information on the impact of gradually imposed adult-initiated diet restriction on immunologic aging and spontaneous cancer incidence.MATERIALS AND METHODS Mice. C3B1ORF1 mice bred in our animal facilities were studied. Those fed Purina lab chow ad lib have a mean lifespan of ""28 mo, and those restricted at weaning have a mean lifespan of "-40 mo. Lifespan was not determined in the present experiments as all mice were killed and studied for immune parameters and cancer incidence. Stimulator cells in the cell-mediated lymphocytotoxicity (CML) study came from DBA male mice (H-2d; Jackson Laboratories).Diet Strategies. Three hundred male mice weaned at 3 to 4 wk of age were housed in groups of 4-6 with free access to Purina lab chow. At 12 mo, mice were individually caged and randomly assigned to one of two diet categories. (i) Purina
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