Modification of age-related immune decline in mice dietarily restricted from or after midadulthood

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 of a long-lived F1 hybrid strain were gradually restricted dietarily beginning at 12 mo or older until their body weights stabilized at 60-70% of controls. Underfeeding decreased the number of nucleated cells per spleen but increased the percentage of T cells. For mice restricted at 12, 17, or 22 mo and tested at various ages thereafter, the [3H]thymidine uptake of spleen cells after phytohemagglutinin stimulation significantly exceeded values for age-matched unrestricted controls. Restriction did not, however, alter either splenocyte responses to concanavalin A or to B-cell mitogens or phytohemagglutinin responses of peripheral lymph node cells. In the splenic plaque-forming cell response to injected sheep erythrocytes, restricted and control mice differed more clearly in response kinetics than in peak levels. The splenic cell-mediated lymphocytotoxic response to alloantigens was comparable in old mice (27-29 mo) restricted since 12 mo of age with that of young (5- to 6-mo) controls and was greater than that of age-matched old controls. Spontaneous tumors were observed less frequently in 19- to 25-mo-old mice restricted at 12 mo of age than in mice restricted at 17 mo or in controls. Our results indicate that appropriate food restriction initiated in adulthood influences immunosenescence and spontaneous tumor incidence in a fashion not unlike its weaning-initiated counterpart.