Influence of controlled dietary restriction on immunologic function and aging.

The underfeeding regimens tested in rodents for life span prolongation and/or immunologic effects result in a complex blend of protein and energy restriction while offering at least adequate amounts of all other essential nutrients. Underfeeding started at weaning and continued throughout life represents the only proved way of slowing the rate of aging in homeotherms. Mounting evidence indicates that underfeeding initiated later in life may also influence life span favorably. Old mice after lifelong restriction, or moderately aged mice (16.5 months) after 4.5 months of restriction, display "younger" immune systems than do age-matched, normally fed controls, as judged by response to mitogens, the mixed lymphocyte reaction, and other determinants. The immunologic effects of underfeeding, when measured quite early in life, are strain-dependent in the mouse. Diets designed to restrict the intake per week of energy (but not protein) produce the same effects on immune response capacity in very young mice as do energy restricted, protein unbalanced regimens. Underfeeding early in life drastically dampens thymic growth and alters the timing of involution. Early restriction also produces a profound lowering of body temperature in young (C57BL/10Sn x C3H/HeDiSn)F1 females. On the other hand, temperature lowering was not observed in males of this hybrid fed normally for the first year of life and restricted for 3 months prior to measurement. The mechanisms behind these various effects of controlled dietary restriction (i.e., undernutrition without malnutrition) are poorly understood at present.