Intervention in the aging immune system: Influence of dietary restriction, dehydroepiandrosterone, melatonin, and exercise.

The decline in immunologic function with age is associated with an increase in susceptibility to infections and the occurrence of autoimmune diseases and cancers. Hence, the restoration of immunologic function is expected to have a beneficial effect in reducing pathology and maintaining a healthy condition in advanced age. A number of therapeutic strategies have been employed to intervene in the aging immune system. This article reviews the effect of dietary restriction (DR), dehydroepiandrosterone (DHEA) treatment, melatonin (MLT) therapy, and exercise on modulating the immune responses and retarding/reducing immunosenescence. DR has been subject to intensive research and is known to be the most efficacious means of increasing longevity, reducing pathology and enhancing immune function. The circulatory levels of the androgenic hormone DHEA and the pineal hormone MLT decrease with increasing age, and this decrease has been correlated with the age-related decline in the immune system. Therefore, the observation that immunosenescence is associated with low levels of DHEA and MLT has provided a rationale for therapeutic intervention. DHEA treatment and MLT therapy both exhibit immunostimulatory actions and preliminary reports indicate that hormonal (DHEA or MLT) substitution therapy reverses immunosenescence in mice. Similarly, exercise in some studies has been shown to enhance the immune response. However, these findings have not been confirmed by other laboratories. Thus, at the present time, it is difficult to draw any definitive conclusions on the efficacy of DHEA, MLT, and exercise on reversing or restoring the aging immune system.