Mechanism of the age-related decline in lymphocyte proliferation: Role of IL-2 production and protein synthesis

Although an age-related decline in mitogen-induced proliferation in spleen lymphocytes has been reported by numerous investigators, the molecular mechanism responsible is unknown. In this study, we compared the mitogen-induced proliferation, IL-2 production, and protein synthesis in spleen lymphocytes isolated from 4, 12, 20 and 30 month-old male Fischer F344 rats. IL-2 production by Con A-stimulated lymphocytes, as determined by the ability of the culture supernatants to support the growth of cultured T cells, declined over 72% between 4 and 30 months of age. This decline in IL-2 production paralleled a similar decrease in proliferation. Early protein synthesis by Con A-stimulated spleen lymphocytes was determined by measuring the incorporation of [³H]-valine into acid insoluble material, and this dropped 74% between 4 and 30 months of age. There was a strong correlation between the age-related decline in the three parameters tested. Based on these results, we propose that the age-related decline in protein synthesis may be the molecular basis for the similar decrease in IL-2 production and mitogenesis.