Melatonin causes gene expression in aged animals to respond to inflammatory stimuli in a manner differing from that of young animals.

Groups of younger and aged mice were fed either minimal basal diet or the same diet containing 40 ppm melatonin. After 9.3 weeks half of each of these 4 groups of animals received either an intraperitoneal injection of lipopolysaccharide (LPS) or of saline. Three hours after this treatment, all animals were killed and mRNA from brains extracted. Quantitative PCR was performed on 13 selected mRNA species reflecting various aspects of the inflammatory pathway, the melatonin receptor, and a key glycolytic enzyme. An overall trend observed was that the effect of melatonin in modulating LPS-provoked immune responses differed markedly in old and young animals. Melatonin tended to enhance the reaction of younger animals to LPS but suppressed the inflammatory response of older mice. This difference with aging suggests that key immune processes are markedly altered by aging. It is likely that the ability of the immune system to mount a defense is impaired in older animals.