Melatonin and tumeric ameliorate aging-induced changes: implication of immunoglobulins, cytokines, DJ-1/NRF2 and apoptosis regulation.

Aging is associated with several biological, physiological, cellular and histological changes. In the present study, we investigated the effect of aging on different signaling pathways, including antioxidant system, apoptosis and immune status. Several natural products were used to ameliorate and block aging-related changes. Melatonin and turmeric have been known to ameliorate and decrease aging-related changes. However, the exact mechanism(s) of their action is not fully understood. In the present study, we tried to uncover the regulatory mechanism(s) by which melatonin and turmeric work against aging. We found that aging differentially regulated blood serum immunoglobulins; increased IgA and decreased IgE. Furthermore, all the serum cytokines investigated (TNF-α, IFN-γ, IL-6 and IL-8) were highly increased by aging. In addition, the antioxidant upstream regulators; DJ-1 and NRF2 were markedly repressed with aging in thymus tissues. We also found that aging induced apoptosis promoting genes p53 and Bax mRNA in thymus tissues. Finally, we found clear histological changes in thymus and spleen tissues. Administration of either melatonin or tumeric clearly ameliorated and blocked to some extinct the effect of aging. Altogether, aging was associated with downregulation of antioxidant regulators; DJ-1 and NRF2, promoted apoptosis and induced changes in the immune status. Furthermore, melatonin and tumeric markedly reversed the action of aging through activating DJ-1/NRF2 signaling pathway and inhibiting p53/Bax apoptotic pathway.