Role of neuroimmunomodulation in aging.

Aging is accompanied by an impairment of the physiological systems including the nervous, endocrine and immune systems, as well as of the nervous-immune communication. This impairment could explain the loss of homeostasis as well as the increased morbidity and mortality that appear with age. In the context of neuroimmunomodulation, it is now accepted that the age-related impairment of immune functions is the cause of the increased vulnerability to infection, cancer and autoimmune diseases of aged animals. Moreover, since the functional capacity of the immune cells has been proposed as a marker of health, our group, using mice with premature senescence, long-lived mice and human centenarians, has ascertained that several immune functions are good markers of biological age and predictors of longevity. Surprisingly, although there is presently considerable research on the changes of the immune system with age, denominated immunosenescence, the data supporting the role of this system in aging are very scarce. With aging, the immune cells show an increase in oxidant and inflammatory compounds and a decrease in antioxidant defenses, which is more evident in phagocytic cells. This chronic oxidative stress, which has among its intracellular mechanisms the activation of NF-kappaB in the leukocytes, affects all cells and especially those of the regulatory systems. Thus, we have proposed a key involvement of oxidative changes of the immune system in aging. Accordingly, the administration of antioxidants improves both the nervous and immune functions, decreasing their oxidative stress, and consequently there is a significant increase in longevity.