Role of Neuroimmunomodulation in Aging

Abstract

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-ĸB 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.

It takes nerves to fight infections: insights on neuro-immune interactions fromC. elegans

“…Increased age is also associated with a gradual impairment of the nervous system. Alterations in the nervous and immune systems with advanced age consequently perturb neuro-immune interactions in the elderly (De la Fuente, 2008). Studies of C. elegans have contributed significantly to the field of aging research because this model organism shows several hallmarks of aging that are common to humans (Guarente and Kenyon, 2000;Tatar et al, 2003).…”

Oxidative stress-associated rise of hepatic protein glycation increases inflammatory liver injury in uncoupling protein-2 deficient mice

“…57 It has been shown that sRAGE and F(ab) 2 fragments to block ligand binding to RAGE are capable of reducing an inflammatory response. 28,58 Therefore, we used recombinant RAGE, which functions as a decoy by binding RAGE ligands and prevents their interaction with extracellular RAGE by blocking the receptor.…”

Murine models of premature ageing for the study of diet-induced immune changes: improvement of leucocyte functions in two strains of old prematurely ageing mice by dietary supplementation with sulphur-containing antioxidants

“…In the cells of innate immunity, the phagocytic cells show functions that decrease with ageing and others that are over activated (2,(11)(12)(13) , whereas the anti-tumoral activity of natural killer (NK) cells, in most of the work, shows an age-related decrease (2,11,14) . In addition, it has been demonstrated that the competence of the immune system is an excellent marker of health (2,4,8,15,16) and several age-related changes in immune functions, such as low T-cell proliferative responses, IL-2 secretion and NK cell cytotoxicity, have been linked to longevity (2,15,16) . In previous studies, the earlier-mentioned functions and other immune functions, in lymphocytes and phagocytes, have been established as markers of biological age and therefore as predictors of longevity (2,13,16,17) .…”