An introduction to neuroimmunomodulation and aging.

gerontologists. Accordingly, this special issue of Neuroimmunomodulation provides an opportunity to review progress in this field of research. An introductory article presented by De la Fuente reviews the most widely accepted theories of aging, especially the oxidation-inflammation theory, and how the neuroimmune communication is impaired with age. Moreover, she proposes that dysregulation of the immune system, in the context of the neuroimmune network, may contribute to the chronic oxidative stress that underlies aging. Additional work reviews the fundamental concepts of the immunosenescence field, including remodeling changes of the immune system and inflammaging (see Ostan et al.). This work also reviews the role of the polymorphism of several genes involved in the immune response and inflammation in centenarians. The centenarians are the best example of successful aging, since they have avoided major age-related pathologies and are equipped with a well-preserved and efficient immune system. Preliminary data suggest that centenarians have increased plasma stress hormones (CRH, ACTH and cortisol) but show similar monocyte migration towards a bacterial chemotactic product (f-MLP) or neuropeptides when compared to young adults (see Genedani et al.). Two papers review the concept that chronic psychological stress may premature the aging of neuroendocrine Aging is associated with gradual remodeling changes in various if not all systems in our body. During the last 50 years, several theories have been put forward to explain aging, including the free radical, neuroendocrine and immunological theories. Recently, accumulating evidence suggests that changes in the communication between major allostatic systems, including the immune and nervous systems (and concomitant loss of homeostasis and resistance to stress), is one of the fundamental causes of physiological senescence. However, it is difficult to find out whether with age neural changes induce immunological changes or whether an impaired immune system induces nervous changes, or whether both processes occur simultaneously, which is the most likely mechanism according to some authors. The clinical consequences of the impaired communication between the immune and neuroendocrine systems may include increased susceptibility to infectious diseases, neoplasias and autoimmune disease. However, this altered morbidity is not evenly distributed and might be influenced by external or epigenetic factors, including psychological stress. Indeed, recent evidence suggests that psychological distress and stress factors are not only involved in immunosenescence but can also be associated with premature aging. Therefore, interventions aimed to ameliorate the changes in the neuroimmune communication during aging would be of special interest for the Published online: November 26, 2008