Models of Aging of Neuroimmunomodulation: Strategies for Its Improvement

Abstract

Communication between the nervous and the immune systems suffers impairment with aging, which explains the altered homeostasis and the resulting increase of morbidity and mortality in aged subjects. In humans, rats and specially in mice, we have proposed several models to study this fact. The established models of premature aging have been mice and humans with poor response to stress and anxiety versus subjects of the same chronological age without that characteristic, isolation, males versus females, menopausal models (in rodents after ovariectomy) and obesity. In all cases, the prematurely aged animals suffer an alteration of the nervous system (shown by behavioral tests) and immunosenescence as well as oxidative and inflammatory stress, which is followed by early mortality. In addition, in the above-mentioned models and in normal chronological aging, we have observed the effect of several lifestyle strategies, such as ingestion of adequate amounts of antioxidants, performance of moderate physical exercise, and different kinds of environmental enrichment, which improve the function of the immune cells and their redox state as well as animal behavior. Therefore, they retard the aging process and seem to increase the longevity of the individuals.

Gender-Specific Neuroimmunoendocrine Response to Treadmill Exercise in 3xTg-AD Mice

“…In this work, the weight of thymus was used as an indirect indicator of immunological functional state, with involution of thymus showing a correlation with differences in immunological function [39] and immunological aging [40]. As expected, the total weight of thymus was higher in females than in males, and this gender difference was more obvious when its relative weight was considered, suggesting a better immune function in the female gender.…”

Chronic Stress Exacerbates Tau Pathology, Neurodegeneration, and Cognitive Performance through a Corticotropin-Releasing Factor Receptor-Dependent Mechanism in a Transgenic Mouse Model of Tauopathy

“…Further, aged and diseased brains are more sensitive to stress effects and seem unable to adapt to the continued presence of a stressor (Buchanan et al, 2008). While these conditions are usually associated with excessive microglia activation, it is also possible that aging, disease and/or stress may suppress microglia activation depending on concentration, timing and duration (acute vs. chronic) of the stressor (Glezer and Rivest, 2004; Sorrells and Sapolsky, 2007; Dhabhar, 2009), a phenomenon that has been described in human brains (De la Fuente and Gimenez-Llort, 2010). Future studies designed to measure levels of cytokines such as interleukin IL-1β, IL-6 and tumor necrosis factor-α, as well as M1 and M2 macrophage markers, would help clarify these issues.…”

Peripheral immune system and neuroimmune communication impairment in a mouse model of Alzheimer's disease

“…1). The difficulty in preserving the homeostasis is the basis of the increase of age‐related morbidity and mortality 2,6,7 . With aging, the nervous system suffers a progressive loss of function, which can be shown, for example, in such functions as sensation, cognition, memory, and motor activity.…”