Cognitive and Behavioral Consequences of Impaired Immunoregulation in Aging

Abstract

A hallmark of the aged immune system is impaired immunoregulation of the innate and adaptive immune system in the periphery and also in the central nervous system (CNS). Impaired immunoregulation may predispose older individuals to an increased frequency of peripheral infections with concomitant cognitive and behavioral complications. Thus, normal aging is hypothesized to alter the highly coordinated interactions between the immune system and the brain. In support of this notion, mounting evidence in rodent models indicate that the increased inflammatory status of the brain is associated with increased reactivity of microglia, the innate immune cells of the CNS. Understanding how immunity is affected with age is important because CNS immune cells play an integral role in propagating inflammatory signals that are initiated in the periphery. Increased reactivity of microglia sets the stage for an exaggerated inflammatory cytokine response following activation of the peripheral innate immune system that is paralleled by prolonged sickness, depressive-like complications and cognitive impairment. Moreover, amplified neuroinflammation negatively affects several aspects of neural plasticity (e.g., neurogenesis, long-term potentiation, and dendritic morphology) that can contribute to the severity of neurological complications. The purpose of this review is to discuss several key peripheral and central immune changes that impair the coordinated response between the immune system and the brain and result in behavioral and cognitive deficits.

Aging alters the immunological response to ischemic stroke

“…As we did not directly examine non-irradiated mice, interpretation of our results may be confounded by differences in the ability of young and old mice to recover from irradiation. This is unlikely as the rejuvenation (i.e., Young → Old) and age-acceleration (i.e., Old → Young) patterns pertaining to brain production of cytokines and growth factors [57, 76], microglia phagocytosis [65], locomotor activity and coordination [23, 24], emotional behavior [13, 27, 87], and other features of frailty [49] are highly consistent with the literature in aging research. Despite these findings, it is worth noting that significant interactions between age and irradiation in microglia activation have been demonstrated by others [36, 45, 73].…”

Synergistic Increase of Oxidative Stress and Tumor Markers in PAH-Exposed Workers

“…Age with an increase in the risk of TNF-α levels was marginal (P=0.055, OR=0.47, 95% CI: 0.21-1.02). In fact, a dysregulation of the innate and adaptive immune system is hypothesized as a prominent key player in the aging process which is accompanied by increased inflammatory cytokines, in particular TNF-a (Corona et al, 2011). Since no differences were found in the distributions of age in the present study, further investigations are required to confirm the association in individuals with a significant distribution of age.…”

Dietary Luteolin Reduces Proinflammatory Microglia in the Brain of Senescent Mice

“…5,[21][22][23][24] Although evidence indicates that luteolin is an immunomodulator that may be effective in reducing age-related inflammation, 10 whether ingesting a diet supplemented with luteolin reduces brain microglial cell activity had not been examined before. The important results show that providing mice a diet supplemented with luteolin inhibited increases in brain microglial cell activity and proinflammatory cytokine production in aged mice and after stimulation of the peripheral immune system in adult mice.…”