Age-Related Alterations in Autonomic Nervous System Innervation of Lymphoid Tissue

Abstract

Complex bidirectional signaling occurs between the nervous and immune systems that impacts the functions of both systems. In response to stressors, the central nervous system has modulatory effects on the immune system through release of hormones, paracrine signals, and by direct contacts between nerves and immune cells. Conversely, in response to antigens and pathogens, immune system activation results in production of cytokines that induce altered neural activity. Progressive age‐related decline in brain and immune functions in the elderly results in impaired cognition, reestablishment of homeostasis at age‐ adjusted set points, and immune senescence. This chapter reviews our understanding of how normal aging alters the cross talk between the autonomic nervous system and the immune system to alter immune functions with age. Changes in the relationship between noradrenergic (NA) nerves and immune cells with age have been demonstrated, including altered density and compartmentation of NA nerves in lymphoid organs, norepinephrine (NE) turnover, density and coupling of adrenergic receptors, and availability and functional capacity of target lymphoid cells. Strain‐dependent changes in how NA nerves age in secondary lymphoid tissue have been reported. These changes alter nerve‐to‐immune signaling, and subsequently immune functions in old rodents. These findings suggest that impaired sympathetic regulation of immune function occurs in aged individuals, which may contribute to the increase in susceptibility to infectious diseases, autoimmunity, and cancer in the elderly. Age‐related changes in sympathetic nervous system (SNS) modulation of immune functions are likely to contribute to the reduced immunocompetence observed in clinical studies with elderly subjects. Understanding the age‐related changes that occur in SNS modulation of immune functions could be useful for developing novel strategies for treating diseases, disease prevention, and improving overall health in the elderly. List of Abbreviations: aMNE, a‐methylnorepinephrine; Con A, concanavalin A; CGRP, calcitonin gene‐related peptide; CRH, corticotropin‐releasing hormone; DN, dual negative; DP, dual positive; GM‐ CFU, granulocyte/macrophage colony‐forming units; IFN‐g, interferon‐g; MAO‐B, monoamine oxidase B; MHC, major histocompatibility complex; NA, noradrenergic; NE, norepinephrine; NGF, nerve growth factor; NPY, neuropeptide Y; PALS, periarteriolar lymphatic sheath; SCID, severe combined immunodeficiency; 6‐OHDA, 6‐hydroxydopamine; SNS, sympathetic nervous system; SP, single positive; TH, tyrosine hydroxylase; VIP, vasoactive intestinal polypeptide; SOD, superoxide dismutase