Affiliations: Department of Human Anatomy and Pathology, Loma Linda University, School of Medicine, Loma Linda, USA | Department of Psychology, Kent State University and The Kent Summa Initiative for Clinical and Translational Research, Summa Health System, Akron, OH, USA
Note: [] Correspondence to: Denise L. Bellinger, Ph.D., Department of Pathology and Human Anatomy, Loma Linda University School of Medicine, 11021 Campus Street, AH 325, Loma Linda, CA 92350, USA. Tel.: +1 909 558 7069; Fax: +1 909 558 0432; E-mail: dbellinger@llu.edu
Abstract: The sympathetic nervous system (SNS) regulates innate and adaptive immunity via sympathetic innervation of lymphoid organs. In aging, immune functions decline that are characterized by thymic involution, inefficient antigen presentation, impaired lymphocyte function, and inflammaging. Immunosenescence leads to increased frequency of infectious diseases, cancer and autoimmunity in the elderly. Concomitant with immunosenescence, sympathetic thymic nerves are preserved, but sympathetic neuropathy develops in secondary lymphoid organs, like the spleen. These phenomena may be causally linked to affect health. In this review, we discuss changing sympathetic-immune cross-talk in aging, shared cellular mechanisms for sympathetic neuroaxonal dystrophy (NAD) and central neurodegenerative diseases, and present strategies for delaying/reversing/preventing age-induced sympathetic dysfunction in immune organs. Further research is needed to understand the interplay and temporal relationships between immunosenescence and NAD in aging sympathetic neurons. Models of aging strongly suggest the importance of genetics (epigenetic and nuclear and mitochondrial DNA mutations), neuroendocrine and growth factors, stress, and behavior (diet and exercise) in determining the influence of aging on neural-immune decline. Successfully restoring sympathetic innervation of secondary immune organs by direct or indirect methods has important implications for host resistance to immune-mediated and/or metabolic diseases, vaccine efficacy, and overall health and well-being across a diverse elderly population.
