Strategies for reversing age-related sympathetic neuropathy loss in immune organs

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.