Aging and Alterated Sympathetic Innervation
A study published in Journal of Neuroimmunology suggests that aging is linked to significant alterations in the sympathetic nervous innervation of lymphoid organs that may contribute to aging-related immunosuppression,
The sympathetic nervous system (SNS) is a major branch of the autonomic nervous system and the peripheral stress system. The function of the human SNS is altered by aging, and these changes involve both the properties of the adrenergic receptors and the outflow of sympathetic neural traffic to individual organs.
Recent evidence indicates that progressive sympathetic (noradrenergic) activation occurs with aging. This involves sympathetic outflow to the heart, skeletal muscle vasculature, the gut and liver, but excludes the kidneys, and is accompanied by reduced adrenal medullary secretion of epinephrine (Murray Esler et al., Am J Physiol Regulatory Integrative Comp Physiol 282:R909, 2002). The nature of the underlying disturbance in central nervous system (CNS) sympathetic control, however, remains unknown.
Previous research in cardiac failure and essential hypertension indicates the importance of projections of noradrenergic neurons to the forebrain in generating the peripheral sympathetic nervous stimulation present. In the Am J Physiol Regulatory Integrative Comp Physiol study, mentioned above, the authors report that the sympathetic activity accompanying aging to be associated with increased suprabulbar subcortical turnover of norepinephrine.
As discussed by the lowered epinephrine secretion rate with aging, accompanied by sympathetic nervous system activation, emphasizes that the two elements of the “sympathoadrenal medullary system” do not always act in concert, so that a mismatching of sympathetic activity and epinephrine secretion rate can occur. Two other examples, of several, are the increased epinephrine secretion accompanying sympathetic inhibition that is present in both fasting and vasovagal syncope. Whether any functional disability is conveyed by reduced epinephrine secretion in the elderly is not clear.
Previous studies also indicate that sympathetic (noradrenergic) nerve fibers in primary and secondary lymphoid organs undergo age associated alterations in their density, distribution in the parenchyma, norepinephrine (NE) concentrations, NE uptake and release, and beta-adrenergic receptor-induced signaling in rodents. Specifically, thymic involution is associated with increased noradrenergic nerve fiber density and NE concentration, while there is a decline in noradrenergic neuronal density and NE concentrations in spleen and lymph nodes in male rats and mice.
In the Journal of Neuroimmunology study Srinivasan ThyagaRajan and colleagues from Loma Linda University School of Medicine, Loma Linda, California, report that the density of sympathetic (noradrenergic) nerve fibers increased significantly in all the compartments of thymuses but especially in the cortex and paracortex, associated with a reduced tissue volume and an increase in NE concentration in aged female Fischer 344 rats.
However, sympathetic innervation and NE levels declined in spleen and mesenteric lymph nodes, and was accompanied by significant reductions in NK cell activity, IL-2 and IFN-gamma production, and T and B cell proliferation in older female rats.
These results demonstrating an age-related reduction in the immune responses, including mitogen-induced proliferation and cytokine production, and NK cell activity in spleens from female rats are in accordance with previous studies on aging in female rodents.
The rapid decline in sympathetic innervation of secondary lymphoid organs in female rats is consistent with the loss of sympathetic (noradrenergic) innervation previously reported in male rats that had grown older. According to the authors this may indicate the presence of age-related sympathetic peripheral neuropathy, associated with an increase in the NE turnover and impairment in beta-adrenergic receptor signal transduction in these lymphoid organs.
In conclusion, it is known that immunosuppression is a characteristic feature of the aging process, leading to increased risk for autoimmunity, cancer and infectious diseases. The results from the present study demonstrate that the reduction in immune responses in aged female rats are associated with a decline in sympathetic NA innervation in the secondary lymphoid organs, spleen and MLN, and an apparent increase in NA innervation in the thymus due to age-associated thymic involution.
These observations in rodents, and the human data mentioned above suggest that alterations in sympathetic (noradrenergic) innervation, SNS activity and outflow, and the sympathetic-immune interface may be causally involved and implicated in a variety of cardiovascular disorders, certain types of autoimmune diseases, cancer, infections, and Alzheimer’s disease, for all of which incidence rises with age.
SOURCE: J Neuroimmunol 2011, 233:54. Epub 2010 Dec 24.
