Human ageing and the sympathoadrenal system
Abstract
Over the past three decades the changes in sympathoadrenal function that occur with age in healthy adult humans have been systematically studied using a combination of neurochemical, neurophysiological and haemodynamic experimental approaches. The available experimental evidence indicates that tonic whole-body sympathetic nervous system (SNS) activity increases with age. The elevations in SNS activity appear to be region specific, targeting skeletal muscle and the gut, but not obviously the kidney. The SNS tone of the heart is increased, although this appears to be due in part to reduced neuronal reuptake of noradrenaline (norepinephrine). In contrast to SNS activity, tonic adrenaline (epinephrine) secretion from the adrenal medulla is markedly reduced with age. This is not reflected in plasma adrenaline concentrations because of reduced plasma clearance. Despite widely held beliefs to the contrary, sympathoadrenal responsiveness to acute stress is not exaggerated with age in healthy adults. Indeed, adrenaline release in response to acute stress is substantially attenuated in older men. The mechanisms underlying the age-associated increases in SNS activity have not been established, but our preliminary data are consistent with increased subcortical central nervous system (CNS) sympathetic drive. These changes in sympathoadrenal function with advancing age may have a number of important physiological and pathophysiological consequences for human health and disease.
The sympathetic nervous system (SNS) plays a critical role in the maintenance of physiological homeostasis in general, and arterial blood pressure in particular, under basal (resting) conditions and in response to acute stress. Post-ganglionic sympathetic neurons innervating the heart and resistance vessels help control cardiac output, arterial blood pressure and regional vascular conductance, thus ensuring the proper perfusion of vital organs. SNS stimulation of adrenaline (epinephrine) release from the adrenal medulla contributes importantly to the regulation of cardiovascular function as well as energy metabolism. The SNS also has a key role in the regulation of internal body temperature. In addition to these normal physiological interactions, the SNS has been implicated in a number of common clinical disorders including hypertension, congestive heart failure, sudden cardiac death, the insulin resistance (metabolic) syndrome and obesity.
Adult human ageing is associated with a number of important changes in physiological function and regulation to which the SNS may contribute (Rowe & Troen, 1980; Folkow & Svanborg, 1993; Lakatta, 1993; Seals, 1993). Moreover, the incidence of many chronic disease states, including those mentioned above, increases with advancing age (Biermann & Ross, 1977; DeFronzo, 1979; Schoenberger, 1986; Folkow & Svanborg, 1993; Lakatta, 1993). The changes in the sympathoadrenal system that occur with primary ageing in adult humans, and how such changes may impact important physiological and pathophysiological processes, have been systematically investigated by our laboratories and others over the past three decades. This topical review discusses some of the key experimental observations in the area of human ageing and sympathoadrenal function during this period. The review focuses on the results of studies using neurochemical and/or neurophysiological (microneurographical recordings) measures of sympathoadrenal system function. Investigations utilizing measurements derived from spectral analysis of cardiovascular variability are not included because of the difficulty in properly interpreting such results. For additional information on this topic the reader is referred to prior reviews by the authors and others (Rowe & Troen, 1980; Linares & Halter, 1987; Roberts & Tumer, 1987; Esler et al. 1989; Docherty, 1990; Seals, 1993; Seals et al. 1994; Esler, 1995).
Acknowledgments
The work from the laboratory of Professor Seals cited in this review was supported by National Institutes of Health award AG06537. Professor Seals wishes to acknowledge the important contributions of trainees and/or colleagues Robin Callister, Kevin Davy, Frank Dinenno, Pamela Parker Jones, Mary Beth Monroe, Alexander Ng, Mary Jo Reiling, Hirofumi Tanaka and J. Andrew Taylor. The work from the laboratory of Professor Esler cited in this review was supported in part by an institute grant from the National Health and Medical Research Council of Australia to the Baker Medical Research Institute, and in part by National Institutes of Health award AG06537 (USA). Professor Esler wishes to acknowledge the important contributions of his colleagues David Kaye, Gavin Lambert, Gary Jennings, Mario Vaz, Claudia Ferrier and Graeme Eisenhofer.