Impact of age on cortisol secretory dynamics basally and as driven by nutrient-withdrawal stress

The present study tests the clinical hypothesis that aging impairs homeosta tic adaptations of cortisol secretion to stress. To this end, we implemente d a short-term 3.5-day fast as an ethically acceptable metabolic stressor i n eight young (ages 18-35 yr) and eight older (ages 60-72 yr) healthy men. Volunteers were studied in randomly ordered fed vs, fasting sessions. To ca pture the more complex dynamics of cortisol's feedback control, blood was s ampled every 10 min for 24 h for later RIA of serum cortisol concentrations and quantitation of the pulsatile, entropic, and 24-h rhythmic modes of co rtisol release using deconvolution analysis, the approximate entropy statis tic, and cosine regression, respectively. The stress of fasting elevated th e mean (24-h) serum cortisol concentration equivalently in the two age coho rts [i.e. from 7.2 +/- 0.35 to 11.6 +/- 0.71 mu g/dL, in young men and from 7.7 +/- 0.39 to 12.6 +/- 0.59 mu g/dL in older individuals (P < 10(-7))]. The rise in integrated cortisol output was driven mechanistically by select ive augmentation of cortisol secretory burst mass (P = 0.002). The resultan t daily (pulsatile) cortisol secretion rate increased significantly but equ ally in young (from 94 +/- 6.3 to 151 +/- 15 mu g/dL . day) and older (from 85 +/- 5.4 to 145 +/- 7.3 mu g/dL.day) volunteers (P < 10(-4)). Nutrient r estriction also prompted a marked reduction in the quantifiable regularity of (univariate) cortisol release patterns in both cohorts (P < 10-4). Howev er, older men showed loss of joint synchrony of cortisol and LH secretion e ven in the fed state, which failed to change with metabolic stress (P < 10( -6)). In addition, older individuals maintained a premature (early-day) cor tisol elevation in the fed state and unexpectedly evolved an anomalous furt her cortisol phase advance of 99 +/- 16 min during fasting (P < 10(-5)). Ca loric deprivation in aging men also disproportionately elevated the mesor o f 24-h rhythmic cortisol release (P = 10(-7)) and elicited a greater increm ent in the mean day-night variation in cortisol secretory-burst mass (P < 0 .01 vs. young controls). Lastly, short-term caloric depletion in older subj ects paradoxically normalized their age-associated suppression of the 24-h rhythm in cortisol interburst intervals. In summary, acute metabolic stress in healthy aging men (compared with youn g individuals) unmasks distinct, albeit complex, disruption of cortisol hom eostasis. These dynamic anomalies impact the feedback-dependent and time-se nsitive coupling of pulsatile and 24-h rhythmic cortisol secretion. Nutrien t-withdrawal stress in the older male heightens the cortisol phase disparit y already evident in fed elderly individuals. Conversely, the stress of fas ting in young men paradoxically reproduces selected features of the aging u nstressed (fed) cortisol axis; viz., abrogation of joint cortisol-LH synchr ony and suppression of the normal diurnal variation in cortisol burst frequ ency. Whether fasting would unveil analogous disruption of feedback-depende nt control of the corticotropic axis in healthy aging women is not yet know n.