scholarly journals Hypothalamus-Pituitary-Adrenal Hyperactivity in Human Aging Is Partially Refractory to Stimulation by Mineralocorticoid Receptor Blockade

2005 ◽  
Vol 90 (10) ◽  
pp. 5656-5662 ◽  
Author(s):  
Roberta Giordano ◽  
Mario Bo ◽  
Micaela Pellegrino ◽  
Marco Vezzari ◽  
Matteo Baldi ◽  
...  

Context: The hypothalamus-pituitary-adrenal (HPA) axis is mainly regulated by CRH, arginine vasopressin, and glucocorticoid feedback. Hippocampal mineralocorticoid receptors mediate proactive glucocorticoid feedback and mineralocorticoid antagonists, accordingly, stimulate HPA axis. Age-related HPA hyperactivity reflects impaired glucocorticoid feedback at the suprapituitary level. Design: ACTH, cortisol, and dehydroepiandrosterone (DHEA) secretion were studied in eight healthy elderly (75.1 ± 3.2 yr) and eight young (25.0 ± 4.6 yr) subjects during placebo or canrenoate (CAN) administration (200 mg iv bolus followed by 200 mg infused over 4 h). Results: During placebo administration, ACTH and cortisol areas under the curve (AUCs) in elderly subjects were higher than in young subjects (P ≤ 0.01); conversely, DHEA AUCs in elderly subjects were lower than in young subjects (P = 0.002). CAN increased ACTH, cortisol, and DHEA levels in both groups. In young subjects, ACTH, cortisol, and DHEA levels at the end of CAN infusion were higher (P ≤ 0.05) than after placebo. In elderly subjects, at the end of CAN infusion, ACTH, cortisol, and DHEA levels were higher (P = 0.01) than after placebo. Under CAN, ACTH and cortisol AUCs were persistently higher (P ≤ 0.01) and DHEA AUCs lower (P = 0.006) in elderly than in young subjects. Cortisol AUCs after CAN in young subjects did not become significantly different from those in elderly subjects after placebo. Conclusions: 1) Evening-time ACTH and cortisol secretion in elderly subjects is higher than in young subjects; 2) ACTH and cortisol secretion in elderly subjects is enhanced by CAN but less than that in young subjects; and 3) DHEA hyposecretion in elderly subjects is partially restored by mineralocorticoid antagonism. Age-related variations of HPA activity may be determined by some derangement in mineralocorticoid receptors function at the hippocampal level.

1994 ◽  
Vol 87 (3) ◽  
pp. 297-302 ◽  
Author(s):  
G. A. Ford ◽  
O. F. W. James

1. Cardiac chronotropic responses to isoprenaline are reduced with ageing in man. It is unclear whether this is due to reduced cardiac β-adrenergic sensitivity or to age-associated differences in reflex cardiovascular responses to the vasodilatory effects of isoprenaline. Age-associated changes in physical activity are also reported to influence β-adrenergic sensitivity. 2. The aim of the present study was to determine the contribution of alterations in reflex changes in parasympathetic and sympathetic influences and physical fitness to the age-associated reduction in cardiac chronotropic responses to β-adrenergic agonists. 3. The effect of ‘autonomic blockade’ with atropine (40 μg/kg intravenously) and clonidine (4 μg/kg intravenously) on blood pressure, heart rate and chronotropic responses to intravenous bolus isoprenaline doses was determined in eight healthy young (mean age 21 years), nine healthy elderly (72 years) and 10 endurance-trained elderly (69 years) subjects. 4. Elderly subjects had a reduced increase in heart rate after atropine (young, 49 ± 9 beats/min; elderly, 36 ± 5 beats/min; endurance-trained elderly, 34 ± 12 beats/min; P < 0.01) and did not demonstrate the transient increase in systolic blood pressure after clonidine observed in young subjects (young, 11 ± 10 mmHg; elderly, −12 ± 16 mmHg; endurance-trained elderly, −18 ± 11 mmHg; P < 0.01). 5. Cardiac chronotropic sensitivity to isoprenaline after ‘autonomic blockade’ increased in the young but decreased in the elderly subjects. The isoprenaline dose that increased heart rate by 25 beats/min before and after autonomic blockade' was: young, before 1.6 μg, after 2.8 μg, P < 0.01 (geometric mean, paired test); elderly, before 6.9 μg, after 3.6 μg, P < 0.05; endurance-trained elderly, before 5.9 μg, after 4.0 μg, P < 0.05. Cardiac chronotropic sensitivity to isoprenaline was significantly reduced in elderly compared with young subjects before (P < 0.01) but was similar after (P = 0.09) ‘autonomic blockade’. Chronotropic sensitivity did not differ between healthy and endurance-trained elderly subjects before or after ‘autonomic blockade’. 6. The age-associated reduction in cardiac chronotropic responses to bolus isoprenaline is primarily due to an age-related reduction in the influence of reflex cardiovascular responses on heart rate and not to an age-related reduction in cardiac β-adrenergic sensitivity. Endurance training is not associated with altered β-adrenergic chronotropic sensitivity in the elderly. The transient pressor response to intravenously administered clonidine may be lost in ageing man.


2009 ◽  
Vol 30 (1) ◽  
pp. 211-221 ◽  
Author(s):  
Fawzi Boumezbeur ◽  
Graeme F Mason ◽  
Robin A de Graaf ◽  
Kevin L Behar ◽  
Gary W Cline ◽  
...  

A decline in brain function is a characteristic feature of healthy aging; however, little is known about the biologic basis of this phenomenon. To determine whether there are alterations in brain mitochondrial metabolism associated with healthy aging, we combined 13C/1H magnetic resonance spectroscopy with infusions of [1-13C]glucose and [2-13C]acetate to quantitatively characterize rates of neuronal and astroglial tricarboxylic acid cycles, as well as neuroglial glutamate–glutamine cycling, in healthy elderly and young volunteers. Compared with young subjects, neuronal mitochondrial metabolism and glutamate–glutamine cycle flux was ∼30% lower in elderly subjects. The reduction in individual subjects correlated strongly with reductions in N-acetylaspartate and glutamate concentrations consistent with chronic reductions in brain mitochondrial function. In elderly subjects infused with [2-13C]acetate labeling of glutamine, C4 and C3 differed from that of the young subjects, indicating age-related changes in glial mitochondrial metabolism. Taken together, these studies show that healthy aging is associated with reduced neuronal mitochondrial metabolism and altered glial mitochondrial metabolism, which may in part be responsible for declines in brain function.


1988 ◽  
Vol 74 (3) ◽  
pp. 331-334 ◽  
Author(s):  
Scott L. Mader ◽  
Alan S. Robbins ◽  
Laurence Z. Rubenstein ◽  
Michael L. Tuck ◽  
Philip J. Scarpace

1. A number of age-related changes have been reported in the catecholamine–adrenoceptor–adenylate cyclase system. Most of the data available on these alterations come from resting subjects; the response to acute stress may provide additional insights into the age effect on these responses. 2. We measured supine and 10 min upright plasma noradrenaline and lymphocyte adenylate cyclase activity in ten healthy elderly subjects (age 66–80 years) and seven healthy young subjects (age 27–34 years). 3. Isoprenaline stimulation of lymphocyte adenylate cyclase activity was not significantly different between supine and upright positions or between elderly and young subjects. There was a marked increase in forskolin-stimulated adenylate cyclase activity in the upright posture in both elderly and young subjects. The increment over supine levels was 70% in the elderly (P < 0.025) and 73% in the young (P < 0.05). This enhanced forskolin activity was not seen in two young subjects who became syncopal. 4. These data suggest that enhanced forskolin-stimulated adenylate cyclase activity occurs after 10 min of upright posture in both elderly and young subjects, and may be relevant to immediate blood pressure regulation. We were unable to demonstrate any age-related differences in these acute adrenergic responses.


1993 ◽  
Vol 3 (7) ◽  
pp. 1371-1377
Author(s):  
D Fliser ◽  
M Zeier ◽  
R Nowack ◽  
E Ritz

The increase in GFR after an amino acid (AA) load, the so-called renal functional reserve, is impaired in the aged rat. Whether the renal functional reserve predicts the progression of renal disease in humans is controversial, but it is possible that age-related alterations of renal hemodynamics are relevant for the evolution of renal disease in the elderly. We compared renal hemodynamics before and after an AA infusion in 15 healthy normotensive subjects of young age (seven women, eight men; median age, 26 yr; range, 23 to 32) and in 10 subjects of old age (six women, four men; median age, 70 yr; range, 61 to 82) on normal dietary protein intake. Baseline GFR and effective RPF were measured after 12 h of fasting by the inulin (Cin) and para-aminohippurate (Cpah) steady-state infusion techniques. The renal functional reserve was examined after an overnight AA infusion (7% solution; 83 mL/h). Median basal Cin and Cpah were significantly lower (P < 0.01) in the elderly (102 and 339 mL/min per 1.73 m2) than in the young subjects (122 and 647 mL/min per 1.73 m2), but virtually all GFR values of the elderly were still within the normal range. Median Cin upon infusion of AA was 118 mL/min per 1.73 m2 (range, 98 to 137) in the elderly and 146 (range, 120 to 171) in the young, respectively. Corresponding values of Cpah were 349 mL/min per 1.73 m2 in the elderly versus 689 mL/min per 1.73 m2 in the young. Cin increased significantly (P < 0.01) after the AA load in both young and elderly subjects.(ABSTRACT TRUNCATED AT 250 WORDS)


Author(s):  
Sishir Mannava

Emotion recognition is an important aspect of social interaction. Deficits in emotion recognition have been tied to poor social competence, interpersonal functioning, and communication along with a reduced quality of life and inappropriate social behavior. Recent experimental evidence suggests that emotion recognition ability across modalities seems to change in an age-dependent way, with deficits specifically noted for negative emotion recognition. Therefore, the primary purpose of this study is to assess emotion recognition ability in both the visual and auditory modalities in healthy elderly patients versus healthy young patients to test the hypothesis that deficits in emotion recognition ability are age-related and increase with age across visual and auditory modalities. The secondary purpose of this study is to assess valence-specific emotion recognition ability to test the hypothesis that increased deficits for elderly individuals as compared to young healthy subjects occur for negative emotion recognition specifically. We examined the ability to recognize emotion in the auditory and visual modality in two groups of patients: healthy elderly subjects and healthy young subjects. The Montreal Affective Voices task (MAV), the Distorted Tunes task (DTT), the Awareness of Social Inference test (TASIT), and the Baron-Cohen Mind in the Eyes Test (EYES) were used to gauge emotion recognition ability. For the visual tasks (TASIT and EYES), the elderly subjects and young subjects did not have significant differences in performance. In addition, a significant difference was also not found for the DTT, indicating that both populations had intact lower-level auditory processing abilities. Significant differences were found between the two populations on the MAV task in both baseline accuracy and valence-specific performance. These findings suggest that age-related deficits in emotion recognition may be specific to the recognition of auditory emotion.


1995 ◽  
Vol 7 (3) ◽  
pp. 377-384 ◽  
Author(s):  
Sybille Rockstroh ◽  
Bruno Dietrich ◽  
Rolf Pokorny

The effects of training on two memory and two attention tasks were investigated in 24 healthy elderly and 23 young subjects. Two training periods, each consisting of four sessions, were performed, and the effects of training were assessed during two test sessions 1 week thereafter. Significant age-related effects at the pretraining test session were found for reaction times to a simple visual stimulus, retrieval time of information from long-term storage, and the speed of focusing attention. In both age groups, performance of the first two tasks was significantly improved by training; however, the age-related effect remained significant after training. In the focused attention task, the age difference at baseline disappeared after training due to an opposite learning trend in young and elderly subjects. Thus, the cognitive performance of elderly subjects could be trained to a large extent. Significant age differences, however, could be decreased only if the test performance of young subjects did not improve.


Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2235
Author(s):  
Alyann Otrante ◽  
Amal Trigui ◽  
Roua Walha ◽  
Hicham Berrougui ◽  
Tamas Fulop ◽  
...  

High-density lipoproteins (HDL) maintain cholesterol homeostasis through the role they play in regulating reverse cholesterol transport (RCT), a process by which excess cholesterol is transported back to the liver for elimination. However, RCT can be altered in the presence of cardiovascular risk factors, such as aging, which contributes to the increase in the incidence of cardiovascular diseases (CVD). The present study was aimed at investigating the effect of extra virgin olive oil (EVOO) intake on the cholesterol efflux capacity (CEC) of HDL, and to elucidate on the mechanisms by which EVOO intake improves the anti-atherogenic activity of HDL. A total of 84 healthy women and men were enrolled and were distributed, according to age, into two groups: 27 young (31.81 ± 6.79 years) and 57 elderly (70.72 ± 5.6 years) subjects. The subjects in both groups were given 25 mL/d of extra virgin olive oil (EVOO) for 12 weeks. CEC was measured using J774 macrophages radiolabeled with tritiated cholesterol ((3H) cholesterol). HDL subclass distributions were analyzed using the Quantimetrix Lipoprint® system. The HDL from the elderly subjects exhibited a lower level of CEC, at 11.12% (p < 0.0001), than the HDL from the young subjects. The CEC of the elderly subjects returned to normal levels following 12 weeks of EVOO intake. An analysis of the distribution of HDL subclasses showed that HDL from the elderly subjects were composed of lower levels of large HDL (L-HDL) (p < 0.03) and higher levels of small HDL (S-HDL) (p < 0.002) compared to HDL from the young subjects. A multiple linear regression analysis revealed a positive correlation between CEC and L-HDL levels (r = 0.35 and p < 0.001) as well as an inverse correlation between CEC and S-HDL levels (r = −0.27 and p < 0.01). This correlation remained significant even when several variables, including age, sex, and BMI as well as low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and glucose levels (β = 0.28, p < 0.002, and β = 0.24, p = 0.01) were accounted for. Consuming EVOO for 12 weeks modulated the age-related difference in the distribution of HDL subclasses by reducing the level of S-HDL and increasing the level of intermediate-HDL/large-HDL (I-HDL/L-HDL) in the elderly subjects. The age-related alteration of the CEC of HDL was due, in part, to an alteration in the distribution of HDL subclasses. A diet enriched in EVOO improved the functionality of HDL through an increase in I-HDL/L-HDL and a decrease in S-HDL.


1983 ◽  
Vol 65 (2) ◽  
pp. 155-157 ◽  
Author(s):  
T. G. Cotter ◽  
K. O'Malley

1. Neutrophils from drug-free elderly subjects produced approximately 50% less cyclic AMP in response to isoprenaline than did neutrophils from young subjects. A significant difference in basal cyclic AMP levels was also evident (elderly 2.8 ± 0.37; young 4.9 ± 0.36 pmol of cAMP/107 cells; P < 0.05). 2. With a range of anti-neutrophil monoclonal antibodies no evidence of age-related neutrophil population heterogeneity was found. 3. These findings indicate that the age-related decline in β-adrenoceptor responsiveness is not due to changes in the neutrophil population. 4. The present results support the hypothesis that there is a generalized decline in β-adrenoceptor-mediated responsiveness in the elderly.


1999 ◽  
Vol 9 (3) ◽  
pp. 197-205
Author(s):  
L.L. Borger ◽  
S.L. Whitney ◽  
M.S. Redfern ◽  
J.M. Furman

Postural sway during stance has been found to be sensitive to moving visual scenes in young adults, children, and those with vestibular disease. The effect of visual environments on balance in elderly individuals is relatively unknown. The purpose of this study was to compare postural sway responses of healthy elderly to those of young subjects when both groups were exposed to a moving visual scene. Peak to peak, root mean squared, and mean velocity of the center of pressure were analyzed under conditions combining four moving scene amplitudes ( 2 . 5 ∘ , 5 ∘ , 7 . 5 ∘ , 10 ∘ ) and two frequencies of scene movement (0.1 Hz, 0.25 Hz). Each visual condition was tested with a fixed floor and sway referenced platform. Results showed that elderly subjects swayed more than younger subjects when experiencing a moving visual scene under all conditions. The elderly were affected more than the young by sway referencing the platform. The differences between the two age groups were greater at increased amplitudes of scene movement. These results suggest that elderly are more influenced by dynamic visual information for balance than the young, particularly when cues from the ankles are altered.


1993 ◽  
Vol 102 (7) ◽  
pp. 508-517 ◽  
Author(s):  
Neil T. Shepard ◽  
Albert Schultz ◽  
Mian Ju Gu ◽  
Neil B. Alexander ◽  
Thomas Boismier

The use of dynamic posturography (EquiTest) for the characterization of postural control biomechanics would be aided by specific knowledge of what the measured data imply about body segment movements. To investigate this issue, the biomechanics of a group of 15 healthy elderly subjects were compared to those of healthy young subjects by using both dynamic posturography and a laboratory movement and force measuring system. The results from EquiTest were analyzed by 1) routine clinical interpretation of data and 2) a clinical research interpretation by subjecting the EquiTest parameters to additional statistical comparison of mean performance of the young and elderly groups. The young-elderly differences from the 2 EquiTest analyses were then compared to the young-elderly differences derived from the laboratory protocol. The routine clinical interpretation of EquiTest data identified the same increases in sway shown by the laboratory study, but did not reveal the more subtle differences indicated by the laboratory study. When the EquiTest data were subjected to additional statistical analysis, the characterization of difference between young and elderly subjects was the same as that of the laboratory study, with the exception of issues of head versus trunk movement, a measure not made by EquiTest. This essential similarity in the characterization of elderly compared to young subjects by both systems suggests 1) that EquiTest is able to detect subtle differences in biomechanics of postural control between young and elderly healthy adult groups and 2) that implied movements of center of gravity, trunk versus lower limbs, and strength of reaction measures are consistently detected by both EquiTest and the laboratory kinematics and dynamics measurement systems.


Sign in / Sign up

Export Citation Format

Share Document