Reduced epinephrine clearance and glycemic sensitivity to epinephrine in older individuals

1998 ◽  
Vol 275 (5) ◽  
pp. E770-E776 ◽  
Author(s):  
James C. Marker ◽  
William E. Clutter ◽  
Philip E. Cryer
Keyword(s):  
Sedentary Lifestyle ◽  
Plasma Norepinephrine ◽  
Older Individuals ◽  
Plasma Epinephrine ◽  
Response Curves ◽  
Older Subjects ◽  
Young Subjects ◽  
Cellular Responsiveness ◽  
The Impact ◽  
Epinephrine Concentration

To test the hypothesis that glycemic sensitivity to epinephrine is reduced in older individuals and to assess the impact of a sedentary lifestyle on responses to the hormone, we performed 30-min sequential intravenous infusions of epinephrine (0, 41, 82, 164, 246, and 328 pmol ⋅ kg−1⋅ min−1) in young ( n = 10) and older ( n = 23) healthy subjects. We performed these again after 12 mo of physical training, which raised peak O2consumption from 24.4 ± 1.0 to 30.4 ± 1.4 ml ⋅ kg−1⋅ min−1( P < 0.01) in most of the older subjects ( n = 21). During epinephrine infusions, plasma epinephrine concentrations were higher ( P = 0.0001) in older than in young subjects (e.g., final values of 7,280 ± 500 vs. 4,560 ± 380 pmol/l, respectively), indicating that the clearance of epinephrine from the circulation was reduced in the older individuals. Plasma epinephrine concentration-response curves disclosed reduced glycemic sensitivity to the hormone in the older subjects ( P = 0.0001), a finding plausibly attributed to increased sympathetic neural activity, as evidenced here by higher plasma norepinephrine concentrations ( P = 0.0001) in the older subjects and consequent desensitization of cellular responsiveness to catecholamines. Training did not correct reduced epinephrine clearance, reduced glycemic sensitivity to epinephrine, or raised norepinephrine levels. We conclude that aging is associated with reduced clearance of epinephrine from the circulation and reduced glycemic sensitivity to epinephrine, the latter plausibly attributed to an age-associated increase in sympathetic neural norepinephrine release. These age-associated changes are not the result of a sedentary lifestyle.

Effect of physical training on the capacity to secrete epinephrine

1988 ◽  
Vol 64 (1) ◽  
pp. 11-16 ◽  
Author(s):  
M. Kjaer ◽  
H. Galbo
Keyword(s):  
Hypobaric Hypoxia ◽  
Plasma Norepinephrine ◽  
Plasma Epinephrine ◽  
O2 Uptake ◽  
Acute Hypobaric Hypoxia ◽  
Arterial Pco2 ◽  
Norepinephrine Concentration ◽  
Arterial Po2 ◽  
Secretory Capacity ◽  
Epinephrine Concentration

Epinephrine responses to hypoglycemia and to identical relative work loads have been shown to be higher in endurance-trained athletes than in untrained subjects. To test the hypothesis that training increases the adrenal medullary secretory capacity, we studied the effects of glucagon (1 mg/70 kg iv), acute hypercapnia (inspired O2 fraction = 7%), and acute hypobaric hypoxia (inspired Po2 = 87 Torr), respectively, on the epinephrine concentration in arterialized hand vein blood in eight endurance-trained athletes [T, O2 uptake = 66 (62-70) ml.min-1.kg-1] and seven sedentary males [C, O2 uptake = 46 (41-50)]. In response to identical increments in glucagon concentrations, plasma epinephrine increased more in T than in C subjects [0.87 +/- 0.11 vs. 0.38 +/- 0.14 (SE) nmol/l, P less than 0.05]. In response to hypercapnia [arterial PCO2 = 56 +/- 0.7 Torr (T) and 55 +/- 0.4 (C), P greater than 0.05], the increment in epinephrine was significant in T (0.38 +/- 0.11 nmol/l) but not (P less than 0.1) in C subjects (0.22 +/- 0.11). Hypoxia [arterial PO2 = 42 +/- 2 Torr (T) and 41 +/- 2 (C), P greater than 0.05] increased epinephrine in T (0.22 +/- 0.10 nmol/l, P less than 0.05) but not in C subjects (0.01 +/- 0.07). The plasma norepinephrine concentration never changed, whereas heart rate always increased, the increase being higher (P less than 0.05) in T than in C subjects only during hypercapnia. The results indicate that training increases the capacity to secrete epinephrine.

Doublet Discharges in Motoneurons of Young and Older Adults

2006 ◽  
Vol 95 (5) ◽  
pp. 2787-2795 ◽  
Author(s):  
Anita Christie ◽  
Gary Kamen
Keyword(s):  
Firing Rate ◽  
Motor Unit ◽  
Force Production ◽  
Motor Units ◽  
Voluntary Contraction ◽  
Older Individuals ◽  
Motor Unit Firing ◽  
Older Subjects ◽  
Young Subjects ◽  
Ramp Contractions

The purpose of this study was to investigate the occurrence of motor unit doublet discharges in young and older individuals at different rates of increasing force. Participants included eight young (21.9 ± 3.56 yr) and eight older (74.1 ± 8.79 yr) individuals, with equal numbers of males and females in each group. Motor unit activity was recorded from the tibialis anterior during isometric dorsiflexion using a four-wire needle electrode. Subjects performed three ramp contractions from zero to 50% maximal voluntary contraction (MVC) force at each of three rates: 10, 30, and 50% MVC/s. Overall, the occurrence of doublets was significantly higher in the young than in the older individuals. However, neither group showed differences in the occurrence of doublets across the three rates of force production. Doublet firings were observed in 45.6 (young) and 35.1% (old) of motor units at 10% MVC/s; 48.6 (young) and 22.5% (old) of motor units at 30% MVC/s; and 48.4 (young) and 31.4% (old) at 50% MVC/s. The maximal firing rate was significantly higher and the force at which the motor units were recruited was significantly lower for those units that fired doublets than those that did not. The force at which doublets occurred ranged from 3.42 to 50% MVC in the young subjects and from 0 (force onset) to 50% MVC in the older subjects. The results of this study suggest that the occurrence of doublets is dependent on both motor unit firing rate and force level. The lower incidence of doublets in older individuals may be attributable to changes in the intrinsic properties of the motoneurons with aging, which appear to play a role in doublet discharges.

Modulatory Effects of Levodopa on Cognitive Control in Young but not in Older Subjects: A Pharmacological fMRI Study

2011 ◽  
Vol 23 (10) ◽  
pp. 2797-2810 ◽  
Author(s):  
Özgür A. Onur ◽  
Martina Piefke ◽  
Chuh-Hyoun Lie ◽  
Christiane M. Thiel ◽  
Gereon R. Fink
Keyword(s):  
Age Groups ◽  
Older Individuals ◽  
Interference Control ◽  
Double Blind ◽  
Older Volunteers ◽  
Visual Spatial ◽  
Older Subjects ◽  
Young Subjects ◽  
Spatial Interference ◽  
Effects Of Aging

Older individuals show decline of prefrontal cortex (PFC) functions which may be related to altered dopaminergic neurotransmission. We investigated the effects of aging and dopaminergic stimulation in 15 young and 13 older healthy subjects on the neural correlates of interference control using fMRI. In a double-blind, placebo-controlled within-subject design, subjects were measured after levodopa (100 mg) or placebo administration. In each session, subjects performed a visual–spatial interference task based on a Stroop/Simon-like paradigm. Across age groups, interference (incongruent relative to congruent trials) was associated with activations in the presupplementary motor area, ACC, and intraparietal cortex. Increased interference was found behaviorally in older volunteers. Differential activation in left dorsolateral PFC in young subjects and bilateral PFC activity in older subjects was observed to be associated with interference control. Performance deteriorated under levodopa only in young subjects. This was accompanied by an increase of neural activity in ACC (p < .05; small-volume correction for multiple comparisons). Worsening of performance under levodopa in young subjects and the associated effect on ACC may indicate that overstimulation of the dopaminergic system compromises interference control. This supports the inverted-U-shaped model of neurotransmitter action.

scholarly journals Effect of Exogenous Cholecystokinin (CCK)-8 on Food Intake and Plasma CCK, Leptin, and Insulin Concentrations in Older and Young Adults: Evidence for Increased CCK Activity as a Cause of the Anorexia of Aging

2001 ◽  
Vol 86 (12) ◽  
pp. 5830-5837 ◽  
Author(s):  
Caroline G. MacIntosh ◽  
John E. Morley ◽  
Judith Wishart ◽  
Howard Morris ◽  
Jan B. M. J. Jansen ◽  
...  
Keyword(s):  
Food Intake ◽  
Older People ◽  
Healthy Aging ◽  
Protein Energy Malnutrition ◽  
Age Groups ◽  
Postprandial Glucose ◽  
Saline Control ◽  
Older Subjects ◽  
Young Subjects ◽  
The Impact

Healthy aging is associated with reductions in appetite and food intake—the so-called anorexia of aging, which may predispose to protein-energy malnutrition. One possible cause of the anorexia of aging is an increased satiating effect of cholecystokinin (CCK). To investigate the impact of aging on the satiating effects of CCK, 12 young and 12 older healthy subjects received 25-min iv infusions of saline (control) and CCK-8, 1 ng/kg per min or 3 ng/k per min, on 3 separate days before a test meal. Older subjects ate less than young subjects, and food intake was suppressed 21.6% by CCK-8, compared with the control day (P &lt; 0.05). The suppression of energy intake by CCK-8 in older subjects was twice that in young subjects (32 ± 6% vs. 16 ± 6% sem, P &lt; 0.05) and was related to plasma CCK-8 concentrations, which were higher at baseline (P &lt; 0.05) and increased more during CCK-8 infusions in older than young subjects (P &lt; 0.01). The extent of suppression of food intake per given rise in plasma CCK-8 concentrations did not differ between the two age groups (P = 0.35). Endogenous CCK concentrations were higher at baseline in older subjects (P &lt; 0.001) and decreased during the CCK-8 but not control infusions (P &lt; 0.01), suggesting that CCK suppresses its own release. Plasma leptin concentrations were not affected by CCK infusion, whereas postprandial insulin concentrations were lowered and the peak postprandial glucose concentration was delayed but not affected by CCK-8 infusion. Because older people retain their sensitivity to the satiating effects of exogenous CCK and plasma endogenous CCK concentrations are higher in older people, increased CCK activity may contribute to the anorexia of aging.

The human sympathochromaffin system

1984 ◽  
Vol 247 (3) ◽  
pp. E380-E384 ◽  
Author(s):  
S. D. Shah ◽  
T. F. Tse ◽  
W. E. Clutter ◽  
P. E. Cryer
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Plasma Norepinephrine ◽  
Plasma Epinephrine ◽  
Norepinephrine Release ◽  
Norepinephrine Concentration ◽  
Sympathetic Nervous ◽  
Biological Actions ◽  
Chromaffin Tissue ◽  
Epinephrine Concentration

Hypoglycemia stimulates adrenomedullary epinephrine secretion; standing stimulates sympathetic neural norepinephrine release. In five bilaterally adrenalectomized persons plasma epinephrine, measured with a sensitive single-isotope derivative assay, rose from 15 +/- 2 to 35 +/- 7 pg/ml (P less than 0.02) during hypoglycemia but did not increase during standing. In contrast, plasma norepinephrine rose during standing but not during hypoglycemia. Thus, in humans 1) extra-adrenal epinephrine secretion is regulated and derived from innervated cells other than sympathetic postganglionic neurons; 2) because the plasma levels of epinephrine in adrenalectomized individuals even in response to the potent stimulus of hypoglycemia are below physiological thresholds, any biological actions of extra-adrenal epinephrine in adults must be paracrine rather than endocrine in nature; 3) hypoglycemia does not appear to stimulate the sympathetic nervous system. In view of these findings, we propose that extra-CNS catecholamine-producing tissues be termed the sympathochromaffin system consisting of two components: 1) the sympathetic nervous system that releases the neurotransmitter norepinephrine from its postganglionic neurons, and 2) the chromaffin tissues, including the adrenal medullae, that contain cells that secrete epinephrine, norepinephrine, or dopamine. The plasma epinephrine concentration is a valid measure of its chromaffin tissue (predominantly adrenomedullary) secretion, whereas the plasma norepinephrine concentration is an index of sympathetic neuronal activity under some but not all conditions.

ENDEMIC GOITRE IN THAILAND

1966 ◽  
Vol 34 (1) ◽  
pp. 23-39 ◽  
Author(s):  
ALICE DIMITRIADOU ◽  
ROMSAI SUWANIK ◽  
T. RUSSELL FRASER ◽  
J. D. PEARSON
Keyword(s):  
Discharge Rate ◽  
Iodine Concentration ◽  
Endemic Goitre ◽  
Older Individuals ◽  
Total Iodine ◽  
Hormone Synthesis ◽  
Rapid Formation ◽  
Iodine Metabolism ◽  
Older Subjects ◽  
Young Subjects

SUMMARY (1) In a village in the endemic-goitre area in Thailand, studies of the iodine metabolism (127I as well as 131I, and including chromatographic analysis of thyroid biopsy digests) have been made on 35 subjects sampled particularly from the younger decades. (2) The high 24-hr. uptake of 131I by the thyroid was correlated inversely with the urinary 127I-iodide excretion; the [131I]thyroid discharge rate was very rapid in the diffuse goitres of young subjects, less so in the older subjects with nodular goitres, and was not rendered normal by a previous iodide repletion. (3) Thyroid biopsy studies on some of these subjects showed: (a) in the three diffuse endemic goitres of young subjects studied, low iodine concentrations, rapid formation of [131I]iodothyronines, a normal MIT:DIT ratio (< 1) and a normal distribution of 127I-iodoaminoacids; (b) in two nodular endemic goitres in older individuals total iodine concentration was similarly low, but the rate of formation of [131I]iodothyronines was very slow, the MIT:DIT ratio high (> 1), and the 127I-iodoaminoacids stored consisted preponderantly of iodotyrosines, as found also in twenty sporadic goitres in Londoners. (4) These findings suggest that hormone synthesis was normal and rapid in the diffuse endemic goitres of the young subjects, but defective in the nodular endemic goitres of older subjects, as was also found in sporadic goitres.

Enhanced thermogenic response to epinephrine after 48-h starvation in humans

1990 ◽  
Vol 258 (1) ◽  
pp. R87-R93 ◽  
Author(s):  
P. I. Mansell ◽  
I. W. Fellows ◽  
I. A. Macdonald
Keyword(s):  
Metabolic Rate ◽  
Resting Metabolic Rate ◽  
Normal Weight ◽  
Base Line ◽  
Glycerol Concentration ◽  
Plasma Epinephrine ◽  
Epinephrine Infusion ◽  
Fed State ◽  
Young Subjects ◽  
Epinephrine Concentration

The effects of 48-h starvation on the physiological responses to a 30-min infusion of epinephrine at 25 ng.min-1.kg body wt-1 were studied in 11 normal-weight healthy young subjects. Starvation led to considerable alterations in basal metabolism including a significant (mean 3.6%) increase in resting metabolic rate. During the infusions, plasma epinephrine concentration rose less in the starved state (+1.47 nmol/l) than in the normally fed state (+1.73 nmol/l) (SE 0.06 nmol/l; P less than 0.05). The maximum increments (mean +/- SE) in heart rate induced by epinephrine were 11.9 +/- 1.3 beats/min in the normally fed state and 20.1 +/- 2.0 beats/min in the starved state (P less than 0.001); the corresponding mean increments in blood glycerol concentration were 0.07 and 0.14 mmol/l (SE 0.01 mmol/l; P less than 0.01). The increase in the metabolic rate above base line during the final 10 min of the epinephrine infusion was 0.58 +/- 0.18 kJ/min in the normally fed state and 0.78 +/- 0.14 kJ/min in the starved state (P less than 0.01). The chronotropic, lipolytic, and thermogenic effects of infused epinephrine were therefore enhanced by prior starvation, despite the lower plasma epinephrine levels.

scholarly journals The Impact of SARS-CoV-2 (COVID-19) and its Lockdown Measures on the Mental and Functional Health of Older Individuals

2021 ◽  
Author(s):  
Maria Chiara Fastame ◽  
Ilaria Mulas ◽  
Valeria Putzu ◽  
Gesuina Asoni ◽  
Daniela Viale ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Wearable Sensors ◽  
Well Being ◽  
Functional Health ◽  
Cognitive Deterioration ◽  
Older Individuals ◽  
Physical And Mental Health ◽  
Psychological Well Being ◽  
The Impact ◽  
Healthy Participants

AbstractThe effect of the COVID-19 on the physical and mental health of Italian older individuals displaying signs of cognitive deterioration has not been deeply investigated. This longitudinal study examined the impact of COVID-19 lockdown measures on the psychological well-being and motor efficiency of a sample of Italian community-dwellers with and without cognitive decline. Forty-seven participants underwent instrumental gait analysis performed in ecological setting using wearable sensors, and completed a battery of tasks assessing cognitive functioning and psychological well-being, before and after the full lockdown due to the COVID-19 spreading. A series of Multivariate Analyses of Variance (MANOVAs) documented that the superior gait performance of the cognitively healthy participants exhibited before the COVID-19 spread, vanished when they were tested at the end of the lockdown period. Moreover, before the outbreak of the COVID-19, cognitively healthy participants and those with signs of cognitive decline reported similar levels of psychological well-being, whereas, after the lockdown, the former group reported better coping, emotional competencies, and general well-being than the participants displaying signs of cognitive decline. In conclusion, the full COVID-19 outbreak had a significant impact on the mental and motor functioning of older individuals with and without signs of cognitive deterioration living in Italy.

scholarly journals Vaccine responses in ageing and chronic viral infection

2021 ◽  
Author(s):  
Chloe Rees-Spear ◽  
Laura E McCoy
Keyword(s):  
Viral Infections ◽  
The Elderly ◽  
People Living With Hiv ◽  
Chronic Infections ◽  
Vaccine Responses ◽  
Inflammatory Conditions ◽  
Immunological Changes ◽  
Cellular Responsiveness ◽  
Living With Hiv ◽  
The Impact

Abstract Lay Summary Improved life expectancy in recent years has led to a growing population of adults over the age of 60. Age is commonly associated with increased inflammatory conditions and infections. Similar immunological changes have been observed during chronic infections, in particular HIV, where this is compounded by the success of antiretroviral therapy that has increased the number of people living with HIV into their sixties and beyond. The increased susceptibility of these groups to infection makes vaccination all the more important. However, the alterations to their immune systems call into question how effective those vaccinations may be. Here we discuss vaccine efficacy within elderly and chronically infected populations and investigate the immunological changes that may impact vaccine responsiveness. Over the last few decades, changing population demographics have shown that there is a growing number of individuals living past the age of 60. With this expanding older population comes an increase in individuals that are more susceptible to chronic illness and disease. An important part of maintaining health in this population is through prophylactic vaccination, however, there is growing evidence that vaccines may be less effective in the elderly. Furthermore, with the success of anti-viral therapies, chronic infections such as HIV are becoming increasingly prevalent in older populations and present a relatively unstudied population with respect to the efficacy of vaccination. Here we will examine the evidence for age-associated reduction in antibody and cellular responsiveness to a variety of common vaccines, and investigate the underlying causes attributed to this phenomenon, such as inflammation and senescence. We will also discuss the impact of chronic viral infections on immune responses in both young and elderly patients, particularly those living with HIV, and how this affects vaccinations in these populations.

scholarly journals β-Adrenergically Stimulated Fat Oxidation Is Diminished in Middle-Aged Compared to Young Subjects*

1999 ◽  
Vol 84 (10) ◽  
pp. 3764-3769
Author(s):  
E. E. Blaak ◽  
M. A. van Baak ◽  
W. H. M. Saris
Keyword(s):  
Skeletal Muscle ◽  
Energy Expenditure ◽  
Total Energy ◽  
Fat Oxidation ◽  
Substrate Utilization ◽  
Total Energy Expenditure ◽  
Adrenergic Stimulation ◽  
Middle Aged ◽  
Older Subjects ◽  
Young Subjects

Abstract The effect of aging on β-adrenergically mediated substrate utilization was investigated in nine young (25.2 ± 1.7 yr old) and eight older males (52.9 ± 2.1 yr old), matched for body weight and body composition. In a first experiment, the nonselectiveβ -agonist isoprenaline (ISO) was infused in increasing standardized doses, and during each infusion period energy expenditure and substrate utilization were determined by indirect calorimetry. In a second experiment, forearm skeletal muscle metabolism was studied during a standardized infusion dose of ISO (19 ng/kg fat-free mass·min). During β-adrenergic stimulation there was an increased carbohydrate oxidation (at an ISO infusion dose of 24 ng/kg fat-free mass·min, 31% vs. 21% of total energy expenditure; P &lt; 0.05) and a decreased fat oxidation (51 vs. 62 of total energy expenditure; P &lt; 0.05) in older compared to young subjects. Skeletal muscle lactate release significantly increased in the older subjects (from −175 ± 32 to −366 ± 66 nmol/100 mL forearm tissue·min), whereas there was no change in young subjects (from− 32 ± 21 to 23 ± 57 nmol/100 mL forearm tissue·min; interaction group × ISO, P &lt; 0.01). Additionally, there was a tendency toward a blunted ISO-induced increase in nonesterified fatty acid uptake in the older subjects (interaction group × ISO, P = 0.062). Thus, middle-aged subjects have a blunted ability to oxidize fat during β-adrenergic stimulation compared to young subjects. This diminished fat oxidation may be an important etiological factor in the age-related increase in body fatness and obesity by favoring fat storage above oxidation.

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