Age-associated changes in rat plasma lipids, platelet fatty acids and prostacyclin release

The effect of age on plasma lipids, platelet fatty acids and prostacyclin release was studied in the rat. The contents of arachidonic acid, cholesterol, bile acids and free fatty acids in the plasma of aged rats (15 months old) were higher than those of young rats (3 months old). No significant differences in fatty acid composition of platelet lipids and release of prostacyclin from aortas between young and aged rats were observed. The data suggest that plasma lipids may play a more important role in the development of cardiovascular disease with increasing age than prostaglandins do.     

Effect of microgravity on plasma catecholamine responses to stressors during space flight

The effect of microgravity on the sympathicoadrenal system (SAS) activity in humans and animals has not yet been clarified. Our previous studies suggested that the SAS activity, evaluated by circulating and/or urinary catecholamine (CA) levels in astronauts during space flights, was found to be rather unchanged. However, CA levels were measured in astronauts only at rest conditions. The aim of the present study was to investigate effect of microgravity during space flight and post-flight readaptation on responsiveness of the SAS to somatic and psychic stressors evaluated by levels of catecholamines and their metabolite in the blood of the Slovak cosmonaut during his stay on board the space station Mir.     

Beta-blockade with intrinsic sympathetic activity modifies favorably exercise-induced changes in plasma lipoproteins

The effects of beta-blockade on acute exercise-induced changes in plasma lipoprotein levels were investigated in 12 healthy normotensive subjects by use of beta-blockers of three types: a nonselective agent, a beta 1-selective agent, and a nonselective agent with intrinsic sympathomimetic activity (ISA) or partial agonist activity. Each subject received each drug and a placebo for 1 wk each according to a randomized double-blind crossover design. After placebo, exercise caused 10-20% increases in total plasma cholesterol and the high-density lipoprotein (HDL)-cholesterol fraction. The total-to-HDL cholesterol ratio fell, particularly during the 30-min recovery phase. Pindolol treatment increased resting values of HDL cholesterol (from 43 +/- 4 to 48 +/- 4 mg/dl) and potentiated the response to exercise (to 59 +/- 5 vs. 51 +/- 4 mg/dl after placebo). The total-to-HDL cholesterol ratio was significantly lower after pindolol treatment than after placebo. In contrast, neither atenolol nor timolol affected exercise-induced changes in plasma lipoprotein levels. The effects of pindolol on other study parameters (exercise endurance and exercise-induced increases in systolic blood pressure, heart rate, and potassium) were similar to the effects of the nonselective agent, timolol. We conclude that the effects of pindolol on the plasma lipid profile are due to its ISA and that the process activated (possibly plasma lecithin-cholesterol acyltransferase activity) is under minimal sympathetic control and, therefore, sensitive to the expression of ISA both at rest and in response to exercise.     

Differential plasma catecholamine and neuropeptide Y responses to acute stress in rats

Neuropeptide Y (NPY) is a vasoconstrictor present in the sympatho-adrenomedullary system and may be co-released with norepinephrine (NE) and epinephrine (EPI) during sympathetic activation. We studied plasma NPY-immunoreactivity (-ir, radioimmunoassay) and catecholamine (radioenzymatic) responses during two acute stress paradigms that differ in character, intensity, and duration. The intermittent stress of footshock (0.75 and 1.5 mA, 0.5 sec duration, at 5-sec intervals, for 5 min) evoked intensity-dependent immediate increments in plasma NE and EPI, and a delayed NPY-ir response (+0.6 +/- 0.1 pmol/ml). Prolonged (60 min) immobilization caused greater increases in plasma NE and EPI levels and no changes in plasma NPY-ir until the end of the stress session (+0.3 +/- 0.1 pmol/ml). Plasma NPY-ir responses correlated with those of NE but not with EPI suggesting a sympathetic origin for the release of the peptide. Relatively greater NPY-ir responses to footshock than to immobilization may be consistent with a preferential release of the peptide by a bursting but not continuous mode of sympathetic activation. However, it may also be due to a differential activation of the sympathetic nerves and adrenal medulla by these two stress situations.     

Cardiovascular, metabolic and plasma catecholamine responses to passive and active exercises.

Eight healthy male volunteers (aged 19.6+/-3.0 years) were submitted to the unloaded active (AE) and passive (PE) cycling exercise-tests performed on an adapted cycle ergometer at a pedalling rate of 50 rpm. Intensity of active exercise was about 10% of VO2 max. In the PE exercise test the ergometer was moved electrically. During both tests the systolic time intervals (STI), stroke volume (SV), heart rate (HR), blood pressure (BP), oxygen uptake (VO2), rating of perceived exertion (RPE), electrical muscle activity (EMG), plasma adrenaline (A), noradrenaline (NE) and blood lactate (LA) concentrations were measured. Exercise induced changes in VO2, RPE and EMG were significantly higher during AE than PE. Shortening of the pre-ejection period (PEP) and diminishing of the PEP to ejection time (ET) ratio were similar in both types of exercise, whereas HR increased only during AE. A significant increase in cardiac output (p<0.01) resulted from increased SV (p<0.01) during PE and from increased HR (p <0.01) during AE. MAP increased only during PE and it was higher than at rest and during AE (p<0.01). Absence of changes in SV and MAP during AE may be considered as a secondary effect of the decrease in TPR. Plasma catecholamines did not increase above resting values in either type of exercise. Blood LA concentration increased during both PE and AE but it reached higher values (p<0.01) after the latter test. The present data suggest that the inotropic state depends on the mechanoreflexes originated in skeletal muscles. However, contribution of changes in preload to shortening of PEP can not be excluded.     

Blood pressure and plasma catecholamine responses to various challenges during exercise-recovery in man

The purpose of this study was to assess the effects of a 2 h cycle exercise (50% VO2max) on heart rate (HR) and blood pressure (BP), and on plasma epinephrine (E) and norepinephrine (NE) concentrations, during the recovery period in seven normotensive subjects. Measurements were made at rest in supine (20 min) and standing (10 min) positions, during isometric exercise (hand-grip, 3 min, 25% maximal voluntary, contraction), in response to a mild psychosocial challenge (Stroop conflicting color word task) and during a 5-min period of light exercise (42 +/- 3% VO2max). Data were compared to measurements taken on another occasion under similar experimental conditions, without a previous exercise bout (control). The results showed HR to be slightly elevated in all conditions following the exercise bout. However, diastolic and systolic BP during the recovery period following exercise were not significantly different from the values observed in the control situation. Plasma NE concentrations in supine position and in response to the various physiological and/or psychosocial challenges were similar in the control situation and during the recovery period following exercise. On the other hand plasma E (nmol.1-1) was about 50% lower at rest (0.11 +/- 0.03 vs 0.23 +/- 0.04) as well as in response to hand-grip (0.21 +/- 0.04 vs 0.41 +/- 0.20) and the Stroop-test (0.21 +/- 0.05 vs 0.41 +/- 0.15) following the exercise bout.(ABSTRACT TRUNCATED AT 250 WORDS)     

Age-associated changes in plasma testosterone levels in male mice and their relation to social dominance or subordinance

Plasma testosterone (T) levels were determined in male mice of the CD-1 (ICR) strain from 30 to 680 days of age. The mean plasma T was 5.2 ± 1.0 ng/ml for adult male mice (70–400 days old, 102 mice) and 1.8 ± 0.9 ng/ml for old males (450–680 days old, 11 mice). Through 140 determinations, the highest T value obtained was 52.3 ng/ml in an 80-day-old individual while the lowest was 0.08 ng/ml in a 680-day-old animal. It was found that plasma T was significantly decreased in the old age, although individual variation in T levels was considerable. On the other hand, social dominance or subordinance was examined among male mice in each cage and its relation to plasma T was investigated. Dominance or subordinance was verified by frequency of chases or attacks delivered or received, or number of fights won or lost. It was observed that dominant-subordinate relationships were present in 6 out of 10 cages and that the dominant individual had a significantly higher T level than the subordinate male; the mean T level was 10.5 ± 2.5 ng/ml for the dominant individuals vs 2.2 ± 0.8 ng/ml for the subordinate ones. Marked individual variation in plasma T titers in male mice seems to be related to the dominance/subordinance rank within a group.     

Quercetin's influence on exercise-induced changes in plasma cytokines and muscle and leukocyte cytokine mRNA.

Trained male cyclists (n = 40) ingested quercetin (Q; n = 20) (1,000 mg/day) or placebo (P; n = 20) supplements under randomized, double-blinded methods for 3 wk before and during a 3-day period in which subjects cycled for 3 h/day at approximately 57% maximal work rate. Blood samples were collected before and after each exercise session and assayed for plasma IL-6, IL-10, IL-1ra, IL-8, TNF-alpha, and monocyte chemoattractant protein 1, and leukocyte IL-10, IL-8, and IL-1ra mRNA. Muscle biopsies were obtained before and after the first and third exercise sessions and assayed for NF-kappaB and cyclooxygenase-2 (COX-2), IL-6, IL-8, IL-1beta, and TNF-alpha mRNA. Postexercise increases in plasma cytokines did not differ between groups, but the pattern of change over the 3-day exercise period tended to be lower in Q vs. P for IL-8 and TNF-alpha (P = 0.094 for both). mRNA increased significantly postexercise for each cytokine measured in blood leukocyte and muscle samples. Leukocyte IL-8 and IL-10 mRNA were significantly reduced in Q vs. P (interaction effects, P = 0.019 and 0.012, respectively) with no other leukocyte or muscle mRNA group differences. Muscle NF-kappaB did not increase postexercise and did not differ between Q and P. Muscle COX-2 mRNA increased significantly postexercise but did not differ between Q and P. In summary, 1 g/day quercetin supplementation by trained cyclists over a 24-day period diminished postexercise expression of leukocyte IL-8 and IL-10 mRNA, indicating that elevated plasma quercetin levels exerted some effects within the blood compartment. Quercetin did not, however, influence any of the muscle measures, including NF-kappaB content, cytokine mRNA, or COX-2 mRNA expression across a 3-day intensified exercise period.     

Prolonged changes in plasma concentrations of catecholamine metabolites following a single infusion of an MPTP analog

The magnitude and duration of effects of a single intravenous injection of 4'-amino MPTP, an analogue of the dopamine neurotoxin, MPTP, on plasma levels of catechols and normetanephrine were examined in conscious dogs. Plasma samples were collected prior to treatment with intravenous saline or 4'-amino MPTP.2HCl (22.5 mg/kg) and at weekly intervals for six weeks following treatment. Saline treatment had no effect on plasma levels of any of the measured compounds. Following 4'-amino MPTP, plasma DHPG fell to 14% of the pre-injection value and remained decreased for the full 6-week test period, with partial recovery by week 6 to 42% of the pre-injection value. Plasma DOPAC levels fell to 28% of pre-injection values 1 week after treatment with 4'-amino MPTP and showed no evidence of recovery during the 6-week test period. Plasma DOPA fell to 58% of the pre-injection level, while concentrations of the catecholamines NE, EPI, and DA were generally unaffected. The plasma concentration of the O-methylated NE metabolite, normetanephrine, was also unchanged by 4'-amino MPTP treatment. There were no differences in the concentrations of DA, NE or EPI within the adrenal medulla between saline and 4'-amino MPTP treated groups. This pattern of changes in plasma levels of catechols, which is consistent with presynaptic inhibition of MAO within sympathetic terminals, may be a useful indicator of exposure to MPTP-like neurotoxins.     

Age-associated changes in central nervous system glycerolipid composition and metabolism

In this review, changes in brain lipid composition and metabolism due to aging are outlined. The most striking changes in cerebral cortex and cerebellum lipid composition involve an increase in acidic phospholipid synthesis. The most important changes with respect to fatty acyl composition involve a decreased content in polyunsaturated fatty acids (20:4n-6, 22:4n-6, 22:6n-3) and an increased content in monounsaturated fatty acids (18:1n-9 and 20:1n-9), mainly in ethanolamine and serineglycerophospholipids. Changes in the activity of the enzymes modifying the phospholipid headgroup occur during aging. Serine incorporation into phosphatidylserine through base-exchange reactions and phosphatidylcholine synthesis through phosphatidylethanolamine methylation increases in the aged brain. Phosphatidate phosphohydrolase and phospholipase D activities are also altered in the aged brain thus producing changes in the lipid second messengers diacylglycerol and phosphatidic acid.     

Age-associated analysis of oxidative stress parameters in human plasma and erythrocytes

Oxidative damage accumulation in macromolecules has been considered as a cause of cellular damage and pathology. Rarely, the oxidative stress parameters in healthy humans related to the individual age have been reported. The purpose of this study was to examine the redox status in plasma and erythrocytes of healthy individuals and determine correlations between these parameters and the aging process. The following parameters were used: malondialdehyde (MDA), protein carbonyls (PCO), 4-hydroxy-2,3-trans-nonenal (HNE), reduced glutathione (GSH), glutathione disulfide (GSSG) and uric acid (UA) in blood and plasma samples of 194 healthy women and men of ages ranging from 18 to 84 years. The results indicate that the balance of oxidant and antioxidant systems in plasma shifts in favor of accelerated oxidation during ageing. That is demonstrated by increases of MDA, HNE, GSSG and by the slight decrease of erythrocytic GSH with age. As the content of UA is more determined by metabolic and nutritional influences than by the balance between prooxidants and antioxidants there was no significant age-related change observed. For plasma concentrations of HNE the first time age-dependent reference values for healthy humans are presented.     

Age-associated changes in the estrogen receptor-active proteases of female rabbit liver

Female rabbit liver cytosol contains a receptor-modifying activity that converts the 250,000 estrogen receptor of liver and uterine cytosol to a 37,000 form. There is an age-dependent increase in this receptor-active protease and in the general protease activity of rabbit liver cytosol, measured with [14C]casein. Sephacryl S-200 chromatography of liver cytosol shows that in the young animal (5 weeks old) the major receptor-modifying activity elutes near the void volume, while in the older animal (13 weeks old) activities having lower molecular weights are present. The general protease activity elution profile is similar to the receptor-active protease profile for the 5-week-old rabbit but not the 13-week-old rabbit. The liver cytosol of the older animal has a high molecular weight protease active toward [14C]casein but not toward the estrogen receptor. The changes in the estrogen receptor forms and the receptor-modifying activity profiles of liver cytosol that occur during development in the rabbit suggest that receptor-modifying activity may initially be associated with the estrogen receptor to form a high molecular weight complex.     

The repertoire diversity and magnitude of antibody responses to bacterial antigens in aged mice: I. Age-associated changes in antibody responses differ according to the mouse strain

Aging influences the host immune responses in various ways. In aging mice we have studied the antibody responses to two unrelated bacterial antigens. Streptococcus pneumoniae R36a vaccine (Pn) and TNP coupled to Brucella abortus (TNP-BA). Aged animals (20-24 months old) of the C57BL/6 strain had markedly reduced numbers of IgM antibody plaque-forming cells (PFC) to Pn as compared to young/adult mice (2-3 months old). In contrast, the anti-Pn IgM PFC responses of aged BALB/c mice were consistently higher than they were in the young/adult mice. The increased anti-Pn responses were not due to a nonspecific immunostimulation, because the responses of aged BALB/c mice to TNP-BA were lower as compared to the adults. However, the aged BALB/c mice responded relatively poorly to Pn challenge, and their IgG responses (as determined by ELISA plaque assay) demonstrated a very high individual variability. The clonotypic diversity of anti-Pn response in young BALB/c and C57BL/6 is limited, such that the majority of PFC produce antibody that express all idiotopes (Id) of the T15 immunoglobulin encoded in the VH-S107/Vk22 genes. In contrast, the PFC from aged mice are diverse, expressing incomplete T15 Id or none at all, suggesting that the antibodies are encoded by altered T15 genes and by different, non-T15 genes. Our data demonstrate that the age-related changes in the magnitude of antibody response to certain antigens are influenced by the host genetic make-up, and that the changes in magnitude and diversity of antibody response may be unrelated to each other.