Middle-aged Control Group Research Articles

Oxidative stress on mitochondrial antioxidant defense system in the aging process: Role of dl-α-lipoic acid and l-carnitine

Background Oxidative damage is hypothesized to accumulate throughout the lifetime of an organism, eventually giving rise to aging. The mitochondria may be the primary cellular source and target of endogenous ROS as they are produced as a normal byproduct of the electron transport system. Methods Male albino Wistar rats were used in this study. The animals were divided into 6 groups, each group consisting of 6 animals. Groups I, III, and V were young, middle-aged and aged control rats and Groups II, IV, and VI were treated with carnitine (300 mg/kg bw) and dl-α-lipoic acid (150 mg/kg bw), respectively. After the treatment period, the animals were sacrificed and the heart and skeletal muscle were removed for analysis. Result There was a significant reduction in the levels of antioxidants in both middle-aged and aged rats whereas the thiobarbituric acid reactive substances were found to be increased. Co-supplementation of carnitine and lipoic acid improved the antioxidant status and brought down the levels of TBARS. Conclusion Co-supplementation of lipoic acid with carnitine has a beneficial effect in reversing the age-related abnormalities seen in aging. This effect was associated with the decrease in free radical production and rise in antioxidant levels by carnitine and lipoic acid, thereby lowering oxidative stress.

Correlation of Cochlear Blood Supply with Mitochondrial DNA Common Deletion in Presbyacusis

ObjectivesTo study the relationships between cochlear hypoxia, mitochondrial (mt) DNA4977 deletion and metabolic features of mtDNA in presbyacusis.Material and MethodsSixty-seven temporal bones from a presbyacusis group, an age-matched control group and a young and middle-aged control group were involved in the experiment. Nested and tri-nested polymerase chain reactions (PCRs) were applied to test for the presence of the mtDNA4977 deletion. Computer imaging processing was used to measure blood vessel parameters in the internal acoustic meatus (IAM).ResultsThe mtDNA4977 deletion was detected in 17/34 ears in the presbyacusis group, 4/19 ears in the age-matched control group and 0/14 ears in the young and middle-aged control group. In the presbyacusis group, the lumen of the vasa nervorum of the IAM showed a more severe narrowing in cases with than without the mtDNA4977 deletion.ConclusionsThe high incidence of the mtDNA4977 deletion in the temporal bones of presbyacusis patients suggests a correlation between the mtDNA4977 deletion and presbyacusis. Hypoxia of the cochlea may cause the mtDNA4977 deletion and other mtDNA mutants and furthermore may cause a reduction in mitochondrial oxidative phosphorylation and decreased function of the acoustic neural system. The symptoms of presbyacusis may occur when the function of the acoustic neural system is impaired as a result of abnormal mtDNA metabolism reaching a particular threshold.

Biochemical and molecular biological aspects of glucose intolerance in elderly persons

Changes in carbohydrate metabolism in elderly persons have drawn considerable attention but the findings from different studies are in contrast and are even controversial. The insulin receptors in erythrocytes were studied in elderly euglycaemic patients and in a middle-aged control group. The examined persons were also subjected to measurements of blood glucose, insulin and C-peptide concentrations, before and 3 hours after a dietetic meal. In the present study it was found that in spite of the maintained insulin level and C-peptide secretion, some structural and corresponding changes in membrane insulin receptors and the binding site caused differences in postreceptor responses in elderly persons. The examined groups, consisted of 29 males, average age of 66 years (65-70), with normal serum glucose level and 19 middle-aged males, average age of 42 years (32-48), with normal glycoregulation. In basal condition, elderly persons have both normal morning serum insulin (19.68 ? 4.00 mU/L) and C-peptide (2.04 ? 0.78 nmol/L) level. In elderly persons, the number of high affinity insulin receptors in erythrocytes membrane is 22.80 ? 6.18 but the formed insulin-high affinity receptors were not stable. Dissociation constant (Kd1) indicates its elevated dissociation (0.11 ? 0.04). At the same time the number of insulin low affinity binding sites is increased (13 273 ? 5 572) with a fast dissociation of the hormone (13.99 ? 3.37). Food intake raised the number of high affinity receptors compared to the basal value. Alteration in insulin binding affinity suggests the structural and corresponding changes in membrane receptors that may cause differences in postreceptors responses in elderly persons.

A disturbance in the neuronal insulin receptor signal transduction in sporadic Alzheimer's disease.

Disturbances of glucose and energy metabolism are hypothesized as pathogenetic factors in sporadic dementia of Alzheimer type (SDAT). Insulin and is receptors play an important role in the regulation of brain glucose metabolism and neuronal growth. In postmortem brain cortex in SDAT, the densities of brain insulin receptors were decreased compared to adult controls, but were increased in relation to aged controls. Tyrosine kinase activity, a signal transduction mechanism common to insulin and IGF-1 receptors, was reduced in SDAT in comparison to middle-aged and age-matched control groups. The data are consistent with a neurotrophic role of insulin in the human brain and an upregulation of insulin receptors is SDAT brain as a compensatory mechanism, possibly due to impaired signal transduction mechanism.

Brain insulin and insulin receptors in aging and sporadic Alzheimer's disease.

The search for the causes of neurodegenerative disorders is a major theme in brain research. Acquired disturbances of several aspects of cellular metabolism appear pathologically important in sporadic Alzheimer's disease (SDAT). Among these brain glucose utilisation is reduced in the early stages of the disease and the regulatory enzymes important for glucose metabolism are reduced. In the brain, insulin, insulin-like growth factors and their receptors regulate glucose metabolism and promote neuronal growth. To detect changes in the functional activity of the brain insulin neuromodulatory system of SDAT patients, we determined the concentrations of insulin and c-peptide as well as insulin receptor binding and IGF-I receptor binding in several regions of postmortem brain cortex during aging and Alzheimer's disease. Additionally, we performed immunohistochemical staining with antibodies against insulin in neocortical brain areas in SDAT and controls. We show for the first time that insulin and c-peptide concentration in the brain are correlated and decrease with aging, as do brain insulin receptor densities. Weak insulin-immunoreactivity could be demonstrated histochemically in pyramidal neurons of controls, whereas in SDAT a stronger insulin-immunoreactivity was found. On a biochemical level, insulin and c-peptide levels were reduced compared to middle-aged controls, but were unchanged compared to age-matched controls. Brain insulin receptor densities in SDAT were decreased compared to middle-aged controls, but increased in comparison to age-matched controls. IGF-I receptor densities were unchanged in aging and in SDAT. Tyrosine kinase activity, a signal transduction mechanism common to both receptor systems, was reduced in SDAT in comparison to middle-aged and age-matched control groups. These data are consistent with a neurotrophic role of insulin in the human brain and a disturbance of insulin signal transduction in SDAT brain and favor the hypothesis that insulin dependent functions may be of pathogenetic relevance in sporadic SDAT.

Mid-life onset of dietary restriction extends life and prolongs cognitive functioning

Fourteen-month-old C57BL/6 (NIA) mice were placed on a nutritionally complete diet providing 139.4 kcal/week. Over a 2-month period the food ration of experimental mice (AE) was reduced to 85 kcal/week, where it remained for the duration of the study. An aged control group (AC) continued with the higher calorie diet. At age 22 months, AC mice and half of the AE mice (AE22) were given a battery of behavioral tests. The remanining AE mice (AE25) were given the test battery at age 25 months. Also, a middle-aged control group (MC) was tested at age 13 months. Mid-life onset caloric restriction (CR) increased longevity and preserved strength, coordination, and spontaneous alternation behavior, and altered responses to enclosed alleys. A spatial discrimination in the Morris water maze and a spatial delayed matching-to-sample water-escape task were insensitive to age and diet. The aged mice were adversely affected by testing.

Comparison of DSIP- (delta sleep-inducing peptide) and P-DSIP-like (phosphorylated) immunoreactivity in cerebrospinal fluid of patients with senile dementia of Alzheimer type, multi-infarct syndrome, communicating hydrocephalus and Parkinson's disease

The concentrations of delta sleep-inducing peptide (DSIP)-like (DSIP-LI) and P-DSIP-like (phosphorylated, Ser7) immunoreactivity (P-DSIP-LI) were measured by specific radioimmunoassay in the cerebrospinal fluid (CSF) of patients with senile dementia of the Alzheimer type [SDAT, subdivided into early (S1), middle (S2) and late dementia (S3)], multi-infarct dementia (MD), Parkinson's disease (PD), vascular disease (VD) and communicating hydrocephalus (H), as well as in control patients (C1, C2). Mean DSIP-LI and P-DSIP-LI concentrations were found to be significantly higher in the elderly control group (C1, mean age 83 +/- 5 years) than in the middle-aged control group (C2, mean age 40 +/- 16 years). DSIP-LI and P-DSIP-LI were positively correlated with age in both control groups. Significant decreases of DSIP-LI compared with age-matched controls (C1) were observed for S2, S3, MD, PD, VD and H. In contrast, no significant differences corresponding to pathology were found for P-DSIP-LI.

Decreased glucose-induced thermogenesis after weight loss in obese subjects: a predisposing factor for relapse of obesity?

Glucose-induced thermogenesis (GIT) after a 100-g oral glucose load was measured by continuous indirect calorimetry in 32 nondiabetic and diabetic obese subjects and compared to 17 young and 13 middle aged control subjects. The obese subjects were divided into three groups: A (n = 12) normal glucose tolerance, B (n = 13) impaired glucose tolerance, and C (n = 7) diabetics, and were studied before and after a body weight loss ranging from 9.6 to 33.5 kg consecutive to a 4 to 6 months hypocaloric diet. GIT, measured over 3 h and expressed as percentage of the energy content of the load, was significantly reduced in obese groups A and C (6.2 ± 0.6, and 3.8 ± 0.7%, respectively) when compared to their age-matched control groups: 8.6 ± 0.7 (young) and 5.8 ± 0.3% (middle aged). Obese group B had a GIT of 6.1 ± 0.6% which was lower than that of the young control group but not different from the middle-aged control group. After weight loss, GIT in the obese was further reduced in groups A and B than before weight loss: ie, 3.4 ± 0.6 (p < 0.001), 3.7 ± 0.5 (p < 0.01) respectively, whereas in group C, weight loss induced no further diminution in GIT (3.8 ± 0.6%). These results support the concept of a thermogenic defect after glucose ingestion in obese individuals which is not the consequence of their excess body weight but may be one of the factors favoring the relapse of obesity after weight loss.

A-Cholesterol percentages in coronary patients with and without increased total serum cholesterol levels and in healthy controls

Summary An attempt was made to establish a serum lipid value which could serve as an indicator for atherogenic activity. A group of middle-aged coronary patients (305 males and 83 females) were compared with a control group of middle-aged members (82 males and 83 females) of communal settlements (kibbutzim) in Israel. Total serum cholesterol levels and a-cholesterol values were determined. The differences in cholesterol levels between coronary patients and healthy controls were not striking and could not be used as a parameter of atherogenic activity. The a -cholesterol percentages of the coronary patients in this study were significantly lower than those of the control group. This difference was most evident when expressed in terms of more or less than 20 % so that this figure was set as an arbitrary limit. A good majority of the coronary patients, 82 % of the males and 78 % of the females, had a -cholesterol percentages of less than 20 %. The mean value of a -cholesterol percentage in male patients was 15.8 % and in female patients 17.1 %. Over one third of the middle-aged control group in this study had values under 20 %, indicating subclinical atherogenic activity. Only 5 of 151 young and middle-aged Yemenites and young European Jews used as absolute controls, had a -cholesterol values below 20 %. Although there exists some influence of the total serum cholesterol level on the distribution of cholesterol between the lipoprotein fractions, but nevertheless in every group composed of coronary patients and healthy controls, characterized by the same limited range of total cholesterol, the percentage of coronary patients with a -cholesterol percentage under 20 % is much higher than the percentage of the controls. The low a -cholesterol percentage was characteristic of coronary patients regardless of whether their total cholesterol levels were high, low or normal and regardless of their age. The differences were particularly striking in the subgroup of patients and controls who had low total serum cholesterol levels.