Age-related Changes In Activity Research Articles

Age-Related Changes in Activities and Localizations of Cathepsins D, E, B, and L in the Rat Brain Tissues

Altered cellular levels and localizations of four distinct intracellular proteinases, cathepsins D, E, B, and L, with aging were studied in various rat brain tissues by enzymatic and immunohistochemical methods using discriminative antibodies specific for each enzyme. With regard to two aspartic proteinases, cathepsin E was barely detectable in all the brain tissues of young adult rats, including the cerebral cortex, the hippocampus, the neostriatum, and the cerebellum, whereas cathepsin D was ubiquitously found in these tissues. Two cysteine proteinases, cathepsins B and L, also existed in these tissues of young rats at the relatively high levels of activities. In aged rats, the cathepsin D levels in all of the brain tissues examined were about twice those of young rats. Cathepsin E was markedly increased in the cerebral cortex and neostriatum of aged rats, but not in the other tissues. The levels of cathepsin B were also increased significantly in the neostriatum of aged rats, but not significantly in the other tissues. In contrast, the activity levels of cathepsin L were strikingly decreased in all the brain tissues of aged rats. At the light microscopic level, the increased immunoreactivity of cathepsins D and E in the brain tissues of aged rats was eminent in both the neurons and the glial cells, By double-immunostaining technique, the cathepsin D-positive glial cells were mainly associated with reactive astrocytes, whereas the cathepsin E-positive glial cells were largely reactive microglial cells. Western blot analyses revealed that the molecular forms of cathepsins D and E increasingly expressed in the cerebral cortex of aged rats were similar to those of the respective normal mature enzymes. The increased immunoreactivity of cathepsin B in the neostriatum of aged rats was also found in both the neurons and the glial cells. Despite the marked decrease of the cathepsin L activity in various brain tissues of aged rats, the immunostaining for this enzyme was not significantly changed, indicating the occurrence of the catalytically inactive form of the enzyme in these tissues. These results suggest that the increased levels of cathepsins D, E, and B and the decrease in cathepsin L activity in brain regions of aged rats are related to both the neuronal degeneration and the reactivation of glial cells during the normal aging process of the brain.

Age-related changes in the mitogenic activity of heparin-binding growth factors in rat sera

Sera from rats of either sex and different ages were examined for their ability to stimulate DNA synthesis in BALB/c 3T3 cells. The activity levels of sera from male and female rats were almost the same, with age-related changes in activity also being quite similar. Activity was considerably higher in infant rats (1-month-old), but then, at a young age (6–7 months), decreased drastically for male rats, but not significantly for female rats. It increased again in middle-aged rats (12–13 months old) and was maintained at the same level toward old age (24–26 months old) for both sexes. In order to determine what kinds of growth factors were responsible for these changes, were carried out heparin affinity chromatography on the sera of male rats. Four peaks were obtained for all sera, with individual peaks exhibiting specific age-related changes in activity. Among them a peak which was eluted at 1.1 M NaCl had very high activity. It showed a similar age-related change to that of the whole sera, except for a significant increase at old age, and the factor(s) included in the peak was found to be derived from platelets. These results suggested that the factor(s) in the peak was responsible for maintaining serum mitogenic activity at an old age. The experiments undertaken to characterize this factor suggested that it is a novel one.

Dissociation of Object and Spatial Vision in Human Extrastriate Cortex: Age-Related Changes in Activation of Regional Cerebral Blood Flow Measured with [15 O]Water and Positron Emission Tomography

We previously reported selective activation of regional cerebral blood flow (rCBF) in occipitotemporal cortex during a face matching task (object vision) and activation in superior parietal cortex during a dot-location matching task (spatial vision) in young subjects, The purpose of the present study was to determine the effects of aging on these extrastriate visual processing systems. Eleven young (mean age 27 ± 4 years) and nine old (mean age 72 ± 7 years) male subjects were studied. Positron emission tomographic scans were performed using a Scanditronix PC1024-7B tomograph and H2(15)O to measure rCBF. To locate brain areas that were activated by the visual tasks, pixel-by-pixel difference images were computed between images from a control task and images from the face and dot-location matching tasks. Both young and old subjects showed rCBF activation during face matching primarily in occipitotemporal cortex, and activation of superior parietal cortex during dot-location matching. Statistical comparisons of these activations showed that the old subjects had more activation of occipitotemporal cortex during the spatial task and more activation of superior parietal cortex during the object task than did the young subjects. These results show less functional separation of the dorsal and ventral visual pathways in older subjects, and may reflect an age-related reduction in the processing efficiency of these visual cortical areas.

Aging Alters the Activity of 5′-Deiodinase in the Adenohypophysis, Thyroid Gland, and Liver of the Male Rat*

Aging is characterized by a decreased secretion of thyroid hormones in rats associated with unchanged plasma TSH suggestive of impairments in the hypothalamo-pituitary-thyroid axis. Since it is known that pituitary T3 is more determinant on TSH secretion than plasma T3, we measured in young (4 months) and old (26 months) male rats the concentration of T3 in the anterior pituitary gland and found that it was similar in young and old animals despite the low circulating levels of thyroid hormones. This was suggestive of age-related differences in the intrapituitary T4 to T3 conversion. We therefore determined the activity of 5'-deiodinase (5'-D, type I and type II) in the adenohypophysis and investigated possible age-related changes in this enzyme activity in peripheral tissues by its determination in the thyroid gland and liver (type I) of young and old rats. Intrapituitary 5'-D activity was increased in old compared to young rats (type I 5'-D: 4.59 +/- 0.13 vs. 2.92 +/- 0.33 pmol rT3/h x mg protein; type II: 0.54 +/- 0.5 vs. 0.21 +/- 0.03 pmol rT3/h x mg protein; P less than 0.001). In contrast, in the thyroid gland and in the liver, type I 5'-D was reduced with age (4.7 +/- 0.6 vs. 7.4 +/- 0.8 and 3.1 +/- 0.4 vs. 5.6 +/- 0.5 nmol rT3/h x mg protein, respectively; P less than 0.01). These data are illustrative of age-related changes in the activity of 5'-D, different according to the tissues in agreement with the known tissue-specific regulation of the 5'-Ds. The reduced activity of 5'-D in the thyroid and liver of old rats is indicative of an impaired thyroid hormones disposal in peripheral tissues with age. In contrast, in the adenohypophysis of old rats, the increase in the activity of 5'-D is similar to that reported in hypothyroid animals and suggests the development with age of an adaptative mechanism in the presence of low circulating thyroid hormones; this mechanism leads to unchanged intrapituitary concentration of T3 and consequently to unaltered plasma levels of TSH in old rats.

Genetics and senescence. I. Age-related changes in activity and exploration in three inbred strains of mice

Exploratory, locomotor and ambulatory activities were measured in nine independent groups of three inbred strains of mice (BALB/cBy, C578L/6J and DBA/2J), at three different ages (150 days, 400 days and 750 days). The results show that for two of the three variables, the age-related changes present different patterns as a function of strain. The genetic and/or environmental correlates of the reactivity to aging may thus depend on the behavioral trait under study.

Age- and exercise-related changes in the activities of thiol proteinases in rat skeletal muscle.

The activities of thiol proteinases and their endogenous inhibitors in musculus rectus femoriswere studied in control and exercised rats of various ages. Cathepsins B and H, both lysosomal thiolproteinases, showed different age-related changes in activity. Two forms of calcium-activatedneutral protease (CANP), μCANP and mCANP, differ from the lysosomal thiol proteinases withregard to age-related changes in activity. The activities of endogenous inhibitors of CANP, cathepsins B and H are apparently not affected by age. Among CANP, cathepsins B and H, only theactivity of CANP (the sum of μCANP and mCANP activities) in the 16-week-old rats was reducedafter training. Exercise had no effect on the activities of endogenous inhibitors in the 16-week-and98-week-old animals. The relative percentage of the activity of μCANP to the activities of μCANPplus mCANP did not change regardless of differences of age or exercise. These findings suggest thatfactors other than endogenous inhibitors may be involved in the age- and exercise-related changesin the activities of these thiol proteinases, and also that there is a close relationship between μCANP and mCANP in skeletal muscle.

Age-Related Changes in Activities of the Superoxide Dismutase Enzymes in Tissues of the Sheep and the Effect of Dietary Copper and Manganese on These Changes

Activities of the copper-zinc- and manganese-containing superoxide dismutase enzymes (CuSOD and MnSOD) were studied in tissues of the sheep to determine the dependence of these activities on sheep age, and their relationship to tissue and dietary mineral concentrations. Tissue samples were obtained from day-old through 16-week-old lambs from flocks grazing pastures normal or high in copper and manganese, and from adult sheep. In liver, lung, heart, kidney and skeletal muscle, activities of CuSOD and MnSOD in day-old and week-old lambs were only half those measured in 16-week-old and adult sheep. Activities in 4-week-old lambs were intermediate between these two groups except for heart tissue, in which activities were not increased until lambs were 16 weeks old. For all age groups, heart and skeletal muscle had low activities of CuSOD. Minimal age-related changes were observed for CuSOD activities in erythrocyte and brain tissues. The low enzyme activities evident in most tissues of day-old lambs, occurred in the presence of apparently adequate tissue copper and manganese concentrations. Concentrations of these minerals in lamb tissues were equal to or greater than those observed in older sheep and although these concentrations increased considerably with increased pasture mineral concentrations, enzyme activities were unchanged. Age-related increases in tissue CuSOD and MnSOD activities, occurring as normal developmental processes, may be important factors in diseases attributed to uncontrolled tissue peroxidation in sheep.

Age-related changes in activities of hepatic phosphofructokinase, pyruvate kinase and pyruvate dehydrogenase in liver and adipose tissue of the swiss albino mouse.

The activities of phosphofructokinase, pyruvate kinase and pyruvate dehydrogenase were examined in liver as a function of age in Swiss albino mice. The hepatic activity of phosphofructokinase and total pyruvate dehydrogenase peaked in mice between 8 and 12 weeks of age and then decreased to a value that remained stable in mature animals older than 24 weeks of age. Yet, the activity of pyruvate kinase and pyruvate dehydrogenase in the active form in liver remained unchanged in mice up to 12 weeks of age. As mice matured, a progressive increase in the activity of both pyruvate kinase and the active form of pyruvate dehydrogenase in liver was observed while phosphofructokinase was unaltered. The pyruvate dehydrogenase complex, both total activity and the proportion of the enzyme in the active form, in the epididymal fat pad of the mouse showed no consistent age trend. The observed increase in the activity of both pyruvate kinase and the active form of pyruvate dehydrogenase should provide an augmented capacity for the generation of acetyl-CoA units for de novo fatty acid synthesis in livers of mature mice.

Energy metabolism and ageing of Phormia terraenovae—I. Programmed changes of enzyme activities and substrate concentrations in carbohydrate metabolism

1. 1. The age related activity changes of glycolytic key enzymes (PFK, aldolase, GADPH an PK; and their corresponding substrates were determined in thoraxes of male blowflies Phormia terraenovae. 2. 2. All enzyme activities rise rapidly during the first days after emergence reaching a maximum near the 12th day, thereafter they decrease to a nearly constant level between the 17th and 23rd day of adult life. 3. 3. The glycolytic capacity is reduced after the second week but no defect in the glycolytic flow appears as the constant quotient between aldolase and GAPDH and the unchanged energy charge shows. 4. 4. Flight performance is not affected by enzyme activity or substrate concentration changes.

Brain transfer ribonucleic acid methyltransferases in young adult and old mice

Enzymes which methylate transfer RNAs are known to be controlled by hormones and small molecule inhibitors. We examined the ability of such enzymes prepared from different brain regions to methylate a fixed small quantity of tRNA. We also compared methylation by enzymes from different post-pubertal ages of C57BL/6J male mice (12, 18 and 30 months of age). Different brain regions exhibited different levels of tRNA methyltransferase activity, cerebellum being more active than brain stem, which was in turn more active than cortex or hypothalamus. No age-related changes in activity were found in activity from whole brain or cortex.

Influence of Age, Sex, and Dietary Salt Intake on Rat Kidney Brush Border Enzymes

The kidney brush border membrane contains several glycoprotein hydrolytic enzymes the functions of which are currently in doubt. We have assessed the importance of age, sex, and salt intake as determinants of the activity of 5 brush border enzymes. No effect of salt loading or depletion could be appreciated. Enzyme levels corrected for age were uniformly higher in males than females except for alkaline phosphatase. Age-related changes in activities were observed to follow a nonuniform pattern with the most striking alterations affecting alkaline phosphatase and maltase in female rats. Age-associated reductions in renal function do not entirely account for reduced enzyme levels.

Age-dependent α-glycerophosphate dehydrogenase activity changes in mutant and wild type Drosophila melanogaster

The age-related changes in the activity of the extramitochondrial α-glycerophosphate dehydrogenase (α-GPDH) were compared in two mutants of Drosophila melanogaster, a vestigial-winged and an α-glycerophosphate dehydrogenase deficient mutant with that of the wild type. The age-dependent patterns of activity change in both mutants were shown to be identical to that of the wild type. This is in spite of the lack of flight ability in both mutants, the reduced enzyme activity levels in the α-glycerophosphate mutant, and in the case of the vestigial flies, of reduced life-span. The results suggest that those mechanisms responsible for the observed age-related activity changes in α-GPDH are intrinsically regulated, independent of functional flight, genetic alteration of specific activity, and life-span.

Periodicity of Wheel-Running Activity in Mice in Relation to Light-Dark Cycle; I. Strain and Age Differences

Male mice of 4 strains (C57BL/6, DBA/2, C3H/He, and I20/Se) were individually run for 24 hr in home cages with an activity wheel under normal (LD) and reversed (DL) conditions of light-dark cycle. LD condition was in light from 08 : 30 to 20 : 30, and DL condition was in light from 20 : 30 to 08 : 30, alternating with 12 hr of darkness in each condition. Brightness in the light period was about 330 lux. Each strain consisted of 4 groups (3, 5, 7, and 9 weeks of age at the beginning of the experiment) of 10 mice.As shown in Figures 1 and 2, the onset of the activities of mice in LD condition, as compared with those in DL condition, synchronized with their transition from light-on to light-off. Especially, those of the mice of DBA and I20 strains synchronized markedly. Moreover, it can be observed in the mice of all strains that transition from light-off to light-on in the time of night has a drifting effect on the onset of activity.Transformed data on the total activity for 24 hr shown in Table 1 were analyzed by 3-factorial analysis of variance. Significant values of F were obtained only in the main effects of strain (F=6. 314, df=3/288), conditions of light-dark cycle (F=13. 904, df=1/288), and age (F=3. 931, df=3/288). It can be observed from Table 2 that there are very clear differences among strains of mice in the alternation of the active and inactive periods synchronized with light-dark cycle. From these results it is suggested that the activities of DBA and I20 mice synchronize with light-dark cycle of both conditions, whereas the activities of C57BL and C3H mice do not so much synchronize with those conditions. The age-related activity changes could not be observed in the present study.We conclude from these results that the activity synchronizes with a light-dark cycle, and thus periodicity of the activity is achieved by onset response to light-off and drifting response to light-on. However, further researches are needed to determine whether the 24 hr-periodicity of activity is controlled either by light-dark cycle or by a circadian rhythmic clock.

Age-Related Activity Changes in Arginine Phosphokinase in the House Fly, Musca Domestica L

The activity of ATP; L-arginine phosphotransferase (E.C.2.7.3.3.), was shown to exhibit age-dependent changes in both male and female house fly. Enzyme activity demonstrated more marked changes in the male than in the female, increasing 44-fold from emergence to a peak at 2 days of age and thereafter declining, at first sharply then gradually to a value at 14 days of age, representing a third of the activity found at the peak. Activity in the female fly also showed a peak at 2 days of age, which thereafter declined, although more gradually than was observed in the male. Activity changes expressed on a per fly or wet weight bases were nearly identical. Age-related activity changes on a milligram protein basis demonstrated similar increases; however, the percentage decrease from the 2-day peaks were less striking, although highly significant. No kinetic or physical changes in the enzyme were detected, nor could any soluble inhibitors or activators of enzyme be identified. The changes in arginine phosphokinase activity fall into a sequential pattern of enzyme changes, reflecting an apparently ordered mechanism underlying a decline in flight ability in this species.

Age-related changes in acid phosphatase activity in adult male housefly, Musca domestica. A histochemical and biochemical study

Age-related changes in the activity of acid phosphatase, a lysosomal marker enzyme, were studied in different tissues of the adult male housefly using histochemical and biochemical techniques. Acid phosphatase activity greatly increases with age. Results of this study indicate that lysosomes may be significantly involved in the deterioration of cells in the senescent flies.