The effect of the antibiotics gentamycin and chloramphenicol on lens opacity was studied in an organ culture system. Opacity was monitored by split laser beam. Both antibiotics enhanced the onset of opacity in the cultured lenses under a variety of conditions. For instance, treatment with 5.0 mg/ml gentamycin for 60 min caused initial opacity after 4.8 +/- 1.3 days as opposed to untreated lenses at which initial opacity appeared after 18.1 +/- 2.99 days. Exposure to 20 mg/ml chloramphenicol for 60 min caused initial opacity after 4.6 +/- 1.51 days. Continuous exposure to penicillin and streptomycin (0.1 mg/ml each) did not enhance the onset of opacity.

Age Factors↗

PubMed1989

Effect of exercise on the kidney of aging mice.

Quantitative light microscopic and ultrastructural kidney changes were studied in young and old mice subjected to moderate exercise. While there was little or no change in the glomeruli of the young animals, the older age-group showed progressive and statistically significant mesangial sclerosis with obliteration of capillary lumina. Electron microscopy also showed electron dense deposits in both the mesangium and subendothelium. Kidney weight in the young mice subjected to exercise was decreased when compared with the controls, while old animals showed a higher kidney weight after 6 weeks of running exercise. Our results of progressive kidney changes in old exercising animals, together with previous studies on myocardial and skeletal muscle showing parallel changes, stress the need for careful clinical studies on the possible damage of these organs in older people who engage in jogging and heavy exercise.

Aging↗

PubMed1988

Oxygen free radical production by mouse peritoneal macrophages as a function of age.

The ability of thioglycollate-elicited peritoneal macrophages (PM) from young and senescent C57BL/6J mice to produce oxygen free radicals was assessed by luminol-dependent chemiluminescence (CL) after introduction of phagocytic stimuli. A significant age-dependent variation in the CL response was detected. A 2-fold increase in the oxygen reactive species was produced by senescent PM in response to latex and zymosan stimulation; but, the capacity to ingest latex and zymosan A particles did not vary significantly between PM from young and senescent mice. Peritoneal macrophages from both age groups responded much more vigorously to opsonized zymosan. The response of the PM from young mice was, however, 2.8-fold higher than that of old ones. There was no age-related difference in oxygen free radical production after stimulation with phorbol myristate acetate (PMA). Also, no age-dependent differences were found in the relative contribution of the various oxygen reactive species O2.-, OH., 1O2 and H2O2) to the overall oxidative burst, with latex zymosan A or PMA.

Aging↗

PubMed1988

Altered enzyme function and premature sequestration of erythrocytes in aged individuals.

Experimentation performed to determine the parameters of the life-span of the erythrocyte in hosts of various ages have determined that, in aged individuals, the rate of turnover of cells is considerably increased over that observed in young individuals. These observations are based on studies in humans, rats, mice, and rabbits in which either in situ 59Fe labelling or age-density gradient separation were used. The mechanisms for the recognition of the effete red cell in the aged host and the nature of the membrane alterations that bring about the premature sequestration are not fully understood. However, it has been consistently observed that the red cells of aged individuals have higher levels of IgG bound to their membranes than do young cells, with the most dense cells having the highest levels of immunoglobulin. Studies of most enzymes, particularly those involved in protection against oxidative damage have shown reduced activity as a function of both cell and donor age. Evidence of enzyme damage has been observed even in the youngest circulating red blood cells of old individuals. This fact leads us to hypothesize that the erythrocyte of the aged individual as it differentiates and is released from the bone marrow is less functional and partially damaged. The erythrocytes of both old and young individuals age in the circulation, accumulating subtle alterations that are recognized by the immune and/or reticuloendothelial systems and lead to sequestration. The cells of the elderly individual accumulate a greater degree of damage due to their initially reduced capacity to protect themselves from environmental stress. These alterations eventually bring them to their early sequestration.

Aging↗

PubMed1987

Defective superoxide-dismutase molecules accumulate with age in human lenses.

The specific activity of superoxide dismutase (SOD) in human transparent lenses declines as a function of age. Immunotitration using monospecific antibodies showed that, with increasing age, lenses exhibit an accumulation of catalytically inactive, but antigenically reactive, enzyme molecules. Antiserum produced against denatured enzyme removed the inactive molecules from the lens homogenates without affecting the enzyme activity. These aberrant molecules are at least partially denatured and are totally devoid of catalytic activity.

Adolescent↗

PubMed1987

Effects of aging and physical training on the neuromuscular junction of the mouse.

The effects of age and physical exercise on synaptic function were studied in the neuromuscular junctions of three skeletal muscles of C57BL/6J mice subjected to a regimen of 10 weeks of physical training (30 min/day, 3.5 m/min). Synaptic function was found to be considerably reduced in old age, as revealed by the activity of the cholinergic enzymes choline acetyltransferase (CAT) and acetylcholinesterase (AChE). However, the number of acetylcholine receptors, as judged by specific bungarotoxin binding, was found to be unchanged with either age or exercise. The regimen of training employed did not further reduce CAT and AChE activities beyond the age-dependent changes observed. It is quite possible though that the age-associated decrement in enzyme activities can account for the reduced adaptability of the muscle to exercise in old age.

Acetylcholinesterase↗

PubMed1987

Effects of long-term running stress on the ultrastructure of the aging mouse heart.

Apical regions of the left ventricular myocardium of female C57BL/6J mice, aged between 6 and 27 months, that had been subjected to endurance running for 2, 10 or 15 months, were examined by light and electron microscopy. Focal degenerative changes were found in myocytes of these experimental mice, including loss of myofibrils, erosion of myocytes and changes in nuclei, lipofuscin content and mitochondria. The interstitial connective tissue showed an increase in collagen in aged myocardia. Endurance-trained runners frequently showed signs of platelet aggregation or microthrombi in small capillaries associated with myocytes. These were most common in endurance-trained middle-aged and very elderly mice, but were not found in sedentary age-matched controls. Our experiments indicate that running stress may be damaging to cardiac tissue in aged animals. Our findings may be of significance in helping the understanding of the development and the etiology of stress-induced cardiovascular damage in the elderly.

Aging↗

PubMed1987

Giant mitochondria in the myocardium of aging and endurance-trained mice.

During the course of an ultrastructural study on the apex region of the left ventricular myocardium of experimental female C57BL/6J mice, aged between 6 and 27 months, and that had been subjected to long-term daily enforced endurance running schedules, we encountered some instances of unusual giant mitochondria. These mitochondria showed degenerative changes including the disruption, disorganization and loss of cristae and the development of a very electron-lucent matrix. In many instances, these giant mitochondria showed dense inclusions within the matrix. The giant mitochondria appear to have developed as a result of fusion between adjacent hypertrophic mitochondria followed by a sequence of progressive degenerative changes. These giant mitochondria were most common in the myocardium of mice that had followed endurance training schedules for 10 or 15 months and were not encountered in age-matched nonrunning control mice.

Aging↗

PubMed1987

Effect of aging and exercise on the kidney. Anatomical and morphological studies.

The effect of short-term endurance exercise on the kidneys of C57BL/6J mice of various ages was studied. While as a function of age there was a slight increase in the ratio of kidney weight to body weight, after 6 weeks of training there was a significant hypertrophy of kidneys of old mice compared to young ones. In addition to these gross anatomical studies, light- and electron-microscopic studies were performed. Using light microscopy, semiquantitative morphological assessment of kidney damage revealed that in young animals about 66% of total glomeruli were characterized as normal. 32% of the glomeruli were singled out as slightly damaged but still functioning. These values remained basically the same for kidneys of young animals trained for 6 weeks. In old mice, on the other hand, only 37% of total glomeruli were characterized as normal morphologically, and over 60% showed various degrees of kidney sclerosis. Exercise for 6 weeks reduced the proportion of normal-appearing glomeruli to 6.25%, while the damaged glomeruli of all types increased to over 90%. Electron-microscopic pictures revealed an increased amount of mesangial damage and severe obliteration of capillary lumens in aging animals. These changes were magnified in old running mice. The results may indicate that while kidneys of young animals were not affected by 6 weeks of exercise, kidneys of old animals were adversely affected by this type of exercise regimen.

Aging↗

PubMed1987

Age-related trend for osteopenia in femurs of female C57BL/6 mice.

Age-related changes in femoral cortical bone were quantified in female C57BL/6 mice. Variables included in this study were cortical thickness; number of osteocytes and periosteal preosteoblasts; bone DNA, protein, calcium, and phosphorus content; and uptake of 3H-thymidine, 3H-proline, and 45CaCl2. Also, the activity of bone alkaline and acid phosphatase was measured as well as the hydroxyproline content of the tissue. Femurs of old mice 28 months old, compared to those of young mice 7 months old, showed significant decreases in cortical thickness, number of bone cells, bone mineral content, and enzyme activity. The latter were accompanied by a marked reduction in ability to incorporate radiolabeled precursors of DNA and collagen synthesis as well as of the mineralization process. Hence, aging female C57BL/6 mice reveal structural and biochemical features indicative of developing osteopenia.

Aging↗

PubMed1986

G6PD molecules devoid of catalytic activity are present in the nucleus of the rat lens.

The specific activity of glucoso-6-phosphate dehydrogenase (G6PD) in the rat lens declines as a function of animal age. G6PD activity could be found only in the cortex of the lens. Previous work showed that antibodies against the 'native' form of G6PD could not recognize any cross-reacting material (CRM) in the lens. It was speculated that this could be due either to disappearance of G6PD from the nucleus by degradation or by alterations of the molecules which resulted in the loss of their antigenic determinants. In order to investigate this question, an antibody was prepared against denatured G6PD. This antibody did not interact with 'native' (active) forms of the enzyme; it was shown, however, to recognize antigenically cross-reactive but catalytically inactive intact G6PD molecules in the nucleus of the lens. This finding suggests that altered enzyme molecules are at least partially denatured and accumulate in the lens without being further cleaved proteolytically.

Aging↗