Showing papers in "Age in 1980"

Free radical theory of aging: Beneficial effect of antioxidants on the life span of male NZB mice; role of free radical reactions in the deterioration of the immune system with age and in the pathogenesis of systemic lupus erythematosus

Abstract: Autoimmune manifestations increase with age. Tolerance to self-antigens appears to be actively maintained mainly by T-suppressor cells derived from radio-sensitive precursors. Since endogenous free radical reactions seem to increase with age the associated increase in autoimmunity could be due, at least in part, to a disproportionate decrease in suppressor cell function, as compared to the other cells of the immune system. This possibility was evaluated using New Zealand black (NZB) mice; this strain loses T-cell suppressor function early in life and develops autoimmune manifestations which mimic those seen in old mice of normal strains. Addition of 0.25%w (percent by weight) α-tocopheral acetate, 0.25%w Santoquin (a quinoline derivative), or 1.0%w NaH2PO2 to the diet of NZB male mice, starting shortly after weaning, increased the average life span by 7.1, 32.1 and 1.2 percent, respectively, by comparison with the control life span of 16.8 months. These data support the above-suggested explanation for the rise in autoimmunity with age. The NZB mouse serves as a model for systemic lupus erythematosus (SLE). The present study led to the suggestion that the basic defect in SLE is an abnormality(s) which enhances the tendency for nuclear antigens to be formed from nuclear components by a free radical pathway. The nuclear antigens in turn give rise to immune complex disease. Thus the beneficial effect of antioxidants in the present study can be attributed to a decrease in the rate of: 1) formation of nuclear antigens, 2) free radical damage initiated by aggregating neutrophils, and 3) free radical reaction-induced loss of T-suppressor cell function with age owing to a reduction in damage from both “normal” endogenous free radicals and those of neutrophil origin.

Free radical theory of aging: origin of life, evolution, and aging

Abstract: The free radical theory of aging postulates that damage caused by free radical reactions contributes to aging and age-associated diseases. Dietary changes designed to minimize free radical reactions have been shown to: 1) increase the life span of mice, rats, fruit flies and nematodes, 2) inhibit development of some forms of cancer, 3) enhance humoral and cell-mediated immune response, and 4) slow development of the autoimmune disorders, amyloidosis and that of NZB mice. In addition, free radical reactions may play a significant role in the degradation of the cardiovascular and central nervous systems with age. Further support for the possible involvement of free radical reactions in aging comes from studies on the origin and evolution of life briefly summarized in this paper.

Glutathione levels in hepatic and extrahepatic tissues of mice as a function of age

Abstract: Glutathione is the most abundant thiol-containing component in living cells and is believed to play an important role as an antioxidant. We have examined the levels of reduced, oxidized, and total glutathione in liver, blood, kidneys, and intestinal mucosa of mice as a function of age. Reduced glutathione levels decreased in kidneys, Intestinal mucosa, and blood while total glutathione levels decreased in all tissue with advanced age. Highest concentrations of reduced glutathione per μg protein were present in liver and intestinal mucosa. Our results support the hypothesis that a decrease in reduced glutathione may contribute to changes associated with aging as well as to the increased susceptibility to disease processes which occur with advanced age.

Reflections of biological changes in the psychological performance of the aged

Abstract: It is demonstrated in the course of a longitudinal study of aged twins that individuals who developed symptoms resulting in a psychiatric diagnosis of dementia had significantly lower scores on three tests of cognitive function as early as 20 years before the diagnosis was made. Prospective longitudinal studies will be required to confirm the utility of psychometric tests as predictors of subsequent dementia; nonetheless, the present results suggest that it may be possible to identify behavioral phenotypes of dementia-prone aged persons.

Age differences in short-term memory of test-sophisticated rhesus monkeys

Abstract: Aged rhesus monkeys trained for 3 months on a delayed-response task are impaired relative to young, adult monkeys similarly trained. The delayed-response performance of eight aged (18 + years) and five young (5–8 years) adult monkeys after extensive training (> 1 yr) on the task was examined. Recall of the spatial position of a visual stimulus was measured following retention intervals of various durations using a delay titration method. It was found that increased experience on the task improved performance in both age groups. However, aged monkeys remained reliably and significantly impaired under conditions requiring short-term memory. These findings further confirm the utility of nonhuman primate models of age-related cognitive deficits in humans.

Altered drug metabolism in hepatic and extrahepatic tissues in mice as a function of age

Abstract: An increase in the susceptibility to drugs is known to occur with advanced age. Several possible explanations for this phenomenon exist, but the exact cause has not been determined. Aryl hydrocarbon hydroxylase (AHH), 7-ethoxycoumarin O-deethylase (ECD) and aniline hydroxylase activities of hepatic and extrahepatic tissues as well as hepatic cytochrome P-450 content of female Swiss Webster mice at 1, 3, 6, 9, 12, 15 and 18 months of age were examined. AHH activity in liver and intestine reached a maximum at 6 mo. of age and began to decline thereafter. No change in pulmonary AHH activity was observed with age. ECD activity in liver as well as lungs was maximal at 6 mo. of age and decreased thereafter. Hepatic aniline hydroxylase activity exhibited over a 700% increase between one to six mo. of age, and declined by approximately 52% by 15 mo. of age as compared to peak activity. Hepatic cytochrome P-450 content was highest at 3 mo. of age and significantly decreased by 12 mo. The results demonstrate that decreases in microsomal mixed function monooxygenase activities do occur with advanced age and may contribute to a decreased rate of metabolism and increased susceptibility to drugs and other foreign chemicals with age.

Sexual behavior and some of its physiological consequences in persistently estrous aged female rats

Abstract: Sexual behavior and some of its consequences were assessed in female rats which, with advancing age, had come to exhibit persistent vaginal estrus (PVE). Sexual receptivity, defined by the animal’s readiness to exhibit lordosis when mounted, was comparable across all ages evaluated. However, sexual proceptivity, defined by measures indicative of the female’s seeking mating opportunities, was determined to be much suppressed in 18 to 20 month old PVE females compared to either younger cyclic females or 12 to 15 month old PVE females. Mating disrupted the PVE pattern. The length of time animals remained out of estrus was positively correlated with the number of intromissions achieved by the male. However, pregnancy was not observed in any of the PVE females and examination of their ovaries and the responses of their uteri to traumatization provided no evidence of progestational responses in these animals. The behavioral data indicate that with continued exposure to the hormonal conditions of PVE there is a suppression of systems mediating the proceptive components of sexual behavior in female rats. It is suggested that changes in the concentrations of pituitary and/or ovarian hormones reported to occur as PVE rats continue to age may account for these changes in behavior.

Dietary fat saturation and cholesterol turnover in aging rats

Abstract: Aging has been shown to result in changes in cholesterol metabolism resulting in Increased concentration in the serum. The turnover of cholesterol is regulated, in part, by its retention in peripheral tissues. Conversion of cholesterol to acidic form in peripheral tissues has been reported. This report examines the retention of 4-14C-cholesterol in the livers and carcasses of male and female rats fed diets containing fats of polyunsaturated to saturated ratio 0.2 (BT diet) or 1 (M diet)until they were 9, 12, 15, 18, or 21 months of age. The tracer cholesterol was given 28 days prior to necropsy and tissues were analyzed for neutral and acidic 14C, cholesterol and cholanoic acids. Age beyond 1 year resulted in an increase of retention of 14C-cholesterol in the carcass while concentration remained constant, indicating slower turnover of cholesterol. There was no consistent diet effect, but males had greater retention than females. Retention of 14C which had been transformed to an acidic form followed an age pattern similar to that of cholesterol, except M diet caused greater retention of acidic 14C after 15 months than did BT diet. Carcasses contained about 1 mg cholesterol per gm and 30–100 μg/gm of cholanoic acids regardless of weight, age, sex or diet. Changes in sterol turnover and peripheral tissue catabolism of cholesterol are concluded to be affected by age and to contribute to the mechanism of increase in serum cholesterol with advancing age.

Cyclic nucleotide exudation by nematodes and the effects on nematode growth, development and longevity

Abstract: The levels of the cyclic nucleotides, cAMP and cGMP, in the medium of aging mass cultures of Panagrellus redivivus were determined, respectively, by a protein binding assay and a radio-immunoassay. The amount of cGMP increased as the mass cultures aged while the amount of cAMP remained stable. Since premature death and an inhibition of development have been observed in aging mass cultures, investigators have speculated that a build-up of excretory products in the medium might be toxic to the nematodes and cause abnormal development. To examine this possibility, small cultures containing fixed numbers of the nematode Caenorhabditis elegans were exposed to levels of cGMP analagous to the levels found in aging mass cultures of P. redivivus. Significant increases in growth and longevity occurred with no effect on fecundity, timing or the duration of the reproductive period. It appears then that cGMP is not responsible for the toxic effects observed in mass culture and, in fact, cGMP apparently enhances nematode longevity at concentrations which do not alter normal development.

Galactokinase activity and red blood cell age

Abstract: Human erythrocyte galactokinase has been studied during red cell aging. The decay rate of enzyme activity is slower than glucose-6-phosphate dehydrogenase which is used as red cell age marker. The Michaelis constants for galactose and ATPMg2− of galactokinase of young cells are similar to the Km’s of the enzyme of total cells, while the Km increases in old cells. The behaviour of galactokinase during cell aging is similar to that of other erythrocyte enzymes.

The effect of age on aldolase in the livers of rats

Abstract: The specific activities of aldolase of cytosols isolated from the livers of 30–31-month-old rats were statistically significantly lower (P <.01) than those isolated from young animals. Although the present study provides consistent evidence for the presence of inactive aldolase in the cytosols isolated from old rats in both studies of immunoprecipitation (13–22% inactive enzyme molecules) and purification of the enzyme (15%), the age-associated changes were smaller than those previously reported for mouse. Since it is possible that there are intrinsic differences between rats and mice which may mask similar age differences, a number of variables which may influence or provide information regarding the synthesis of aldolase were also investigated in rats and mice. The data clearly indicated that in addition to age, rats and mice respond in a qualitative but not quantitative manner to dietary manipulation. For example, an increase in aldolase activity occurs in both rats and mice fed either a high fructose-no fat (HF-NF) or a low protein-high carbohydrate diet. However, the response was markedly greater in mice than in rats.

Age-associated changes in the electrophoretic pattern of the high molecular weight non-histone proteins from mouse liver, hepatoma and spleen chromatin

Abstract: The water-soluble fractions of non-histone chromatin (NHC) proteins were isolated from 0.35M NaCl extracts of liver and spleen chromatin of young and old CBA mice and hepatomas of old mice. SDS-disc electrophoretic patterns of proteins with higher molecular weight were compared. Tissue specificity and age changes of the patterns have been found; however, in spleen chromatin the differences of NHC proteins associated with aging were insignificant. Age-associated changes of NHC proteins in liver (increase of number of minor protein fractions) are not found in chromatin from hepatomas which indicates that the changes of the pattern of NHC proteins in aged liver cells are probably reversible.

Age related accumulation of intranuclear membranous inclusions in female mice.

Abstract: The nuclei of cells from the supraoptic nucleus (SON) of virgin female C57BL/lcrfat mice, ranging from eight to thirty-two months of age, were studied by electron microscopy. A quantitative study has shown that the frequency of membranous and fibrillar inclusions within the cell nuclei increase with age, but the membranous inclusions decline at extreme age, (32 months). Inclusions of either type were rarely encountered in young or old male mice.

Phenytoin-induced serum copper and ceruloplasmin in C57BL/6J mice of different ages

Abstract: Phenytoin (diphenyihydantoln) given orally to male C57BL/6J mice increased the serum copper and ceruloplasmin concentrations Young adult mice showed a maximum increase of 107% in ceruloplasmin accompanied by a 102% increase in copper The ceruloplasmin of middle-aged mice increased 53% and the copper 64% For old mice the corresponding increases were 20 and 21% Phenytoin was toxic to old mice, and middle-aged mice experienced a higher rate of death when given phenytoin for 167 days After 14 days, phenytoin decreased liver copper by 18% without significantly changing copper levels in kidney, brain or heart Feeding phenytoin for 167 days lowered liver copper by 14%, increased kidney by 9% and brain by 25% Copper in the heart remained unchanged We proposed that the status of copper in the brain may be important in epilepsy

Alloxan-induced diabetes in young vs old spontaneously hypertensive rats (SHR)

Abstract: Young and old, male and female, spontaneously hypertensive rats (SHR), were subjected to severe alloxan diabetes. Young and old diabetic SHR became emaciated with reduced heart weights and blood pressure. SHR developed progressively worsening hyperlipidemia and hyperglycemia with age. Diabetic old SHR were unable to mobilize glucose or lipid, i.e., trigycerides, free fatty acids, or total cholesterol, as effectively as their younger counterparts. BUN levels were lower in older SHR and even lower in diabetic old SHR. Older SHR secreted supranormal quantities of corticosterone; young SHR secreted subnormal quantities. Old, diabetic SHR developed extensive myocardial fibrosis, cerebral edema, gonadal atrophy and extensive intimal hyalin fibrosis of the gonadal arteries, and calcification of the medium-sized testicular arteries. The genetic programming of hypertension in SHR may affect the variety of degenerative changes which develop in young vs old SHR during severe diabetes.

Cell proliferation and the aging brain

Abstract: Human brain cells were cultured from post-mortem tissue obtained from normal adults ranging in age from 15 to 73 years Over 50% of the explant cultures set up were successful, success rates being significantly greater for gray than white matter Tissue samples obtained less than 20 hours post-mortem had a slightly but not significantly higher rate of successful cultures than those obtained after a longer delay A statistically significant age-related decrease in the frequency of successful cultures was found for white matter only, the rate for gray matter remaining constant across the three age groups (less than 40 years, 41–64 years and over 65 years of age) Research reports in the literature have concentrated almost exclusively on age-associated changes in gray matter In light of the present findings, it is recommended, therefore, that future neuroanatomical and histopathological investigations include the white matter as well