Cellular defenses against damage from reactive oxygen species.
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Animals↗
Biomedical subjects
B P Yu
Publications and source records attributed to B P Yu.
Patterns of capillaries in developing cerebral and cerebellar cortices of rats.
Patterns of capillaries in cerebral and cerebellar cortices were studied in developing rats. In cerebral cortex, the ventricular zone is well vascularized throughout the developmental period. The cell dense cortical plate is poorly vascularized, with capillary branches appearing in individual layers as they emerge from the cortical plate. In cerebellar cortex, the external granular layer appears devoid of capillary branches. Capillary branching appears first in the Purkinje and granule cell layers and later in the molecular layer. These results indicate: (1) an inside-out pattern of development of capillaries in both cortices, and (2) marked differences in vascularization of the proliferative zones for cerebral and cerebellar cortical neurons.
Aging↗
How diet influences the aging process of the rat.
Aging is a time-dependent, deleterious process known to be influenced by multiple factors and processes. Recent gerontological investigations have clearly shown nutrition to be the most powerful extrinsic factor influencing the aging process. That role has been clarified by recent inquiries on such underfeeding paradigms as calorie restriction. The idea of reduced calorie intake as a potent aging modulator contrasts dramatically with the traditional view that "more is better" which springs from the consideration of nutrition only as a source of energy and nutrients required to maintain health. This review presents pertinent data on how nutrition may influence the longevity of organisms and modulate age-related diseases.
Aging↗
Dietary restriction modulates the norepinephrine content and uptake of the heart and cardiac synaptosomes.
The present study was designed to examine the effects of long-term dietary restriction on cardiac sympathetic nerves and neurotransmitter. The food intake of male, 6-week-old Fischer 344 rats was reduced to 60% of the intake of control rats fed ad libitum. The body and heart weights of rats diet restricted for 4.5 months were less than those of the ad libitum fed animals, while the heart weight to body weight ratios were higher. The norepinephrine (NE) content of hearts from restricted rats (1073 +/- 84 ng/g wet wt) was higher than controls (774 +/- 38 ng/g wet wt), although the total amount of NE per heart was unchanged. Similarly, the cardiac synaptosomal P2 fraction from restricted rats possessed a higher NE content (24.1 +/- 2.4 ng/mg protein) than the P2 fraction of ad libitum fed controls (13.7 +/- 1.3 ng/mg protein). The desmethylimipramine-sensitive norepinephrine uptake of the P2 fraction from restricted rats was significantly higher than that of control rats (9.44 +/- 1.33 vs 4.75 +/- 0.35 ng/mg protein/hr). The NE uptakes of the two groups were similar when uptake was normalized to endogenous NE levels. These results demonstrate that long-term dietary restriction affects cardiac sympathetic nerve endings and suggest that part of the beneficial action of life-long dietary restriction on the age-related decline in cardiovascular regulation may be related to changes in cardiac sympathetic nerves.
Animals↗
Need the free radical theory of aging be linked to the metabolic rate theory?
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Aging↗
Diet and the suitability of the male Fischer 344 rat as a model for aging research.
There has been concern about the suitability of the male Fischer 344 (F344) rat as a model for aging research because of the high prevalence of a single disease, severe nephropathy, at advanced ages which confounds the interpretation of an aging study. In a publication from our laboratory, Iwasaki et al. (1988) reported that replacing the casein in our standard semisynthetic diet with soy protein markedly decreases the progression of nephropathy with advancing age in ad libitum fed male F344 rats. In the present study, it is shown that replacing the casein with lactalbumin does not decrease the occurrence of severe nephropathy in ad libitum fed rats. It is also shown that dietary restriction (DR) studies can be effectively executed in the male F344 rat when soy protein is the source of dietary protein. It is further shown that when the energy intake of the rats fed soy protein-containing diets was reduced to 60% of the ad libitum intake, almost one-third of the rats died with an absence of severe morphologic lesions, that is, lesions which contribute to the death of the rat. It is concluded that the male F344 rat is an excellent model for aging research when soy protein is the source of dietary protein; no single disease process was found to be primarily responsible for death with such a diet.
Aging↗
Dietary restriction retards onset but not progression of leukemia in male F344 rats.
The objective of this study was to determine the effect of dietary restriction on the spontaneous occurrence and the progression of leukemia in male F344 rats. The analysis involved both sacrificed rats and those that died spontaneously. These rats had been either ad libitum fed (AL) or restricted to approximately 60% of the ad libitum intake (DR) from 6 weeks of age. Dietary restriction delayed spontaneous death due to this disease by delaying the occurrence of leukemia. However, dietary restriction did not retard its progression, i.e., the time between occurrence and death.
Age Factors↗
Modulation of membrane phospholipid fatty acid composition by age and food restriction.
Phospholipids from liver mitochondrial and microsomal membrane preparations were analyzed to further assess the effects of age and lifelong calorie restriction on membrane lipid composition. Results showed that the major phospholipid classes, phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol and cardiolipin did not vary significantly with age or diet. The fatty acid composition of the phospholipids was determined in PC and PE and ages of 6, 12 and 24 months. The data revealed characteristic patterns of age-related changes in ad libitum (AL) fed rats: membrane levels of long-chain polyunsaturated fatty acids, 22:4 and 22:5, increased progressively, while membrane linoleic acid (18:2) decreased steadily with age. Levels of 18:2 fell by approximately 40%, and 22:5 content almost doubled making the peroxidizability index increase with age. In addition, levels of 16:1 and 18:1 decreased significantly with age, indicating a possible change in delta 9-desaturase activity coefficient. Food restriction resulted in a significant increase in levels of essential fatty acids while attenuating levels of 22:4, 22:5, 22:6 and peroxidizability. We concluded that the membrane-stabilizing action of long-term calorie restriction relates to the selective modification of membrane long-chain polyunsaturated fatty acids during aging.
Aging↗
Is poly(A) tail length altered by aging or dietary restriction?
We examined age- and diet-related alterations in RNA poly(A) tail length using high-resolution gel electrophoresis followed by Northern hybridization. The results demonstrate conclusively that there is no age-related decrease in the size of the Poly(A) tail of RNA isolated from the male Fischer 344 rat. In contrast, our results suggest that there is actually a slight age-related increase in the length of the poly(A) tail isolated from the liver and hypothalamus of these rats. Dietary restriction did not affect either poly(A) tail length or its age-related increase. These data demonstrate conclusively that oligo(dT) probes can be used to standardize RNA hybridization experiments between animals of different ages and dietary groups. In addition, these data provide further evidence that the ratio between RNA polymerase I and RNA polymerase II activity does not change with age.
Aging↗
Antioxidant action of dietary restriction in the aging process.
Dietary restriction is widely recognized to be the most effective means of intervening in the aging process in laboratory animals. Recent studies have produced substantial evidence that indicates this nutritional manipulation can modulate many aspects of free radical metabolism, including free radical generation, lipid peroxidation, DNA damage and cytosolic defense systems. Some of our laboratory's recent work is summarized in this presentation.
Aging↗
Effect of age-related lipid peroxidation on membrane fluidity and phospholipase A2: modulation by dietary restriction.
Age-related changes in membrane property are generally accepted phenomena. In this report, using the anti-lipoperoxidative measure of dietary restriction on membranes, the age-related effects of lipid peroxidation on membrane fluidity are explored in conjunction with the membrane-associated phospholipase A2. The fluidity of mitochondrial and microsomal membranes from ad libitum fed rats shows a progressive decline with age as indicated by a substantial decrease in two parameters, l/polarization and l/anisotropy. In contrast, the membrane fluidity of dietary restricted rats shows slight changes between 6 and 24 months of age. Evidence is presented to support the possibility that age-related peroxidation of membrane lipids may play a significant role in bringing about fluidity changes in aged membranes. The findings on the increased phospholipase A2 with age is also consistent with this conclusion.
Aging↗
Protection of DNA damage by dietary restriction.
Dietary restriction is known to retard the aging processes and delay the onset of age-related neoplastic diseases. The mechanisms underlying these remarkable actions of nutritional intervention are not known in spite of recently intensified research efforts. However, the last couple of years' research on dietary restriction produced strong evidence indicating that its effective antiaging actions might be related to its ability to modulate free radical damage. In the present study, DNA damage and attenuation of the damage by dietary restriction were assessed by measuring 8-hydroxydeoxyguanosine 8-OH dG) in both nuclear DNA (nuDNA) and mitochondrial DNA (mitDNA) fractions. The data show that substantially more damage (approximately 15 times) occurred in mitDNA compared to nuDNA. More interestingly, the DNA damage was significantly attenuated in dietarily restricted rats.
Animals↗
An emerging hypothesis: synergistic induction of aging by free radicals and Maillard reactions.
Most modern theories of aging have centered around the notion that age-related deterioration is primarily due to structural and functional modifications of cellular constituents. Among them are three currently popular hypotheses--the Free Radical, Glycation, and Maillard Theories of Aging. The first proposes that age-related effects are due to free radical reactions that damage cellular constituents, while the latter propose damage induced by nonenzymatic glycation and other Maillard reactions and the consequent modification of macromolecules as the primary cause of aging. Although these hypotheses were formulated independently, recent studies suggest that free radicals, glycation, and Maillard reactions may in fact represent partially interactive elements of a single, more complex biochemical pathway. We therefore propose the Free Radical-Glycation/Maillard Reaction Theory of Aging: that age-related deterioration is produced by the sum of the damage induced by free radicals, by glycation, by Maillard reactions, and by their interactions.
Aging↗
Effect of dietary restriction and aging on polyploidy in rat liver.
Liver polyploidy levels were compared as a function of age and diet in male Fischer 344 rats between 1 and 24 months of age. Dietary restriction was imposed on one group by reducing their food intake to 60% of ad libitum food intake. Histological sections of the livers of animals at each age and diet were examined. Diploid, tetraploid and octaploid nuclei were observed, and their size and frequency established. There were no differences in the diameter or volume of these size classes as a function of age or diet. An age-related decline in the percentage of diploid nuclei, coupled with an increase in the percentage of tetraploid and octaploid nuclei was observed in both groups. The major difference between the two groups was that the adult level of liver polyploidy was attained more slowly in the animals on dietary restriction as compared to the ad libitum fed controls. Polyploid cell formation in the liver is under the control of growth hormone, thyroid hormone and thymus, all of which might be influenced by dietary restriction.
Aging↗
Food restriction retards aging of the pineal gland.
The effects of chronic (40%) food restriction from 6 weeks of age were studied in aging male Fisher 344 rats. When compared with 3-month-old, ad libitum fed rats, pineal N-acetyltransferase (NAT) activity had declined to less than 30% and pineal and serum levels of melatonin to 40% after 28 months when feeding had been ad libitum. Food restriction significantly retarded this development (P less than 0.05) giving NAT and melatonin levels which were twice as high as in the ad libitum fed group. Nighttime levels of pineal serotonin (5-HT) were similar in food-restricted and ad libitum fed old rats but were nearly twice as high (P less than 0.05) as in young rats. There was also a tendency for increased production of 5-hydroxyindoleacetic acid (5-HIAA) in the pineal gland with higher levels of 5-HT. It is concluded that aging in the rat (Fisher 344) is accompanied by a reduction of pineal NAT activity, thereby reducing the production of melatonin and causing a buildup of 5-HT in the pineal gland. It is furthermore proposed that food restriction, which markedly increases the life span and reduces age-related physiological deterioration and diseases in many animals, may mediate some of its effects through a sustained pineal activity in old age.
Aging↗
Development of cholinesterase histochemical staining in cerebellar cortex: transient expression of "nonspecific" cholinesterase in Purkinje cells of the nodulus and uvula.
Patterns of "nonspecific" cholinesterase (ChE) and acetylcholinesterase (AChE) activity were studied in developing rat cerebellar cortex by enzyme histochemistry and light and electron microscopy. Three types of ChE histochemical reaction product were observed in cerebellar cortex: (i) ChE is found in capillary endothelium throughout the cerebellum. Capillary ChE staining is present by the time of birth and continues into adulthood. (ii) ChE is found in radial glial fibers and their parent cell bodies, the Golgi epithelial cells. Radial glial fiber staining is mot intense during the first 3 weeks of postnatal life. (iii) ChE is found in Purkinje cells of the nodulus and ventral uvula. No ChE staining of Purkinje cells was seen in other parts of the cerebellum. ChE staining of Purkinje cells appears to be transient, first appearing at Postnatal Day 2 (P2), reaching peak intensity at P7-9, and decreasing to adult levels by P16. AChE activity displays a pattern markedly different from ChE, with staining in deep cerebellar nuclei, in putative mossy fiber terminals, and in Golgi neurons of cerebellar cortex. No evidence was found for transient AChE staining in Purkinje cells in any part of the cerebellum. The function of transiently expressed ChE activity in developing Purkinje neurons is unknown, but may be related to reorganization of cerebellar cortical circuitry associated with growth of mossy fiber afferents.
Acetylcholinesterase↗
Influence of diet on fatal neoplastic disease in male Fischer 344 rats.
The influence of dietary manipulations on fatal neoplasms in male Fischer 344 rats was assessed. Particular attention was paid to leukemia and pituitary adenoma because they are the most common potentially fatal neoplasms that occur in this rat strain. The only dietary manipulation which depressed the mortality rates due to neoplastic disease was that involving a reduction in energy intake. Reduction of mineral or protein or fat intake without a reduction of energy had, at most, marginal effects on fatal neoplastic disease.
Adenoma↗
Retardation of the aging processes in rats by food restriction.
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Aging↗