摘要:

Yellow fluorescent lipofuscin deposited in rat tissues was extracted in an aqueous solution. Yellow fluorescence with fluorescence maxima at 400/615-620 nm was detected in the aqueous extracts of brain and kidney of older rats. Purification and characterization of the yellow fluorescent components extracted from rat kidney were attempted. Centrifugal fractionation of the extract revealed that the fluorescence was detected in the 105,000 g supernatant, and not in nuclei, mitochondria, lysosomes, mi crosomes and cell debris. Gel filtration of the supernatant through Sephadex columns gave at least 5 yellow fluorescent components with different molecular weights. The higher-molecular-weight components were converted into the smaller ones on treatment with alkali or ethanol, but may not be on protease treatment. These components were adherent to polymers composed of sugars. They were soluble in water and not in an organic solvent. While the yellow fluorophores were stable on borohydride treatment, they were destroyed on heavy metal ion treatment. The characteristics of the yellow fluorophores were different from those of bluish lipofuscin-like fluorophores generated by lipid peroxidation.

ISSN:0304-324X    

DOI:10.1159/000213720

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

One of the autofiuorescent compounds that accumulates within the lipofuscin granules of the human retinal pigment epithelium (RPE) has now been identified as a quaternary nitrogen-containing cationic amphiphile (the bis-retinoid pyridinium salt, A2-E). Experimental evidence suggests that it may be responsible for lipofuscinogenesis in the RPE through its ability to inhibit lysosomal proteolysis. Furthermore, it may be involved in the events that trigger the changes leading to age-related macular degeneration (AMD), the leading cause of untreatable blindness in the elderly. It is suggested that if similar weakly basic nitrogenous compounds or cationic amphiphiles arise in reactions between amines and aldehydes in other tissues, a “self-assembling lysosomotropic amine” mechanism may provide an alternative explanation for lipofuscinogenesis those cell types as w

ISSN:0304-324X    

DOI:10.1159/000213722

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

A comparision of the response of different cell types (thymus, spleen, liver, tumor) to the development of oxidative stress was investigated on an experimental model of tumor growth in vivo. Only spleen cells exhibited the yellow-red fluorescent pigment with high resistance to oxidative stress (as is typical for age-related lipofuscin pigment). Under oxidative stress, the cytoplasm in normal cells showed a tendency foward increased levels of fluorescent products of protein or lipid peroxidation, which was opposite from the response of tumor cells. In the present paper a novel hypothesis of lipofuscinogenesis is developed where oxidative stress is considered to be a trigger for switching on some adaptive cell pathways whose activity is associated with the induction of specific groups of cellular fluorophores.

ISSN:0304-324X    

DOI:10.1159/000213723

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

When mouse peritoneal macrophages were cultured with oxidized human low density lipoprotein (ox-LDL) storage of ceroid-like pigments was observed within the cells by light and fluorescent microscopy, and fluorescence spectrophotometry. The fluorescent products exhibit the characteristics of Schiff base structures, having a fluorescence maximum of 430 nm and an excitation maximum of 355 nm, which has been generally accepted with fluorescent lipid peroxidation products. Similar fluorescent products were isolated from the atherosclerotic lesions of the aged human artery. Ox-LDL was also intraperitoneally injected into guinea pigs to study an early stage of ceroid accumulation in macrophages. An early event in guinea pigs was the appearance of neutrophils. The findings from the model systems suggest that the ox-LDL in the artery wall is probable chemotactic for neutrophils as well as monocytes. We propose the hypothesis that the production of superoxide by neutrophils causes further lipid peroxidation of native LDL and then produces large amounts of oxidatively modified LDL which is the souse of ceroid pigment accumulated within the foam cells in human atherosclerotic lesions.

ISSN:0304-324X    

DOI:10.1159/000213724

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Necropsy samples of atherosclerotic lesions of different histological stages have been analysed. Ceroid was present in all the lesions, within lipid-laden macrophage foam cells and extracellularly in the atheromatous core of advanced lesions. Mean levels of 7β-hydroxycholesterol, 26-hydroxycholesterol and hydroxyoctadecadienoic acids were all significantly greater in lesions than in normal intima. Levels of hydroxycholesterols were very low or undetectable in normal intima. Fatty streaks showed the highest ratio of 7β-hydroxycholesterol to cholesterol, and the lowest ratio of linoleate to oleate, suggesting that this type of lesion experiences the greatest free radical activity. Levels of 26-hydroxycholesterol, a product of the cytochrome P-450 enzyme sterol 26-hydroxylase, and the ratio of 26-hydroxycholesterol to cholesterol were significantly higher in advanced lesions than in intermediate lesions or fatty streaks. The ratio of α-tocopherol to cholesterol levels varied widely in normal intima but was consistently low in lesions, especially those rich in macrophage foam cells, suggesting that oxidative activity in the lesion may lead to significant oxidation of the lesion constituents only after α-tocopherol has been depleted. Macrophage death was a characteristic feature of advanced lesions, with apoptotic bodies present, and occasionally, intact apoptotic cells were seen in lesions. These striking correlations between macrophages, lipid oxidation, α-tocopherol depletion, ceroid accumulation, and macrophage death in advanced lesions, strongly support a role for oxidative damage in atherosclerosis, and lend credence to the idea that α-tocopherol dietary supplementation may slow the progression of atherosclerosis in h

ISSN:0304-324X    

DOI:10.1159/000213725

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Baret and Lints [Gerontology 1993;39:252–259] have questioned the interpretation of artificial selection experiments for increased longevity in Drosophila. They suggest that such experiments cannot demonstrate the genetic determination of longevity, because line differences in mean longevity are confounded with erratic temporal variations in life span. Using 15,000 flies from selected and control lines developed by Luckinbill and Clare [Heredity 1985;55:9–19], we show here that when lines are tested simultaneously in a carefully controlled environment, they exhibit markedly different average life spans: selected males live 20 days longer than controls, and selected females live 10 days longer. These and other observations leave no doubt about the existence of heritable variation influencing longevity in Drosophila<

ISSN:0304-324X    

DOI:10.1159/000213664

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

An important tool in the genetic analysis of longevity and aging in Drosophila melanogaster is the use of strains selected directly for late-age reproduction and indirectly for extended longevity. Following some initial failures to select for extended longevity, there are now a number of laboratories which have successfully selected for long life, using the techniques of late-age reproduction as well as selection for stress resistance. Baret and Lints [Gerontology 1993;39:252–259] have recently cast doubt on the reality of a number of these selected strains, including our own, suggesting that the difference in longevity between the long-lived and normal-lived strains disappears when the data are examined as a function of the number of days after the beginning of the selection experiment instead of as a function of the number of generations. With regard to our selected lines, they based their analysis on a subset of the published data dealing with these strains, and which covered 21 generations, or 40 months, of selection. We now present data for over 70 generations, or 155 months, of selection and maintenance. The Baret-Lints hypothesis makes two strong predictions, namely that (1) the longevity difference between the several strains should disappear when the data are replotted according to their fashion, and (2) there should be no other significant biological difference between the strains. Our data falsifies both of these predictions. The Baret-Lints hypothesis is flawed and should be disregarded. We also show that (1) the variations about the mean for six different genetically isolated strains of different longevities may be attributed to temporal alterations in the laboratory environment and (2) these variations do not obscure the genetic determinism of longevit

ISSN:0304-324X    

DOI:10.1159/000213665

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The effect of aging on plasma erythropoietin (EPO) levels after acute hemorrhage was investigated in ovariectomized (Ovx) rats. Old (22 months), middle (mid)-aged (14 months) and adult (5-6 months) Ovx rats were studied. Rats were anesthetized with ether and bled by heart puncture (5 ml/kg). They were bled again after 1 h. The hematocrit and concentration of plasma EPO were determined for both bleedings. The prehemorrhage level of hematocrit was not altered by aging. The hematocrit level after hemorrhage was greater in old than in mid-aged (p < 0.05) and adult (p < 0.01) rats. The basal level of plasma EPO in old rats was higher than that in the adult rats (p < 0.05), but not in the mid-aged rats. The concentration of plasma EPO in response to hemorrhage was increased in all rats (p < 0.01). The hemorrhage-induced increase in plasma EPO was significantly greater in adult rats than in both mid-aged and old rats (p < 0.05). Our findings indicate that the basal level of plasma EPO is increased, but the hemorrhage-induced EPO secretion is diminished in ovariectomized rats during aging. These data then suggest that the tolerance to hemorrhage and the secretory function of EPO are changed by age.

ISSN:0304-324X    

DOI:10.1159/000213666

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

While results with inhibitors of thiol proteases have led to the suggestion that the progressive increase with age of lipofuscin in post-mitotic and some stable cells may be due to an age-related decline in the activity of these enzymes (Ivy et al., 1989), no direct evidence has been yet presented to support this hypothesis. In this study Wistar female rats were killed at age of 5, 14, and 24 months and the amounts of lipofuscin were histologically quantitated in neurons of the left cerebral parietal cortex and in cardiac myocytes of left ventricle. The sites of cathepsin B activity histochemically detected were quantitated in sections from left cerebral parietal cortex and left ventricle, and the activity of this enzyme was also measured biochemically in brain and heart homogenates. In line with previous findings, the amounts of lipofuscin in neurons and cardiac myocytes increased linearly during development and aging (from 5 to 14 and from 14 to 24 mo.). The sites of cathepsin B activity histochemically detected in sections from cerebral cortex significantly increased from 5 to 14 mo., but remained unchanged from 14 to 24 mo, while in sections from the left cardiac ventricle these sites of activity remained unchanged during development, and significantly increased during aging. On the other hand the biochemically determined activities of cathepsin B in brain and heart homogenates remained unchanged from 5 to 14 mo., but significantly decreased from 14 to 24 mo. These results suggest that the increase in lipofuscin with age may not be due to an age-wise decline in cathepsin B activity.

ISSN:0304-324X    

DOI:10.1159/000213727

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

From the data of an experiment of selection for increased longevity, a realized heritability of longevity was calculated. The low value of this heritability (3.4%) was very close to values observed in other experiments concerning Drosophila melanogaster wild strains. The error variance of the heritability estimator was calculated through the use of orthogonal contrasts. In this way, it was possible to calculate the confidence interval of the realized heritability. The amplitude of this interval was wide although the size of the sample was large. This shows the difficulty of estimating with precision the heritability of longevity from data obtained in selection experiments.

ISSN:0304-324X    

DOI:10.1159/000213667

出版商:S. Karger AG    

年代:1995

数据来源: Karger