Gravity effects on reproduction, development, and aging.
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Aging↗
Biomedical subjects
J Miquel
Publications and source records attributed to J Miquel.
Helminthfauna of Microtus (Microtus) cabrerae (Thomas, 1906) (Rodentia: Arvicolidae) in the Iberian peninsula: faunistic and ecological considerations.
Faunistic and ecological study of parasitic helminths of Microtus (Microtus) cabrerae (Thomas, 1906) (Rodentia: Arvicolidae) in the Iberian Peninsula. 70 specimens have been dissected, coming from 8 enclaves located in three Spanish provinces; 6 species of helminths have been detected (1 Digenetic Trematode, 4 Cestodes and 1 Nematode). Structure of helminthfauna of M. (M.) cabrerae in relation to remaining Iberian Arvicolids and the most conditioning ecological factors of the helminthfauna of the Rodent are analyzed.
Animals↗
Morphological and biochemical examination of Cosmos 1887 rat heart tissue: Part I--Ultrastructure.
Morphological changes were observed in the left ventricle of rat heart tissue from animals flown on the Cosmos 1887 biosatellite for 12.5 days. These tissues were compared to the synchronous and vivarium control hearts. While many normal myofibrils were observed, others exhibited ultrastructural alterations, i.e., damaged and irregular-shaped mitochondria and generalized myofibrillar edema. Analysis of variance (ANOVA) of the volume density data revealed a statistically significant increase in glycogen and a significant decrease in mitochondria compared to the synchronous and vivarium controls. Point counting indicated an increase in lipid and myeloid bodies and a decrease in microtubules, but these changes were not statistically significant. In addition, the flight animals exhibited some patchy loss of protofibrils (actin and myosin filaments) and some abnormal supercontracted myofibrils that were not seen in the controls. This study was undertaken to gain insight into the mechanistic aspects of cardiac changes in both animals and human beings as a consequence of space travel (1). Cardiac hypotrophy and fluid shifts have been observed after actual or simulated weightlessness and raise concerns about the functioning of the heart and circulatory system during and after travel in space (2-4).
Actins↗
[Coronary angioplasty: experience at the University Hospital of Madrid].
The results of 963 consecutive coronary angioplasties, with 1.135 lesions attempted in 816 patients, were prospectively analyzed. Initial angiographic success (residual stenosis less than 50%) was achieved in 1.017 lesions (89.6%), and final success was obtained in 838/963 procedures (87%). Major complications included: emergency surgery in 4 cases (0.4%), acute myocardial infarction in 28 (2.9%), and death during hospitalization in nine (0.9%). Surgical stand-by was required only for cases with vital risk should the attempted vessel occlude. This criteria was present in 230 (23.8%) angioplasties. Coronary angioplasty was performed during the diagnostic procedure in 300 (31.1%) case, with final success in 264 (88%) of them. A exercise test was achieved before the procedure in 419 (50%) successful angioplasties and in 246 (58.7%) of them it was abnormal because of angina (with or without ST depression). After procedure, exercise could be performed in 780 cases (93%), and the result remained unchanged in only 44 (5.6%) (p less than 0.01). At discharge 780 (93%) patients with final success considered themselves clinically improved. In our experience, coronary angioplasty is a good myocardial revascularization technique, with high success, low rate of major complications, and that provides a good clinical outcome. Surgical stand-by may be unnecessary in prost of angioplasty procedures if patients selection is carefully done, also, this approach makes it possible to perform angioplasty at time of diagnostic catheterization.
Adult↗
Effects of aging on respiration, ATP levels and calcium transport in rat liver mitochondria. Response to theophylline.
The concept that aging results in an impairment of mitochondrial biochemistry has been tested on organelles isolated from the liver of 3-4-month-old and 24-month-old rats of the Wistar strain. Our data suggest that aging results in significant decreases in succinate-supported respiration, ATP levels and calcium uptake. When theophylline was added to the incubation mixture, both respiration and calcium uptake were depressed in approximately the same proportion in the mitochondria from old rats, although the mitochondrial ATP of young animals was significantly decreased by this substance.
Adenosine Triphosphate↗
Age-dependent changes in proteins of Drosophila melanogaster.
Several molecular theories of aging postulate that there are age-dependent changes in gene expression and that these changes contribute to the reduction in the viability of senescent cells. High-resolution, semiautomated, quantitative two-dimensional gel electrophoresis of many soluble proteins was used to test this hypothesis in Drosophila. Two-dimensional protein gel patterns were analyzed for each of three age groups of [(35)S]methionine-labeled adult male Drosophila melanogaster, which, except for their spermatocytes, consist entirely of fixed postmitotic cells. Seven relatively abundant polypeptides expressed in middle-aged (28-day-old) flies were absent in both young(10-day-old) and old (44-day-old) flies. Quantitative analyses of an additional 100 polypeptides were carried out by computer-assisted microdensitometry of fluorograms of the gel preparations. These analyses revealed a significant age-related heterogeneity in the quantitative distribution of radiolabel in these proteins. The data indicate that the qualitative pattern of gene expression is identical in young and old flies, but that profound quantitative changes occur in the expression of proteins during the Drosophila life-span.
Aging↗
Long term effects of low doses of 56Fe ions on the brain and retina of the mouse: ultrastructural and behavioral studies.
Eight month old male C57BL6 mice were exposed without anesthesia to whole-body irradiation in circular holders. The mice were tested for behavioral decrements after 0.5 and 50 rads of Fe particle irradiation at 6 and 12 months post irradiation to obtain long term results. A standard maze was used and the animals were timed for completion thereof. A string test also was administered to the mice, testing their ability to grasp and move along a string to safety. The results from animals exposed to 50 rads were significantly different from [correction of fron] control results to p = < .001 in both systems of testing. The hippocampus (believed to be the location of environmental interaction in the brain) and the retina were examined for ultrastructural changes. The ultrastructural changes were similar to those we found in our Cosmos 782, 936 and in our Argon experiments. The mouse data indicate that iron particles were able to induce long term changes in the central nervous system which lead to behavioral impairment.
Animals↗
Age dependent changes in mitochondria.
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Aging↗
The effect of high energy (HZE) particle radiation (40Ar) on aging parameters of mouse hippocampus and retina.
Eight month old C57BL6 mice were exposed (head only) to 0.5 rad or 50 rads of Argon particles at the Lawrence Berkeley Radiation Facility, CA. Neuromotor performance was assessed monthly for six months beginning twelve weeks post-irradiation using a "string test". The decline in motor performance was dose-related and none of the animals was able to complete the task after four months of testing. Morphological changes were monitored six and twelve months post-irradiation by light and electron microscopy. The synaptic density in the CA-1 area of the hippocampus decreased six and twelve months after irradiation. The decrease after twelve months was less than after six months. The width of the outer nuclear layer (ONL) of the retina increased with increasing dose. The number of blood vessels between the ONL and the ganglion layer decreased twelve months after irradiation and this area did not show significant accumulation of age pigment.
Aging↗
A two-step hypothesis on the mechanisms of in vitro cell aging: cell differentiation followed by intrinsic mitochondrial mutagenesis.
Despite vigorous research, there is yet no agreement on the biochemical mechanisms responsible for the loss of replicative potential of diploid cultured cells. In contrast to the program theories of in vitro cell aging, we propose that, as already suggested by Minot in 1907, senescence is the result of cell differentiation. We further maintain that the fundamental cause of cell aging is an instability of the mitochondrial genome because of a lack of balance between mitochondrial repair and the disorganizing effects of oxygen radicals which arise in the respiring mitochondria of terminally differentiated cells. This probably results in intrinsic mitochondrial mutagenesis which may be followed by endonuclease degradation of the altered mitochondrial DNA. Since the mitochondrial genome controls the synthesis of several hydrophobic proteins of the inner mitochondrial membrane, the postulated denaturation or loss of mtDNA will prevent the replication of the organelles. Thus, deprived of the ability to regenerate their mitochondrial populations, the cells will sustain an irreversible decline in their ability to synthesize ATP, with concomitant senescent degradation of physiological performance and eventual death.
Adenosine Triphosphate↗
Ultrastructural findings in the brain of fruit flies (Drosophila melanogaster) and mice exposed to high-energy particle radiation.
Effects of high energy, heavy particle (HZE) radiation were studied in the brain of the fruit fly (Drosophila melanogaster) exposed to argon (40Ar) or krypton (84Kr) ions. In the flies exposed to argon the fluence ranged from 6 X 10(4) to 8 X 10(7) particles/cm2. The insects were killed 35 days after exposure. Extensive tissue fragmentation was observed at the higher fluence employed. At fluences ranging from 5 X 10(6) (one hit/two cell bodies) to 9 X 10(4) (one hit/90 cell bodies) particles/cm2, swelling of the neuronal cytoplasm and focally fragmented membranes was observed. Marked increase of glial lamellae around nerve cell processes was seen at fluences ranging from one hit/six to one hit/135 cell bodies. In the flies irradiated with krypton, the fluences employed were 5.8 X 10(3) and 2.2 X 10(6) particles/cm2. Acute and late effects were evaluated. In the flies killed 36 hours after exposure (acute effects) to either fluence, glycogen particles were found in the neuroglial compartment. The granules were no longer present in flies killed 35 days later (late effects). As in the flies exposed to argon, neuronal swelling and membrane disruption were observed 35 days after exposure to both fluences. From these studies it appears that the Drosophila brain is a useful model to investigate radiation damage to mature neurons, neuroglia, and therefore, to the glio-neuronal metabolic unit. In a separate study, the synaptic profiles of the neuropil in layers II-III of the frontal cerebral cortex of anesthesized adult LAFl mice were quantitatively appraised after exposure to argon (40Ar) particles. The absorbed dose ranged from 0.05 to 5 gray (Gy) plateau. It was determined that the sodium pentobarbital anesthesia per se results in a significant decrease in synaptic profile length one day after anesthetization, with return to normal values after 2-28 days. Irradiation with 0.05-5 Gy argon particles significantly inhibited the synaptic shortening effect of anesthesia at one day after exposure.
Animals↗
Role of metabolic rate and DNA-repair in Drosophila aging: implications for the mitochondrial mutation theory of aging.
The respective roles of respiration rate and DNA repair in determining the life-span of Drosophila melanogaster have been investigated in three wild strains (Oregon R, Domodedov 32, & Swedish C) and two mutants (w/w & w/mei-41 D5). In agreement with the rate of living theory, there was an inverse relation between oxygen consumption and median life-span in flies having normal DNA repair. In contrast, w/mei-41 D5, showed an abnormally low life-span as compared to the controls. The median life-spans for these flies were: Oregon R, 49; Domodedov 32, 46; Swedish C, 35; w/w, 33; and w/mei-41 D5, 22. Furthermore, this mutant also showed significant deficiency in mating fitness and a depressed metabolic rate. These data suggest that the short life-span of the w/mei-41 D5 is a consequence of a specific syndrome unrelated to normal aging and is not the expression of accelerated senescence. It is proposed that DNA repair mechanisms influence adult life-span by their effect on actively dividing progenitor cells during development rather than by modulating senescence of the resulting differentiated cells of the imago during adulthood.
Aging↗
An electron-microscopic study of the brain of the fruit fly, Drosophila melanogaster, exposed to high-LET krypton (84Kr) particle radiation.
Fruit flies (Drosophila melanogaster) were exposed to high-LET krypton (84Kr) ions at low (4.2 rad) and high (1,584 rad) doses and killed to assess acute (36 h post-exposure) and late (35 days post-exposure) effects in the brain by means of electron microscopy. The main findings were: (a) glycogen granules appeared in the neuroglial compartment 36 h after exposure to either dose and were no longer present in flies killed 35 days later, (b) neuronal alterations (swelling and membrane disruption) were observed 35 days after exposure to both doses, (c) changes in the neuroglia (electron-dense masses of concentrically arranged membranous structures) were seen 35 days after exposure. The data are discussed in relation to previous research in the fruit fly using argon (40Ar) charged particles and to other radiation studies performed in the mammalian brain with the view of using the insect brain as a model for detailed study of radiation effects on neurons, neuroglia, and the neuron-neuroglia unit.
Animals↗
Antioxidants, metabolic rate and aging in Drosophila.
In line with the (metabolic) rate-of-living theory of aging, previous work from this laboratory showed that the life-prolonging effect of the antioxidant thiazolidine carboxylic acid (TCA) in Drosophila was paralleled by a similar reduction of the oxygen consumption rate of the flies. To assess the generality of this phenomenon, several life-prolonging antioxidants were dietarily administered to the flies (in standard medium with 1% w/v of tocopherol-stripped corn oil) and their effects on metabolic rate and life span were determined. Respiration rate of groups of continuously agitated flies was measured in the Gilson respirometer. The studied antioxidants were as follows: (the numbers in parentheses are consecutively the antioxidant concentration in the medium in % wt/vol.; mean life span in days; and metabolic rate in microliter O2/mg fly per 24 h): vitamin E (0.4; 46.3; 58.5); 2,4-dinitrophenol (0.1; 45.7; 66.2); nordihydroguaiaretic acid (0.5; 45.6; 69.1); thiazolidine carboxylic acid (0.3; 53.1; 55.8); and control with no antioxidant added (0; 40.7; 73.3). All of these antioxidants at the tested concentrations reduced oxygen consumption rate and increased mean life span; there was a significant negative linear correlation (r = -0.87) between mean life span and metabolic rate. These data suggest that some antioxidants may inhibit respiration rate in addition to their protective effect against free radical-induced cellular damage.
2,4-Dinitrophenol↗
Thiazolidine-4-carboxylic acid, a physiologic sulfhydryl antioxidant with potential value in geriatric medicine.
Thiazolidine-4-carboxylic acid (TC) is a cyclic sulfur amino acid, a condensation product of cysteine and formaldehyde. The chemistry, biological effects and clinical use of TC are reviewed. Extensive animal experiments and studies on human subjects carried out in Europe indicate that a combination of TC and folic acid, 'Folcysteine', has revitalizing effects on age-related biochemical variables of blood and tissues. Further animal studies confirmed the anti-toxic effects of TC, particularly on the liver. The evidence accumulated so far suggests that addition of TC to the diet slows the aging process in mammals and prolongs their life span. On the other hand, findings suggesting that TC caused reverse transformation of tumor cells into normal cells and was effective against human cancers could not be confirmed in additional studies. TC has been clinically used for about 20 yr, mainly in the treatment of liver diseases and related gastrointestinal disturbances. Derivatives of TC with similar applications have been developed. Djenkolic acid is a naturally occurring relative of TC which is abundant in djenkol beans. The toxic effects of djenkolic acid and its possible conversion into TC are discussed.
Aged↗
Effects of simulated increased gravity on the rate of aging of rats: implications for the rate of living theory of aging.
Ever since Pearl proposed the rate of living theory of aging numerous studies have demonstrated its validity in poikilotherms. In mammals, however, satisfactory experimental demonstration is still lacking because an externally imposed increase of basal metabolic rate of these animals (e.g. by placement in the cold) is usually accompanied by general homeostatic disturbance and stress. The present study was based on the finding that rats exposed to slightly increased gravity are able to adapt with little chronic stress but at a higher level of basal metabolic expenditure (increased 'rate of living'). The rate of aging of 17-mth-old rats that had been exposed to 3.14 times normal gravity in an animal centrifuge for 8 mth was larger than of controls as shown by apparently elevated lipofuscin content in heart and kidney, reduced numbers and increased size of mitochondria of heart tissue, and inferior liver mitochondria respiration (reduced 'efficiency': 20% larger ADP: 0 ratio, P less than 0.01; reduced 'speed': 8% lower respiratory control ratio, P less than 0.05). On the other hand, steady-state food intake per day per kg body weight, which is presumably proportional to 'rate of living' or specific basal metabolic expenditure, was about 18% higher than in controls (P less than 0.01) after an initial 2-mth adaptation period. Finally, though half of the centrifuged animals lived only a little shorter than controls (average about 343 vs. 364 days on the centrifuge, difference statistically nonsignificant), the remaining half (longest survivors) lived on the centrifuge an average of 520 days (range 483-572) compared to an average of 574 days (range 502-615) for controls, computed from onset of centrifugation, or 11% shorter (P less than 0.01). Therefore, these results show that a moderate increase of the level of basal metabolism of young adult rats adapted to hypergravity compared to controls in normal gravity is accompanied by a roughly similar increase in the rate of organ aging and reduction of survival, in agreement with Pearl's rate of living theory of aging, previously experimentally demonstrated only in poikilotherms.
Aging↗
Accelerated aging of fasted Drosophila. Preservation of physiological function and cellular fine structure by thiazolidine carboxylic acid (TCA).
Thiazolidine carboxylic acid (TCA) is a natural liver metabolite whose Mg-salt increased lifespan of flies and mice (Miquel and Economos, 1979, Exp. Geront. 14: 279). We studied the physiological and cellular fine structural effects of various concentrations of TCA in the food of male Drosophila. Flies on 0.3% TCA at 27 degrees C had a reduced oxygen consumption rate (about 20% less than controls) at 3 wks of age while their mating capacity and speed of mating were preserved; the flies lived in various experiments 20-30% longer than controls. Apparently TCA improved the metabolic efficiency of the flies (possibly from less "waste" of energy due to improved mitochondrial coupling). However, flies on 0.9% TCA had a reduced mating capacity and lifespan (:toxicity) while at 0.1% TCA was ineffective. A similar dose-response relationship was found in young flies treated with TCA for 1 week and then deprived of food and water, a procedure found to induce accelerated physiological aging. TCA at the 0.3% and 0.6% level reduced the speed of development and the size of the enclosed flies. Electron microscopic investigation of wing muscle showed that 0.3% TCA had a protective effect on cellular fine structure. Though in starved controls (40% survivors after 24 hours of starvation) there was a total absence of glycogen granules, and a striking shrinkage and densification of mitochondria, TCA to a large extent protected muscle cells from these effects of starvation.
Aging↗
Is cell aging caused by respiration-dependent injury to the mitochondrial genome?
Though intrinsic mitochondrial aging has been considered before as a possible cause of cellular senescence, the mechanisms of such mitochondrial aging have remained obscure. In this article we expand on our hypothesis of free-radical-induced inhibition of mitochondrial replenishment in fixed postmitotic cells. We maintain that the respiration-dependent production of superoxide and hydroxyl radicals may not be fully counteracted, leading to a continuous production of lipoperoxides and malonaldehyde in actively respiring mitochondria. These compounds, in turn, can easily react with the mitochondrial DNA which is in close spatial relationship with the inner mitochondrial membrane, producing an injury that the mitochondria may be unable to counteract because of their apparent lack of adequate repair mechanisms. Mitochondrial division may thus be inhibited leading to age-related reduction of mitochondrial numbers, a deficit in energy production with a concomitant decrease in protein synthesis, deterioration of physiological performance, and therefore, of organismic performance.
Animals↗