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Biomedical subjects

J Miquel

Publications and source records attributed to J Miquel.

At least 19 recordsLinked to original sources
PubMed1992

Oxygen-induced mitochondrial damage and aging.

Although the views of Harman and Gerschman provide a reasonable explanation for many of the effects of aging, they fail to explain why many cell types, from amoebae to mammalian spermatogonia, do not show a time-related involution, while other cells (especially the neurons) change with age. We feel that a better understanding of senescence (from the molecular to the organ and organismic levels) can be gained by integrating the free radical theory of aging with the classic concepts of Minot and Pearl on the role of cell differentiation and metabolic rate in, respectively, triggering and pacing senescence. In agreement with the above, we maintain that aging is the non-programmed but unavoidable "side effect" of oxy-radical damage to the membrane and genome of the mitochondria of irreversibly differentiated cells. If oxy-radical damage to mtDNA occurs, it will block the rejuvenation of the mitochondrial population by the process of organelle division, thus leading to bioenergetic decline and cellular death.

Aging↗
PubMed1992

Changes with aging and physical exercise in ascorbic acid content and proliferative response of murine lymphocytes.

Ascorbic acid content and lymphoproliferative response to phytohemagglutinin were measured in lymphocytes from axillary nodes, spleen and thymus of young (15 +/- 2 weeks) and old (60 +/- 5 weeks) BALB/c mice. Ascorbic acid content in lymphocytes from spleen and thymus was found to be significantly higher and the lymphoproliferative response in the three immunocompetent organs significantly lower in old mice as compared to young mice. Moreover, young and old BALB/c mice were required to maintain a swimming activity until exhaustion (exhaustive exercise) or 90 min of swimming each day for a total of 20 days (continuous exercise). In both young and old mice the stress produced by exhaustive exercise and confirmed by the existence in serum of significantly increased levels of corticosterone compared to controls, caused a significant decrease in ascorbic acid content as well as in lymphoproliferative response. Continuous exercise, characterized by the presence in serum of significantly decreased levels of corticosterone compared to controls, produced the most significant decrease in ascorbic acid content from young and old murine lymphocytes. Moreover, this exercise resulted in a significant increase in lymphoproliferative response. Our results suggest that aging results in an increase in the ascorbic acid content of lymphocytes accompanied by a decline in the lymphoproliferative response in old BALB/c mice.

Aging↗
PubMed1992

Effect of aging on metabolic zonation in rat liver: acinar distribution of GSH metabolism.

The effect of age on the glutathione antioxidant system and its acinar distribution in rat liver was studied. GSH/GSSG ratio in blood and liver was lower in old than in young rats. Hepatic glutathione peroxidase and glutathione S-transferase activities were higher in old than in young rats, whereas hepatic gamma-glutamyl transpeptidase activity was lower in old than in young rats. Glutathione reductase and glucose-6-phosphate dehydrogenase activities did not change with age in rat liver. Total glutathione levels and glutathione peroxidase activity were higher in periportal than in perivenous areas of young rats, but this heterogeneous distribution did not occur in old rats. No change with age was found in hepatic zonation of glutathione reductase and glucose-6-phosphate dehydrogenase.

Aging↗
PubMed1992

An update on the mitochondrial-DNA mutation hypothesis of cell aging.

Our electron microscopic study of aging insects and mammals suggests that metazoan senescence is linked to a gradual process of mitochondrial breakdown (and lipofuscin accumulation) in fixed postmitotic cells. This led us to propose in the early 1980s an oxyradical-mitochondrial DNA damage hypothesis, according to which metazoan aging may be caused by mutation, inactivation or loss of the mitochondrial genome (mtDNA) in irreversibly differentiated cells. This extranuclear somatic gene mutation concept of aging is in agreement with the fact that mtDNA synthesis takes place at the inner mitochondrial membrane near the sites of formation of highly reactive oxygen species and their products. Mitochondrial DNA may be unable to counteract the damage inflicted by those by-products of respiration because, in contrast to the nuclear genome, it lacks excision and recombination repair. Since mtDNA contains the structural genes for 13 hydrophobic proteins of the respiratory chain and ATP synthase as well as mitochondrial rRNAs and tRNAs, damage to this organellar genome will decrease or prevent the 'rejuvenation' of the mitochondria through the process of macromolecular turnover and organelle fission. Thus deprived of the ability to regenerate their mitochondria, the fixed postmitotic cells will sustain a decrease in the number of functional organelles, with resulting decline in ATP production. At higher levels of biological organization, this will lead to a loss in the bioenergetic capacity of cells, with concomitant decreases in ATP dependent protein synthesis and specialized physiological function, thus paving the way for age related degenerative diseases. The above concept is supported by a wealth of recent observations confirming the genomic instability of mitochondria and suggesting that animal and human aging is accompanied by mtDNA deletions and other types of injury to the mitochondrial genome. Our hypothesis of mtDNA damage is integrated with the classic concepts of Weissman and Minot in order to provide a preliminary explanation of the evolutionary roots of aging and reconcile the programed and stochastic views of metazoan senescence.

Animals↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1990

[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↗
PubMed1988

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↗
PubMed1986

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↗
PubMed1985

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↗
PubMed1979

Quantitative analysis of mating behavior in aging male Drosophila melanogaster.

Dynamic changes in quantitative aspects of mating behavior of the male fruit fly as its life unfolds, from eclosion through maturity (peak performance) and "physiological death" (loss of fertility followed by complete loss of ability to mate), towards actual death, have been identified in this work by observations and measurements on 28 male fruit flies of the Oregon R strain studied individually. At weekly sessions from the first day of their imaginal life until their natural death, each fly was given the opportunity to mate with up to three virgin females during a one-hour period. Length of the latency period of each accomplished mating and duration of copulation were recorded. After mating the females were allowed to lay eggs for 24 hours and the number of offspring was counted 26 days later. The period between 1 and 4 weeks of age is characterized by peak and fairly constant performance: multiple matings, short latencies, long durations of copulation, and high degree of fertility (number of offspring); then a decline sets in, in some measures slower than in others, as the flies age. Large intra- and inter-individual variabilities were, however, found which obscure possible correlations between individual measures of mating ability and length of life. At the individual level, a preliminary analysis showed a good correlation (r = 0.80 and 0.79) between life span and week of last mating (onset of impotence) or week of last fertile mating (onset of sterility). At the population level it was found that a number of measures, i.e. number of remaining maters at each age, number of remaining fertile maters and total number of matings, had an age-course similar to survivorship but anticipated it by 4--6 weeks. Other measures, such as number of multiple matings and number of offspring declined with age faster than survivorship.

Aging↗