Exposure of Drosophila melanogaster adult males to an atmosphere of O2-N2 (1:1) at 760 Torr resulted in a marked reduction of life span. Among the fine structural changes occurring in the oxygen-poisoned flies, the following were similar to age-related changes: ceroid-lipofuscin accumulation in the visceral organs, sponginess of the brain and accumulation of lamellated dense bodies in the nerve cells. Also, the oxygen-poisoned flies showed a loss of the cytoplasmic membranes of the sperm cells, an alteration which was previously found in y-irradiated, but not in normal senescent, flies. In our opinion, oxygen poisoning of Drosophila may provide a valid model of accelerated aging, at least in regard to peroxidation injury of cell organelles and ceroid-lipofuscin accumulation.

Aging↗

PubMedDate not supplied

A mathematical analysis of the mortality kinetics of Drosophila melanogaster exposed to gamma radiation.

A mathematical model with nonlinear time-varying characteristics has been developed which describes the relationship between the kinetics of natural aging and radiation-induced delayed mortality. Based on this model, it appears that there is an immediate effect of radiation which is continuously, but nonlinearly, increasing in severity. Two phases appear in this variation, corresponding to the two phases (plateau and dying phase) of the mortality curves for control populations. Accordingly, S/E (survival time post-irradiation/further expectation of life) can best be interpreted as an increasing function during the plateau phase of normal mortality curves, which levels off during the ensuing dying phase.

Aging↗

PubMedDate not supplied

Effects of temperature on the life span, vitality and fine structure of Drosophila melanogaster.

The effects of temperature on the aging process have been investigated in approximately 3500 imagoes of male Drosophila melanogaster (Oregon R), with focus on the following parameters: mortality, O2 utilization, vitality (as expressed by negative geotaxis and mating) and fine structural alterations in the abdominal organs and brain. The data on mortality kinetics of flies maintained continuously at 18 degrees, 21 degrees, 27 degrees or 30 degrees C or exposed in succession to 21 degrees and 27 degrees C or vice versa support the concept that life span is temperature dependent. Moreover, these data, together with the increased O2 utilization and accelerated loss of vitality at 21 degrees C as compared with 18 degrees C, suggest that, in agreement with the rate-of-living theory proposed by Alpatov and Pearl in 1929, the flies are living faster at the higher temperature. Fine structural aging changes, like ribosomal loss in the Malpighian tubules and lipofuscin-ceroid accumulation in the midgut cells, seem to be more intense at 27 degrees and at 29 degrees C than at 21 degrees C. Also, the low vitality exhibited through their lives by flies kept at previous exposure through many generations) to 21 degrees C. Flies maintained at 29 degrees C showed a striking degeneration of the brain with an almost complete loss of the cytoplasmic organelles of the nerve cells. This electron microscopic finding lends support to the view that nervous tissue injury (perhaps induced by thermal denaturation of membrane lipoproteins) may play a crucial role in life shortening induced by relatively high temperatures.

Animals↗

PubMedDate not supplied

Thermodynamics of aging in Drosophila melanogaster.

The data on mortality kinetics and decline in functions reported in the preceding article are used to calculate temperature coefficients for the aging process(es) in Drosophila. Different values are found, according to the model chosen to account for the mortality kinetics. The respective implications of three equally suitable models are discussed. Thus, organization parameters on two different levels can be identified: rates of changes assumed to occur at the elementary molecular level, and redundancy factors at a more integrated level. Their temperature coefficients are compared with those of protein denaturations and lipid peroxidation pigment accumulation. It is suggested that elementary molecular processes responsible for aging can indeed be protein denaturations, whereas the known lipid peroxidation pigment accumulation is more likely to be a secondary effect, resulting from a failure of the overall cellular organization at a more integrated, supramolecular, level.

Aging↗

PubMedDate not supplied

Fine-structural changes in the midgut of old Drosophila melanogaster.

Variations of the mitochondrial structure with increasing age are of particular interest because the production of ATP is necessary for most cellular activities. Therefore, a senescent decrease of mitochondrial activity could jeopardize cell survival and function. We combined a statistical with a morphological approach to investigate these changes in mitochondrial size and structure of Drosophila melanogaster. The midgut epithelium is of special interest because previous research shows striking aging changes. Investigations of the mitochondria of flies of three age groups (10, 39, and 65 days) reveal an increase in size as well as in its standard deviation. This is linked to the fact that mitochondrial enlargement occurs especially in the luminal region. Ultrastructural studies show that with increasing age the mitochondria become more osmiophilic, their cristae disarranged, cristae-free areas can also be found, and there is an accumulation of homogeneous, granular and lamellar dense bodies. In addition, an accumulation of virus-like particles, fiber-shaped structures, reticular structures, and dense bodies without a surrounding membrane was found.

Aging↗

PubMedDate not supplied

Senile cataract: a review on free radical related pathogenesis and antioxidant prevention.

Glutathione metabolism plays an essential role in the homeostasis of the lens. Thus, it is not surprising that experimental depletion of this substance leads to a process of lens disorganization similar to senile cataract and that in all types of irreversible cataract there is a decrease in the glutathione content of the lens. Therefore, it may be useful in preventive geriatrics to raise the glutathione concentration of the lens and, since glutathione monoethyl ester can cross the capsule and membranes of the lens, administration of this compound may be the treatment of choice. This could be complemented by long-term administration of small doses of acetylsalicylic acid, in the early stages of the development of cataracts. The data also suggest that, in the 'high lactose absorbers', diets deprived of lactose (in addition to antioxidant administration) may play a role in protecting against cataract development and may even reverse some of the early changes that occur in cataractous lenses. The present review provides a justification for detection of cataract risk factors (high lactose absorption and low antioxidant protection in blood) as well as for preventive and palliative treatment of cataracts by administration of physiological antioxidants.

Journal Article↗

PubMedDate not supplied

An integrated theory of aging as the result of mitochondrial-DNA mutation in differentiated cells.

We maintain that aging of humans and animals derives from a mutation or inactivation (probably followed by endonuclease digestion) of the mitochondrial genome of differentiated cells. This extranuclear somatic mutation hypothesis of aging is based on the finding that mitochondrial DNA (mtDNA) synthesis takes place at the inner mitochondrial membrane near the sites of formation of highly reactive oxygen species and their products, such as lipoperoxides and malonaldehyde. The mtDNA may be unable to counteract the damage inflicted by those by-products of respiration because, in contrast to the nuclear genome, it lacks histone protection and scission repair. Since the mitochondrial genome controls the synthesis of several hydrophobic proteins of the inner mitochondrial membrane, the postulated mutation, inactivation 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 bioenergetic ability, with concomitant senescent loss of physiological performance and eventual death. The above hypothesis is integrated with the concepts of Minot, Pearl and others in order to offer a more comprehensive view of aging.

Journal Article↗

PubMedDate not supplied

Leukocyte function and life span in a murine model of premature immunosenescence.

Aging associates with a decline of physiological functions, including the function of the nervous and the immune system. These aged-related changes occur in various degrees in different members of a mouse outbred population. Accordingly, we have proposed a model of premature immunosenescence in mice, based on the demonstration of premature decline in the behavioral response in a simple T-maze and in several immune functions in Swiss outbred mice. Those mice with a worst (slow) performance in this test (linked to a higher emotional response to stress) show a shorter life span and a decreased immune function when compared to fast mice. In order to provide biomarkers of "biological aging" related to health and survival, the present longitudinal study includes the analysis of several immunological parameters such as, proliferative response to mitogen Con A, NK activity and cytokine (TNFalpha, IL-1beta and IL-2) release by peritoneal leukocytes from female Swiss mice. Slow mice showed a lower proliferative response to Con A, IL-2 and IL-1beta release, an impaired NK activity and an increased TNFalpha production as compared to fast mice. Moreover, the age-associated decline of these functions is more strikingly slow than in fast mice. In summary, we propose the above immunological parameters, that change with aging at a different rate in members of a same population, as useful biomarkers to asses the rate of biological aging in mice.

Aging, Premature↗

PubMedDate not supplied

An update on the oxygen stress-mitochondrial mutation theory of aging: genetic and evolutionary implications.

The acceleration of fixed-postmitotic cell aging by a high metabolic rate and the age related loss of mitochondria found in that cell type led us to propose an oxygen stress-mitochondrial mutation theory of aging, according to which senescence may be linked to mutations of the mitochondrial genome (mtDNA) of the irreversibly differentiated cells. This extranuclear somatic gene mutation concept of aging is supported by the fact that mtDNA synthesis takes place at the inner mitochondrial membrane near the sites of formation of highly reactive oxygen species. Mitochondrial DNA may be unable to prevent the intrinsic mutagenesis caused by those byproducts of respiration because, in contrast to the nuclear genome, it lacks excision and recombination repair. The resulting mitochondrial impairment and concomitant cell bioenergetic decline may cause the senescent loss of physiological performance and may play a key role in the pathogenesis of many age-related degenerative diseases. These concepts are integrated with classic and contemporary hypotheses in a unitary theory that reconciles programmed and stochastic concepts of aging. Thus, it is suggested that cells are programmed to differentiate, and then they accumulate mitochondrial-genetic damage because of their high levels of oxyradical stress and the loss of the organelle rejuvenating power of mitosis.

Aging↗

PubMedDate not supplied

Effects of hypoxia on retinal pigmented epithelium cells: protection by antioxidants.

Age-related macular degeneration and other eye diseases, such as diabetic retinopathy, are probably linked to the effects of oxygen radicals derived from light or metabolic reactions. We have investigated the effects of hypoxia on bovine retinal pigmented epithelial cells (RPE) and the response of these cells to two antioxidants that have previously shown a beneficial action against free radical-linked senescent involution. The main results of the study were as follows: (i) Hypoxia induced apoptotic damage on RPE cells, with LDH leakage and ATP reduction; (ii) both vitamin C (VC) and N-acetyl-cysteine (NAC) treatment protected against hypoxia-induced apoptosis, with less DNA fragmentation. In our opinion, these findings justify further experimental and clinical work to investigate the role of hypoxia in the mechanisms of age-related RPE injury and death as well as the potential of antioxidant administration to prevent or delay retinal degenerative processes caused by oxygen-dependent pathophysiological conditions.

Acetylcysteine↗

PubMedDate not supplied

[Absence of inferior vena cava syndrome as a result of renal-splenic shunt].

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Humans↗