Age (1978-1999)

Aging is accompanied by many changes in immune response, with the most consistent and dramatic alterations occurring within the T cell compartment. Since cytokines are central to immune cell communications, age-associated changes in cytokine production may contribute to these alterations. While data from murine studies suggest a switch from a Th1 (IL-2, IFNγ) to a Th2 (IL-4, IL-6, IL-10) cytokine response, this model has not been as clearly established in humans. In addition, this current review of over 50 studies in humans suggests that age-associated changes in cytokine production are not consistent...

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Heme oxygenase (HO) performs the rate limiting step in heme degradation and is induced by cell injury or stress. We wished to determine if dietary fatty acid composition, increased age and/or an induced oxidative stress would alter the expression of HO-1 (constitutive and inducible isozyme) or of HO-2 (constitutive isozyme), in mouse liver, spleen and brain. Six-and 24-month-old male B6C3F1 mice were fed AIN-76A diets containing either 5% corn oil (CO, moderately unsaturated, n=5 per age group) or 19% menhaden fish oil plus 1% corn oil (FO, highly polyunsaturated, n=20 per age group)...

Chloroform-methanol extracts from rat adrenals at five different ages (2, 6, 12, 18 and 24 months), were studied by fluorescence. After obtaining excitation and emission spectra, fluorescence intensity was measured at 365 nm excitation and 455 emission for all time points of aging. An additional study of lipid peroxidation employing a thiobarbituric acid reaction was made. Fluorescence intensity increased during aging from 16.39 × 10(3) arbitrary units of fluorescence per gram of tissue at 2 months, to 34...

The rate of oxidative phosphorylation was investigated in isolated mitochondria from hindlimb muscles of young (4.5 mo) and old (26.5 mo) male Fischer 344 rats with or without endurance training. Further, the susceptibility of the muscle mitochondria to exogenous reactive oxygen species was examined. State 3 and 4 respiration, as well as the respiratory control index (RCI), were significantly lower in muscle mitochondria from aged vs. young rats (P<0.05), using either the site 1 substrates malate-pyruvate (M-P) and 2-oxoglutarate (2-OG), or the site 2 substrate succinate...

There is an increasing number of elderly patients with glomerulonephritis. A number of reports regarding renal function [1-9] and morphology [10-13] in aged people have been published. However, few studies have been reported on the effect of glomerulonephritis on the kidneys of aged patients. Recently, some articles concerning renal function and histological changes in aged nephritic patients were reported [14]. Several reports about the effects of aging in an experimental kidney disease model [15-23] and on cultured renal cells [22, 24, 25] have been published...

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Cu,Zn superoxide dismutase (Cu,Zn SOD) is one of several anti-oxidant enzymes which defend the cell against damage by oxygen free radicals. Mutations of the SOD1 gene encoding Cu,Zn SOD are found familial amyotrophic lateral sclerosis, a progressive and fatal paralytic disease which is caused by the death of motor neurons in cortex, brainstem and spinal cord. The disease can be reproduced in transgenic mice by expression of mutant human Cu,Zn SOD. Recent studies both in vitro and in vivo suggest that the effect of mutation is to enhance the generation of oxygen radicals by the mutant enzyme...

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Free radicals and other reactive oxygen species are produced in the metabolic pathways of aerobic cells and affect a number of biological processes. Oxidation reactions have been postulated to play a role in aging, a number of degenerative diseases, differentiation and development as well as serving as subcellular messengers in gene regulatory and signal transduction pathways. The discovery of the activity of superoxide dismutase is a seminal work in free radical biology, because it established that free radicals were generated by cells and because it made removal of a specific free radical substance possible for the first time, which greatly accelerated research in this area...

At least seven adult-onset neurodegenerative diseases, including Huntington's disease (HD), are caused by genes containing expanded CAG triplets within their coding regions. The expanded CAG repeats give rise to extended stretches of polyglutamines (Qn) in the proteins expressed by the affected genes. Generally, n ≥40 in affected individuals and ≤36 in clinically unaffected individuals. The expansion has been proposed to confer a "toxic gain of function" to the mutated protein. Poly-Q domains have recently been shown to be excellent substrates of tissue transglutaminase...

We have developed a simple in vitro assay using tissue homogenates that allows detection and characterization of several endogenous proteolytic activities which convert Alzheimer's amyloid precursor protein (APP) to the smaller, carboxy-terminal fragments, postulated to be intermediates in the formation of β-amyloid peptide (Aβ). Incubation at 37°C results in the degradation of transmembrane APP and formation of a mixture of carboxy-terminal containing peptides with mass values of 9-12 kDa. Epitope mapping and electrophoretic comparison with a truncated APP standard showed one of these peptides to contain the entire Aβ sequence...

Cultured fibroblasts are a valuable tool to study many cellular processes and their modification by aging. Fibroblasts are a useful cell type in which to study many diseases, including those of the nervous system, in which a strong genetic component is suspected. Fibroblasts permit the study of multiple, dynamic processes in living cells, while avoiding the effect of the dying process and post-mortem artifacts that limit other approaches. For results to be comparable across time in one laboratory or consistent between laboratories, the detailed culture techniques require meticulous care and replicability...

The exquisite sensitivity of mitochondrial transcription to oxidant stress suggests that chronic, low level oxidative stress may impair mitochondrial gene expression during the aging process. In this study, we assessed the effects of age and of life-prolonging, anti-oxidative dietary restriction (DR) regimens on sensitivity of mitochondrial transcription to oxidant stress. Studies were carried out using liver mitochondria isolated from male Fischer 344 rats of different ages (6, 12, 18, or 24 months) fed ad libitum (AL) or maintained on DR...