Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “PROGERIA”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 649 records · Page 36Linked to original sources
PubMed1979

Host-cell reactivation of UV-irradiated adenovirus in Cockayne syndrome.

Measurements of the host-cell reactivation (HCR) of mutagen-treated virus provides a very sensitive tool for detecting abnormal DNA repair. The best example of the utility of HCR studies in the examination of the DNA-repair capacity of human cells has come from studies of cells from the UV-sensitive repair-deficient xeroderma pigmentosum (XP) patients. We have examined the HCR of UV-treated adenovirus type 5 (Ad5) and type 2 (Ad2) in cells from patients with Cocayne syndrome (CS), another sun-sensitive syndrome whose cells also exhibits UV-sensitivity in culture. Comparisons with obligate heterozygotes and normal controls failed to reveal an abnromality in the HCR capacity of the CS cells. As the abnormality in DNA metabolism in CS appears to be in a late step in excision repair, a bypass mechanism may exist in these cells for circumventing the defect in the repair of viral DNA.

Adenoviridae↗
PubMed1980

Increased sensitivity of cell strains from Cockayne's syndrome to sister-chromatid-exchange induction and cell killing by UV light.

Ultraviolet light-induced sister-chromatid exchanges (SCE) and cell killing were investigated in 4 fibroblast cell strains from patients with the sun-sensitive disease Cockayne's syndrome (CS). All 4 CS cell strains proved to be hypersensitive to UV for both of these end-points, but no close correlation between levels of SCE and lethality was observed. Cell strains from two individuals heterozygous for CS were indistinguishable from wild-type.

Cell Survival↗
PubMed1996

Somatic mutagenesis and antimutagenesis in aging research.

Somatic mutagenesis and antimutagenesis are reviewed from the point of view of a gerontologist. Aging can be defined as a set of phenotypes that have escaped the force of natural selection. In mammalian species, aberrations in proliferative homeostasis, including a variety of cancers, are conspicuous examples. The author argues that there is a strong coupling between intrinsic biological aging and the biology of neoplasia. Genomic instability is likely to be a dominant mechanism underlying such coupling. Ongoing experiments from his laboratory and those of collaborators are briefly reviewed. The approaches include: (1) the characterization of a striking progeroid mutation of man, the Werner syndrome, which exhibits a deletor mutator phenotype; (2) the comparative analysis of intragenic and chromosomal mutations in mammalian species of contrasting life span potentials; (3) attempts to synthesize antimutator strains of mice. An emerging generalization is that there is a significant degree of species specificity in the patterns of somatic mutation in aging mammals.

Aging↗
PubMed1990

Growth properties and in vitro life span of Alzheimer disease and Down syndrome fibroblasts. A blind study.

A blind study was set up to examine the in vitro growth characteristics of skin fibroblasts from 2 individuals with and 9 at risk for familial Alzheimer disease, 4 individuals with sporadic Alzheimer disease, 18 with Down syndrome as well as 5 younger and 6 older controls. Several variables (biopsy size, number of explants, medium, passage procedure) were standardized. Two growth characteristics were examined quantitatively: (i) the actual in vitro replicating life span was determined by counting the number of cells plated the previous week at 500,000 cells/flask (cumulative population doublings); and (ii) the growth potential was examined by a colony size distribution assay. A difference from the age-matched controls in the growth characteristics of skin fibroblasts was only observed for two patients with and one older individual at risk for familial Alzheimer disease. The growth properties of skin fibroblast cultures from patients with sporadic Alzheimer disease or Down syndrome were not at variance with their age-matched controls. The decrease in the growth potential observed in the familial Alzheimer disease fibroblasts is however modest and needs confirmation. It is clear that the growth properties of skin fibroblasts, as examined in this study, do not provide a good marker for any form of Alzheimer disease, nor do they provide an appropriate in vitro system to study factors which may contribute to the etiopathogenesis of Alzheimer disease or Down syndrome.

Adult↗
PubMed1991

Elevated concentrations of beta-nerve growth factor in selected tissues from senescence-accelerated mice (SAM-P/8).

Levels of the beta-subunit of nerve growth factor (beta-NGF) were determined in various tissues from senescence-accelerated mice (SAM-P/8) and compared with those from senescence-resistant control mice (SAM-R/1) at 4 months of age. (1) In SAM-P/8, the testis was 30% larger in terms of wet weight than that from SAM-R/1, whereas the adrenal glands from males and females were smaller than those from the respective controls by 45% and 20%, respectively. (2) About 70% of SAM-P/8 individuals had high concentrations of testosterone in serum (greater than 5ng/ml). (3) In SAM-P/8, endogenous levels of beta-NGF were significantly higher in the adrenal gland (20 and 7 times higher on average in males and females, respectively), in the thymus (100 and 5 times higher in males and females, respectively) and in the testis (500 times higher) than those in the control tissues. In other tissues there were little or no differences in terms of levels of beta-NGF. (4) Morphological changes in the adrenal gland, thymus and testis of SAM-P/8 mice were not as marked as expected from the elevated levels of beta-NGF in these tissues. (5) These results show that, in SAM-P/8 mice at 4 months of age, an elevation in the endogenous level of beta-NGF has already occurred in some peripheral tissues before senescence becomes accelerated.

Adrenal Glands↗
PubMed1993

Age changes in visceral content of glutathione in the senescence accelerated mouse (SAM).

Free radical formation is known to play a role in the aging processes. However, it is still disputable whether the scavengers of free radicals including glutathione (GSH) decrease during aging. The senescence accelerated mice (SAM) are known to show age-related disorders. Some of these syndromes were thought to be closely associated with oxidative damages. Using the two strains of SAM, SAM-R/1 and SAM-P/2, we examined age-related changes in GSH content in the tissues and its oxidation. In the eye, GSH levels were significantly decreased at the age of 16 months in SAM-P/2 and female SAM-R/1. The ratio of oxidized glutathione to total GSH increased, indicating GSH may play an important role in the eyes. But there were no remarkable age-related changes in GSH contents of other tissues such as liver, kidney and lung in both SAM-R/1 and SAM-P/2. These data suggest that the GSH level of the tissues in general can not be a proper indicator for senescence.

Aging↗
PubMedDate not supplied

Proliferation-dependent regulation of DNA glycosylases in progeroid cells.

The regulation of the base excision repair enzymes uracil DNA glycosylase and hypoxanthine DNA glycosylase was examined in 2 different progeroid cell strains. The immunoreactivity of the uracil DNA glycosylase in progeroid cells was examined by enzyme linked immunosorbent assay (ELISA) and by immunoblot analysis. The enzyme was recognized in a quantitative manner by 2 different anti-human uracil DNA glycosylase monoclonal antibodies in the ELISA. Western blot analysis identified a glycosylase protein of Mr = 37,000. In randomly proliferating progeroid cells, the uracil DNA glycosylase was enhanced 3-fold during cell growth. In synchronous cells, uracil DNA glycosylase and hypoxanthine DNA glycosylase were induced with an extent of induction (5-6-fold) comparable to that observed for normal human cells. Further, the activity of each base excision repair enzyme was enhanced with a comparable temporal sequence prior to the induction of DNA synthesis and DNA polymerase activity. These results indicate a normal cell cycle regulation of base excision repair in progeroid cells.

Antibodies, Monoclonal↗
PubMed1995

DNA damage, mutation and fine structure DNA repair in aging.

The primary focus of this review is on correlations found between DNA damage, repair, and aging. New techniques for the measurement of DNA damage and repair at the level of individual genes, in individual DNA strands and in individual nucleotides will allow us to gain information regarding the nature of these correlations. Fine structure studies of DNA damage and repair in specific regions, including active genes, telomeres, and mitochondria have begun. Considerable intragenomic DNA repair heterogeneity has been found, and there have been indications of relationships between aging and repair in specific regions. More studies are necessary, however, particularly studies of the repair of endogenous damage. It is emphasized that the information obtained must be viewed from a perspective that takes into account the total responses of the cell to damaging events and the inter-relationships that exist between DNA repair and transcription.

Aging↗
PubMed2005

Genetic modulation of senescent phenotypes in Homo sapiens.

Single-gene mutations can produce human progeroid syndromes--phenotypes that mimic usual or "normative" aging. These can be divided into two classes--those that have their impacts upon multiple organs and tissues (segmental progeroid syndromes) and those that have their major impacts upon a single organ or tissue (unimodal progeroid syndromes). The prototypic example of the former is the Werner syndrome, a condition caused by mutations of the RecQ family of DNA helicases. Research on the Werner syndrome and a surprising number of other progeroid syndromes support the importance of the maintenance of genomic stability as a partial antidote to aging. The prototypic examples of the latter are Alzheimer type dementias. The three gene products that cause rare autosomal-dominant early-onset varieties of these disorders all participate in the modulation of the beta amyloid precursor protein. They thus support the importance of the maintenance of proper protein processing and folding as a partial antidote to aging.

Aging↗
PubMedDate not supplied

Scleroderma and pseudo-scleroderma: uncommon presentations.

Scleroderma is characterized by major clinical symptoms, but a number of unrelated disease may mimic these features more or less completely. Even scleroderma itself sometimes presents in an unusual manner. This article deals with uncommon presentations of true scleroderma and its variants and pseudo -scleroderma diseases.

Amyloidosis↗
PubMed2006

Genetics of proliferative aging.

Human lifespan is limited by aging of both mitotic and post-mitotic cells. These two forms of aging may occur by distinct or overlapping mechanisms. Telomere erosion has been shown to limit the proliferative lifespan of human somatic cells. Other vertebrates, such as mice, possess robust telomerase activity in most cell types and their somatic cells display finite replicative lifespans as a consequence of other forms of macromolecular damage. Genetic analysis in humans, mice and yeast has provided clues regarding pathways that may affect a cell's replicative lifespan. In addition, analysis of the means by which germ cells maintain their effervescent character may provide a deeper understanding of how replicative aging occurs in somatic cells.

Animals↗
PubMed2006

Protein modification in aging: an update.

Post-translational modifications of proteins are an important biologic tool for the production of various protein species from a single gene, which may vary in conformation, function, biologic half-life and complex formation with other proteins. The present minireview summarizes a few selected research observations important for the role of post-translational modifications in biologic aging and age-related diseases, including farnesylation, methylglyoxal-derivatization, transglutaminase pathways and the formation of 3-nitrotyrosine and 2-oxo-histidine in vivo.

Aging↗
PubMed2006

Aging and the ubiquitinome: traditional and non-traditional functions of ubiquitin in aging cells and tissues.

Ubiquitination of endogenous proteins is one of the key regulatory steps of protein degradation followed by regulation of proteasome activity. During the last years evidence has increased that proteasome activity is decreased during the aging process in various model systems and that these changes might be causally related to aging and aging associated diseases. Since in most instances ubiquitination is the primary event in target selection, the system of ubiquitination and deubiquitination might be of similar importance. Furthermore, ubiquitination and proteasomal degradation are not completely congruent, since ubiquitination also confers functions different from giving "the kiss of death" to proteins. Depending on mono- and polyubiquitination and on how ubiquitin chains are linked together, ubiquitination is involved in transcriptional regulation, receptor internalization, DNA repair, and stabilization of protein complexes. This review is therefore the first to summarize the current knowledge regarding the ubiquitinome and the underlying ubiquitin ligases and deubiquitinating enzymes in replicative senescence, tissue aging as well as in segmental progeroid syndromes and to discuss potential causes and consequences for aging.

Aging↗