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 703 records · Page 39Linked to original sources
PubMed1980

Protein synthetic errors do not increase during aging of cultured human fibroblasts.

To test the error catastrophe theory of aging we determined the error frequency of protein synthesis in several strains of cultured human fibroblasts at early and late passage. Error rates were calculated from analysis of native and substituted actins on two-dimensional gels of cellular proteins after induction of mistranslation by histidine starvation in the presence of histidinol. Early-passage cells from fetal, young, and old donors and cells from subjects with the Hutchinson-Gilford and Werner syndromes of accelerated aging had similar error frequencies. Late-passage cells from fetal, young, and old normal donors had similar or lower error frequencies than corresponding early-passage cells. No correlation was observed between error frequency, donor age, or maximal life span in vitro. We also examined an immortal cell line, simian virus 40-transformed W138 fibroblasts. These cells had a significantly elevated rate of mistranslation (2.8 +/- 0.2 x 10(-4))(+/- SEM) compared to their untransformed counterpart WI38 (0.6 +/- 0.1 X 10(-4)) or all diploid cells combined (1.1 +/- 0.1 x 10(-4)). Taken together, the data fail to support the error catastrophe theory of aging.

Actins↗
PubMed1990

A genetic defect in the biosynthesis of dermatan sulfate proteoglycan: galactosyltransferase I deficiency in fibroblasts from a patient with a progeroid syndrome.

A small proteoglycan that contains only a single dermatan sulfate chain is the main proteoglycan synthesized by skin fibroblasts. Fibroblasts from a patient with progeroidal appearance and symptoms of the Ehlers-Danlos syndrome have a reduced ability of converting the core protein of this proteoglycan into a mature glycosaminoglycan chain-bearing species. This abnormality is the consequence of a deficiency in galactosyltransferase I (xylosylprotein 4-beta-galactosyltransferase; EC 2.4.1.133), which catalyzes the second glycosyl transfer reaction in the assembly of the dermatan sulfate chain. The glycosaminoglycan-free core protein secreted by the patient's fibroblasts bears an unsubstituted xylose residue. The mutant enzyme is abnormally thermolabile. Preincubation of fibroblasts at 41 degrees C leads to a further reduction in the production of mature proteoglycan and affects the capacity for glycosaminoglycan synthesis on p-nitrophenyl beta-D-xyloside more strongly in the mutant than in control cells.

Carbohydrate Sequence↗
PubMed1999

Molecular basis for the progeroid variant of Ehlers-Danlos syndrome. Identification and characterization of two mutations in galactosyltransferase I gene.

Progeroid type Ehlers-Danlos (E-D) syndrome was reported to be caused by defects in galactosyltransferase I (EC 2.4.1.133), which is involved in the synthesis of common linkage regions of proteoglycans. Recently, we isolated cDNA of the galactosyltransferase I (XGalT-1) (Okajima, T., Yoshida, K., Kondo, T., and Furukawa, K. (1999) J. Biol. Chem. 274, 22915-22918). Therefore, we analyzed mutations in this gene of a patient with progeroid type E-D syndrome by reverse transcription polymerase chain reaction and direct sequencing. Two changes of G and T to A and C at 186 and 206, respectively, were detected. Then, we determined the genomic DNA sequences encompassing the A186D and L206P mutations, revealing that the unaffected parents and two siblings were heterozygous for either one of the two different mutations and normal, while the patient had both of two different mutant genes. Enzymatic functions of cDNA clones of XGalT-1 containing the individual mutations were examined, elucidating that L206P clone completely lost the activity, while A186D retained approximately 50% or 10% of the activity when analyzed with extracts from cDNA transfectant cells or recombinant soluble enzymes, respectively. Moreover, L206P enzyme showed diffuse staining in the cytoplasm of transfectant cells, while the wild type or A186D clones showed Golgi pattern. These results indicated that the mutations in XGalT-1 were at least one of main molecular basis for progeroid type E-D syndrome.

Amino Acid Sequence↗
PubMed2004

Lack of peroxisomal catalase causes a progeric phenotype in Caenorhabditis elegans.

Studies using the nematode Caenorhabditis elegans as a model system to investigate the aging process have implicated the insulin/insulin-like growth factor-I signaling pathway in the regulation of organismal longevity through its action on a subset of target genes. These targets can be classified into genes that shorten or extend life-span upon their induction. Genes that shorten life-span include a variety of stress response genes, among them genes encoding catalases; however, no evidence directly implicates catalases in the aging process of nematodes or other organisms. Using genetic mutants, we show that lack of peroxisomal catalase CTL-2 causes a progeric phenotype in C. elegans. Lack of peroxisomal catalase also affects the developmental program of C. elegans, since Deltactl-2 mutants exhibit decreased egg laying capacity. In contrast, lack of cytosolic catalase CTL-1 has no effect on either nematode aging or egg laying capacity. The Deltactl-2 mutation also shortens the maximum life-span of the long lived Deltaclk-1 mutant and accelerates the onset of its egg laying period. The more rapid aging of Deltactl-2 worms is apparently not due to increased carbonylation of the major C. elegans proteins, although altered peroxisome morphology in the Deltactl-2 mutant suggests that changes in peroxisomal function, including increased production of reactive oxygen species, underlie the progeric phenotype of the Deltactl-2 mutant. Our findings support an important role for peroxisomal catalase in both the development and aging of C. elegans and suggest the utility of the Deltactl-2 mutant as a convenient model for the study of aging and the human diseases acatalasemia and hypocatalasemia.

Aging↗
PubMed2000

The establishment of telomerase-immortalized cell lines representing human chromosome instability syndromes.

The limited life span of normal human cells represents a substantial obstacle for biochemical analysis, genetic manipulation and genetic screens. To overcome this technical barrier, immortal human cell lines are often derived from tumors or produced by transformation with viral oncogenes such as SV40 large T antigen. Cell lines produced by these approaches are invariably transformed, genomically unstable and display cellular properties that differ from their normal counterpart. It was recently shown that the ectopic expression of hTERT, encoding the catalytic subunit of human telomerase, can extend the life span of normal human cells without causing cellular transformation and genomic instability. In the present study, we have used hTERT to extend the life span of normal human skin fibroblasts derived from patients afflicted with syndromes of genomic instability and/or premature aging. Our results show that hTERT efficiently extends the life span without altering the characteristic phenotypic properties of the cells. Thus, the ectopic expression of telomerase represents a major improvement over the use of viral oncogenes for the establishment of human cell lines.

Abnormalities, Multiple↗
PubMed1997

Aging and cancer: issues of basic and clinical science.

The majority of patients with cancer in the United States are more than 70 years old. Despite the increased understanding of the molecular bases for both oncogenesis and aging, the overlap of cancer and aging at that level remains a wide-open research domain. Similarly, at the clinical level, there is also an increased awareness of the need for more information about the influence of host age on the development of tumors, on the growth and spread of the disease, and on treatment expectations. In this review, we have attempted to frame questions regarding cancer and aging from the perspective of biogerontology and geriatric medicine. An increased effort to address the issues of aging is of paramount importance at all levels of cancer investigation.

Adolescent↗
PubMed1982

Premature aging in female alcoholics. A neuropsychological study.

The hypothesis of premature aging in middle-aged female alcoholics was tested by comparing their level pattern of neuropsychological test performance with age-equated nonalcoholic females and elderly nonalcoholic women. Alcoholics had significantly poorer performance on the tests than nonalcoholic peers but performed significantly better than the elderly. A subsample of more severe alcoholics was not significantly different from the elderly in level of performance although they were approximately 20 years younger. However, there were no differences among the groups in pattern of test performance. The data on level of performance partially support the hypothesis of premature aging in alcoholics. Stronger support would be attained if it were demonstrated that the alcoholics and elderly have a similar impairment in the neuropsychological processes eventuating in lowered performance.

Adult↗
PubMed1977

Leprechaunism (Donohue's syndrome) in a low birth weight infant.

A 910 gm infant with leprechaunism, the smallest reported infant with this syndrome, was described. Marked discrepancies were noted between gestational age as assessed by physical examination, bone and dental roentgenographic studies, and renal histology. Radiographic and pathologic features of this syndrome were discussed. Failure to thrive characterized the course of this infant despite adequate caloric intake. The precarious nature of these infants and difficulties encountered in obtaining adequate studies to delineate the cause of this syndrome were emphasized.

Abnormalities, Multiple↗
PubMedDate not supplied

Gastrointestinal complications of spinal cord injury.

The incidence, nature, and radiographic features of gastrointestinal complications encountered in a group of 567 consecutive spinal-cord-injury patients are reported. Eighty-seven episodes of gastrointestinal complications developed in 63 (11%) patients. During the first month postinjury, these complications consisted of ileus, gastric dilatation, the body cast syndrome, peptic ulcer disease, and pancreatitis. More chronically these patients presented with fecal impactions, peptic ulcer disease, the superior mesenteric artery syndrome, hepatitis, amyloidosis, and the precocious appearance of diverticulosis, hiatus hernia, and gastroesophageal reflux. Radiographic findings were diagnostic in the majority of cases and aided in the early diagnosis of these potentially life-threatening complications.

Adolescent↗
PubMed1997

A probable case of Wiedemann-Rautenstrauch syndrome or neonatal progeroid syndrome and review of the literature.

A boy with features suggesting the diagnosis of Wiedemann-Rautenstrauch syndrome (WRS) or neonatal progeroid syndrome is presented. Abnormal findings included a generalized virtual absence of subcutaneous fat, sparse scalp hair, prominence of veins and muscles, a large and persistent anterior fontanelle and facial dysmorphism (triangular aged face, prominent eyes and scalp veins). Until now, only 13 cases (including one prenatal diagnosis) of this syndrome have been described. Since the borderlines of this syndrome are not very exact, we reviewed the previous reports in order to further delineate this rare syndrome.

Adipose Tissue↗