Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The fidelity of protein synthesis was measured in human diploid skin fibroblasts as a function of passage level ("aging in vitro") and physiological age of tissue donor ("aging in vivo") using two different test systems. First, in cell-free extracts the ratio of delta leu/delta phe incorporation into peptide linkage following in the latter case using cells derived from elderly normal donors and from subjects with the premature aging disorders of Hutchinson-Gilford progeria and the Werner syndrome. Similar results were obtained using a second system of intact cells whereby histidine starvation induces quantifiable satellite spots resolved by two dimensional electrophoresis on polyacrylamide gels on the acidic side of the native actin species due to substitution of the neutral amino acid glutamine for the basic histidine. In fact, error frequencies appeared to decrease during aging in vitro, likely due to selection for clonal subpopulations with the highest fidelity of protein synthesis. The only increases were seen in the intact cell system where SV40-transformed cells showed a three-to-five fold greater error frequency compared to nontransformed fibroblasts. In total, these data fail to support the error catastrophe theory of cellular aging.
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PMID:Protein synthetic fidelity in aging human fibroblasts. 408 61

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.
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PMID:Protein synthetic errors do not increase during aging of cultured human fibroblasts. 624 12

Werner syndrome (WS) is a rare autosomal recessive genetic disorder causing premature aging and rare cancers. A gene responsible for WS (WRN) encodes a protein with 1432 amino acids (a.a.) homologous to the E. coli RecQ-type DNA helicase. Transcriptional activation facilitated nucleolar localization of human WRN protein (hWRNp) and serum starvation induced translocation of hWRNp from the nucleoli to the nucleoplasm in human cultured cells, suggesting a nucleolar-nucleoplasm trafficking of hWRNp depending on transcriptional state. Mutant hWRNp lacking the C-terminal 30 a.a. residues (Delta1403-1432) failed to localize in the nucleolus, whereas Delta1405-1432 can migrate into the nucleolus. Here we identify a region putative for nucleolar localization signal (NoLS) containing a sequence of two positively charged amino acids (Arg(1403)-Lys(1404)) in the C-terminal area of hWRNp. By contrast, the mouse homolog (mWRNp) exists only in the nucleoplasm. We show that the inability of mWRNp to migrate into the nucleolus is due to a difference of a sequence in the region corresponding to the NoLS of hWRNp. In addition, mouse cells cannot recognize the NoLS of hWRNp. Our study suggests that defect in nucleolar function of hWRNp may be linked to the premature aging which is not observed in mWRN(-/-) mice.
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PMID:Diverged nuclear localization of Werner helicase in human and mouse cells. 1142 Jun 65

Reduced autophagy may be associated with normal and pathological aging. Here we report a link between autophagy and Werner protein (WRNp), mutated in Werner syndrome, the human premature aging Werner syndrome (WS). WRN mutant fibroblast AG11395 and AG05229 respond weakly to starvation induced autophagy compared to normal cells. While the fusion of phagosomes with lysosome is normal, WS cells contain fewer autophagy vacuoles. Cellular starvation autophagy in WS cells is restored after transfection with full length WRN. Further, siRNA mediated silencing of WRN in the normal fibroblast cell line WI-38 results in decreased autophagy and altered expression of autophagy related proteins. Thus, our observations suggest that WRN may have a role in controlling autophagy and hereby cellular maintenance.
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PMID:Transient overexpression of Werner protein rescues starvation induced autophagy in Werner syndrome cells. 2525 4