Effect of Aging on the Components of the Protein Synthesis System

Webster, George C.

doi:10.1007/978-3-642-70853-4_16

Cited by 15 publications

(6 citation statements)

References 28 publications

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“…Experiments in other systems support the idea that EF-la activity is controlled at the transcriptional level. A decrease in EF-la mRNA was observed in aging rats (6) and in differentiating mouse erythroleukemia cells (30). Cavallius et al (31) observed that both EF-la protein and EF-la catalytic activity decreased in aging fibroblasts but remained constant in simian virus 40-transformed "immortal" fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

“…According to the program theory of aging, the longevity of animal species, as well as the lifespan of their cells in culture, is determined by genetically controlled processes similar to those that control early development. Several attempts have been made to demonstrate the existence oflongevity-determining genes (1)(2)(3)(4)(5) A decrease in the rate of protein synthesis with advancing age has been observed in many animals species (6)(7)(8)(9). The importance of this decrease in protein turnover is still under debate (10).…”

mentioning

confidence: 99%

“…The importance of this decrease in protein turnover is still under debate (10). Experiments carried out by Webster (6,11,12) suggested that the age-related decline in protein synthesis in Drosophila melanogaster might result from decreased tran-MATERIALS AND METHODS Flies. The transgenic D. melanogaster lines constructed by Shepherd et al (14) were used: E flies contain a P-element with the EF-la cDNA under control of the hsp7O promoter; C flies contain the same P element without EF-la cDNA.…”

mentioning

confidence: 99%

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Protein synthesis elongation factor EF-1 alpha expression and longevity in Drosophila melanogaster.

Shikama

Ackermann

Brack

1994

Proc. Natl. Acad. Sci. U.S.A.

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It has been proposed that the decline in protein synthesis observed in aging organisms may result from a decrease in elongation factor EF-la. Transgenic Drosophila melanogaster flies carrying an additional copy of the EF-la gene under control of a heat-inducible promoter have an extended lifespan, further indicating that the EF-la gene may play an important role in determining longevity. To test this hypothesis, we have quantitated EF-1amRNA, EF-la protein, and the EF-la complex-formation activity in these transgenic flies. Furthermore, we have tested whether the transgene construct is functiona-i.e., whether transgenic mRNA is induced when flies are grown at higher temperature. The results show that although there is a clear difference in mean lifespan between the EF-la transgenic (E) flies and the control transgenic (C) flies, E flies do not express more EF-la protein or mRNA than C flies kept at the same experimental conditions. Although the transgene can be induced when E flies are heat-shocked at 3rC, transgenic mRNA is not detectable in E flies aged at 29°C. In both lines, the loss in catalytic activity with age is the same. We conclude that the E flies examined here do not live longer because of overexpressing the EF-1a gene.scription of the EF-la gene. The eukaryotic polypeptidechain-elongation factor EF-la is a GTP-binding protein that catalyzes the binding of aminoacyl-tRNA to the ribosome (13). Based on Webster's experiments, Shepherd et al. (14) addressed the question of whether expression of the EF-la gene may be directly involved in determining the lifespan of the fruit fly. They transformed Drosophila with a P-element vector containing a cDNA copy of the EF-la gene under control of the inducible hsp7O (70-kDa heat shock protein) gene promoter. At 250C the flies carrying the EF-la P element (E flies) lived significantly longer than the flies carrying a control P element (C flies). This difference in mean lifespan was increased when flies were kept at 29.50C. The authors concluded that the heat-induced overexpression of the EF-la gene led to increased lifespan of the flies and thus that there might be a positive correlation between the expression of the EF-la gene and longevity. Their results suggested that an important aging control might be exerted at the level of transcription of the EF-la gene. We have tested this hypothesis by measuring the expression of EF-la in these transgenic E and C flies both at the mRNA and at the protein level. The lifespan of each species, including man, is different, but genetically defined. According to the program theory of aging, the longevity of animal species, as well as the lifespan of their cells in culture, is determined by genetically controlled processes similar to those that control early development. Several attempts have been made to demonstrate the existence oflongevity-determining genes (1-5), but nothing is known about possible targets for such genes at the cellular or at the molecular level. Most higher organisms contain mitotic as well as p...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Protein synthesis elongation factor EF-1 alpha expression and longevity in Drosophila melanogaster.

Shikama

Ackermann

Brack

1994

Proc. Natl. Acad. Sci. U.S.A.

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“…Few data are available on the study of spe cific proteins involved in this process. Several groups investigating the role of protein syn thesis in aging have used the insect model [re viewed in 4], In systematic studies on all steps involved in protein synthesis, carried out in Drosophila melanogaster, Webster [7,8] has concluded that the age-related decrease in protein synthesis is due to the transcriptional down-regulation of the gene coding for pep tide synthesis elongation factor HF-la. EF-la is a component of the EF-1 complex that includes other subunits (3, y, and 8.…”

mentioning

confidence: 99%

Changes in the Expression of Genes Involved in Protein Synthesis during <i>Drosophil</i><i>a</i> Aging

Shikama

Brack²

1996

Gerontology

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A characteristic feature of aging organisms is their loss in homeostatic functions, including the ability of protein synthesis and turnover. It has been proposed that in senescent Drosophila melanogaster the peptide synthesis elongation factor (EF) EF-1α may become limiting and be responsible for the age-related decline in protein synthesis. We have determined the expression levels of EF genes in Drosophila and have compared them with the expression of several other genes involved in the protein synthesis pathway. Steady-state levels of mRNAs for EF-1α F1 and F2, of mRNAs for four ribosomal proteins, of total poly A⁺ RNA, rRNA, and tRNA were measured. We show that most RNAs studied decrease immediately after eclosion. There is no evidence for EF-1α mRNA becoming limiting in old flies. Our data suggest that down-regulation of RNA polymerase I-, II-, and III-mediated transcription may contribute to an age-related decrease in protein synthesis or other homeostatic functions.

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“…The rate of protein synthesis appears to decline with age in many animal species (Lints & Bourgois, 1985;Moldave, 1985;Levenbook, 1986;Webster, 1986 -but see Finch, 1990). Experiments performed by Webster (1985) suggested that the age-related decline in protein synthesis in Drosophila might result from the decreased transcription of the EF-1o gene. The eukaryotic polypeptide chain elongation factor, EF-1c, is a GTP-binding protein that catalyses the binding of aminoacylated tRNAs to the ribosome (Riis et at., 1990).…”

Section: Introductionmentioning

confidence: 99%

P-element inserts in transgenic flies: a cautionary tale

Kaiser¹,

GASSER²,

ACKERMANN³

et al. 1997

Heredity

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The fruitfly, Drosophila melanogaster, can be transfected with P-elements and induced to overexpress a transfected gene whose impact on lifespan can be measured. Here, it is reported that in previous experiments a transfected gene was not expressed. This suggested a new statistical analysis indicating that (1) the size of the insert, the position and the interactions of the insert with the genetic backgrounds into which the P-element are inserted have effects on lifespan similar to those attributed to overexpression; (2) these effects occur without expression of the transfected gene; and (3) effects of interactions with backgrounds and effects of positions are as large as responses to six generations of strong directional artificial selection. Reports of effects of overexpression of transfected genes on lifespan in Drosophila melanogaster may be experimental artefacts. Credible experiments on the phenotypic effects of transgenesis need proper controls for the effects of insert size and position and should estimate the magnitudes of interactions of treatment with genetic backgrounds.

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Effect of Aging on the Components of the Protein Synthesis System

Cited by 15 publications

References 28 publications

Protein synthesis elongation factor EF-1 alpha expression and longevity in Drosophila melanogaster.

Protein synthesis elongation factor EF-1 alpha expression and longevity in Drosophila melanogaster.

Changes in the Expression of Genes Involved in Protein Synthesis during <i>Drosophil</i><i>a</i> Aging

P-element inserts in transgenic flies: a cautionary tale

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