Age-Dependent Changes in Proteins of
            <i>Drosophila melanogaster</i>

Fleming, James E.; Quattrocki, E; Latter, G; Miquel, Jaime; Marcuson, Richard; Zuckerkandl, Emile; Bensch, K.

doi:10.1126/science.3080809

Cited by 63 publications

(38 citation statements)

References 33 publications

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“…In essence, these theories can be divided into three broad categories: (i) those that predict posttranslational modifications such as protein crosslinkage (2) and deamidation or glycosylation (3); (ii) those that predict alterations in primary structure, such as the mutational theories (4-7) and the error-catastrophe hypothesis (8); and (iii) those that predict specific changes in the pattern or timing of protein expression, such as the genetic-program theories (9). Several investigations have demonstrated that posttranslational changes do indeed occur during senescence (10)(11)(12); however, unequivocal evidence showing an age-dependent effect on the fidelity of protein synthesis has not been reported (1,13). Previous studies in this laboratory gave no evidence that aged Drosophila express altered polypeptides (1).…”

mentioning

confidence: 64%

“…Many of the modern theories of molecular aging imply, directly or indirectly, that age-dependent changes occur in the molecular configuration or expression ofproteins and that these changes contribute to the diminution in the viability of senescent cells (1). In essence, these theories can be divided into three broad categories: (i) those that predict posttranslational modifications such as protein crosslinkage (2) and deamidation or glycosylation (3); (ii) those that predict alterations in primary structure, such as the mutational theories (4-7) and the error-catastrophe hypothesis (8); and (iii) those that predict specific changes in the pattern or timing of protein expression, such as the genetic-program theories (9).…”

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confidence: 99%

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Aging results in an unusual expression of Drosophila heat shock proteins.

Fleming¹,

Walton²,

Dubitsky³

et al. 1988

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

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We used high-resolution two-dimensional polyacrylamide gel electrophoresis to evaluate the effect of aging on the heat shock response in Drosophila melanogaster. Although the aging process is not well understood at the molecular level, recent observations suggest that quantitative changes in gene expression occur as these fruit flies approach senescence. Such genetic alterations are in accord with our present data, which clearly show marked differences in the synthesis of heat shock proteins between young and old fruit flies. In 10-day-old flies, a heat shock of 20 min results in the expression of 14 new proteins as detectable by two-dimensional electrophoresis of [35Slmethionine-labeled polypeptides, whereas identical treatment of 45-day-old flies leads to the expression of at least 50 new or highly up-regulated proteins. In addition, there is also a concomitant increase in the rate of synthesis of a number of the normal proteins in the older animals. Microdensitometric determinations of the low molecular weight heat shock polypeptides on autoradiographs of five age groups revealed that their maximum expression occurs at 47 days for a population of flies with a mean life span of 33.7 days. Moreover, a heat shock effect similar to that observed in senescent flies occurs in young flies fed canavanine, an arginine analogue, before heat shock.Many of the modern theories of molecular aging imply, directly or indirectly, that age-dependent changes occur in the molecular configuration or expression ofproteins and that these changes contribute to the diminution in the viability of senescent cells (1). In essence, these theories can be divided into three broad categories: (i) those that predict posttranslational modifications such as protein crosslinkage (2) and deamidation or glycosylation (3); (ii) those that predict alterations in primary structure, such as the mutational theories (4-7) and the error-catastrophe hypothesis (8); and (iii) those that predict specific changes in the pattern or timing of protein expression, such as the genetic-program theories (9). Several investigations have demonstrated that posttranslational changes do indeed occur during senescence (10-12); however, unequivocal evidence showing an age-dependent effect on the fidelity of protein synthesis has not been reported (1, 13). Previous studies in this laboratory gave no evidence that aged Drosophila express altered polypeptides (1). Two-dimensional gel electrophoresis data indicated that the qualitative pattern of protein expression was identical in young and old flies, but there were significant quantitative changes in the expression of proteins with age in the unstressed imago of Drosophila melanogaster.The expression of "new" polypeptides was also observed in non-heat-shocked senescent flies after exposure to inhibitors of mitochondrial function such as nonactin (14). These results suggest that qualitative changes in gene expression can be induced in aged animals by a metabolic or chemical stress. Thus, general perturbations of hom...

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mentioning

confidence: 64%

mentioning

confidence: 99%

Aging results in an unusual expression of Drosophila heat shock proteins.

Fleming¹,

Walton²,

Dubitsky³

et al. 1988

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

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“…Ten microliter samples (approximately 10 6 dpm) were applied under the electrolyte at the negative ends of the gels and then run at 500 V for 20 h. Each gel was loaded with the same amount of protein so as to minimize variation in spot migration due to protein loading, which is common for two-dimensional gel electrophoresis. The O populations took up slightly less label per milligram of protein than the B population, but relative spot intensity is adjusted by different exposure times of the film, as in Fleming et al (1986). All first dimension samples were run simultaneously in the same apparatus under identical conditions.…”

Section: Two-dimensional Gels and Radiolabellingmentioning

confidence: 99%

“…Gels were scored as previously described by Fleming et al (1986). The autoradiograph from population B 1 was arbitrarily chosen as the master gel.…”

Section: Two-dimensional Gels and Radiolabellingmentioning

confidence: 99%

Two-dimensional protein electrophoretic analysis of postponed aging in Drosophila

Fleming¹,

Spicer²,

Garrison³

et al. 1994

Genetics and Evolution of Aging

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Five populations of Drosophila melanogaster that had been selected for postponed aging were compared with five control populations using two-dimensional protein gel electrophoresis. The goals of the study were to identify specific proteins associated with postponed aging and to survey the population genetics of the response to selection. A total of 321 proteins were resolvable per population; these proteins were scored according to their intensity. The resulting data were analyzed using resampling, combinatoric, and maximum parsimony methods. The analysis indicated that the populations with postponed aging were different from their controls with respect to specific proteins and with respect to the variation between populations. The populations selected for postponed aging were more heterogeneous between populations than were the control populations. Maximum parsimony trees separate the selected populations, as a group, from their controls, thereby exhibiting a homoplastic pattern.

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“…Recent evidence indicates a genetic predisposition to perform at least some tasks within the colony (Calderone and Page, 1988;Frumhoff and Baker, 1988;Robinson andPage, 1988, 1989). Specificity of hormone activation in response to extrinsic stimuli appears to coordinate genotypic predispositions to task specialization (Jaycox, 1976;Jaycox et al, 1974 (Fleming et al, 1986). A new model is developing for age polyethism in workers which incorporates both genetic and epigenetic determinants for specific task performance (Robinson, 1987).…”

Section: Introductionmentioning

confidence: 99%