Publications by authors named "James W Curtsinger"

There are two life history landmarks that can be used to define the terminal period in individual Drosophila melanogaster females: the cessation of daily oviposition, which defines the start of the retired stage, and final oviposition, which defines the start of post-ovipository survival. The terminal period is a substantial component of D. melanogaster life history.

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Artificial selection for increased life span in experimental populations of Drosophila melanogaster sometimes produces long-lived populations that exhibit greater fecundity than unselected controls. The absence of a trade-off between survival and reproduction in these cases might be an artefact of the rich diet of typical lab culture; if nutritional resources are not limiting then there may be no need to trade off. Here I test the rich diet hypothesis by estimating genetic correlations between survival and age-specific fecundity in three nutritional environments.

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The homeostatic properties of reproduction in aging female Drosophila melanogaster are investigated. Classic studies based on cohort analysis suggest that homeostatic capacity declines gradually as daily oviposition rates decline in aging flies. Analysis at the level of individuals gives a very different picture: reproductive homeostasis remains relatively constant for most of adult life until a critical point when oviposition either ceases entirely or continues in dysregulated fashion.

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Late-life plateaus in age-specific mortality have been an evolutionary and biodemographic puzzle for decades. Although classic theory on the evolution of senescence predicts late-life walls of death, observations in experimental organisms document the opposite trend: a slowing in the rate of increase of mortality at advanced ages. Here, I analyze published life-history data on individual Drosophila melanogaster females and argue for a fundamental change in our understanding of mortality in this important model system.

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Life history observations at the level of individual model organisms are relatively scarce, but highly informative. Here I analyze published data on the survival and lifetime fecundity of 3,971 individually housed, mated Drosophila melanogaster females from nine experimental populations. Data were collected from four laboratories and include counts of over 4.

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Late-life plateaus have been described in both cohort and individual trajectories of fecundity in Drosophila melanogaster females. Here I examine life history data recently analyzed by Le Bourg and Moreau (2014) and show that non-linearity in the cohort trajectory of fecundity is largely explained by heterogeneity in the duration of reproductive life spans. A model specifying linear post-peak decline of fecundity in individual flies provides a better fit to the data than one that combines linear decline with late-life fecundity plateaus.

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Population trajectories of age-specific fecundity in Drosophila melanogaster typically decline with increasing age and then exhibit an upward inflection, or "plateau", at the oldest ages. This pattern has been interpreted as evidence of an evolved and physiologically distinct life history stage in late life. While low levels of fecundity are common in the last few days of life of individual flies, it is unclear that defining a single age as the beginning of a period of low fecundity for the entire cohort is useful, since reproductive life spans vary substantially from fly to fly.

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Populations of Drosophila melanogaster that have been artificially selected for late age of reproduction evolve longer life spans and, in some cases, reduced early fecundity. The negative correlation is widely interpreted as evidence of antagonistic pleiotropy. Here, we show that the correlation breaks down in recombinant genomes.

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We measured age-specific fecundity and survival in recombinant inbred lines of Drosophila melanogaster that were derived from an artificial selection experiment for delayed reproduction. Age at peak oviposition is highly heritable (h(2) (B) = 0.55).

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Our current understanding of the genetics of aging stems largely from 2 decades of research involving animal models. The research is yielding evidence that aging is a complicated process involving multiple genes and their interactions. It is also showing that aging and life span can be manipulated.

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Genetic variation in adult life span, resistance to paraquat, resistance to DDT, and spontaneous flying activity were measured in 138 recombinant inbred lines of Drosophila melanogaster. We find that the phenotypic correlation between life span and resistance to an exogenous oxidizing agent is positive, though weak, and that there is little correlation between the two traits at the level of quantitative trait loci (QTLs). The sign of the life span-resistance correlation is haplotype-specific, suggesting a high degree of statistical interaction and dependence on genetic background.

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A number of genetic mutations that substantially increase longevity have been discovered in model organisms. Although these long-lived mutants have provided many insights into the factors that affect longevity, the results from such studies should be interpreted with caution. In particular, at least some of these mutations may be poor guides to human medical intervention because they often have deleterious side effects on important biological functions.

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Among mammals, body size and life span tend to vary inversely within species, but the pattern is less clear in invertebrates. Here, we report on survival and weight of male flies from 29 laboratory strains of Drosophila melanogaster. Natural variation in body mass was enhanced by rearing larvae under normal and limited food conditions.

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We used quantitative trait loci (QTL) mapping to evaluate the age specificity of naturally segregating alleles affecting life span. Estimates of age-specific mortality rates were obtained from observing 51,778 mated males and females from a panel of 144 recombinant inbred lines (RILs). Twenty-five QTL were found, having 80 significant effects on life span and weekly mortality rates.

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We investigated the correlation between age and total RNA levels in long-lived and control lines of Drosophila melanogaster. Total RNA was extracted at 10 ages from 1-63 days posteclosion from 3 inbred lines, with replication. Three different methods of RNA quantitation gave highly correlated estimates.

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We measured age-specific metabolic rates in 2861 individual Drosophila melanogaster adult males to determine how genetic variation in metabolism is related to life span. Using recombinant inbred (RI) lines derived from populations artificially selected for long life, resting metabolic rates were measured at 5, 16, 29, and 47 days posteclosion, while life spans were measured in the same genotypes in mixed-sex population cages and in single-sex vials. We observed much heritable variation between lines in age-specific metabolic rates, evidence for genotype x age interaction, and moderate to large heritabilities at all ages except the youngest.

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In a recent study examining the relationship between longevity and metabolism in a large number of recombinant inbred Drosophila melanogaster lines, we found no indication of the inverse relationship between longevity and metabolic rate that one would expect under the classical "rate of living" model. A potential limitation in generalizing from that study is that it was conducted on experimental material derived from a single set of parental strains originally developed over 20 years ago. To determine whether the observations made with those lines are characteristic of the species, we studied metabolic rates and longevities in a second, independently derived set of recombinant inbred lines.

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An approach towards analyzing survivorship data is proposed for the study of changes in stress resistance with age in the population of Drosophila melanogaster. This is based on the model of heterogeneous mortality (frailty model). Results of the data analysis show that observed populations of flies are heterogeneous and the accelerated selection, debilitative effect and changes in individual frailties are the aftermath of stress.

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We examined the association between body mass and metabolic rate in Drosophila melanogaster under a variety of conditions. These included comparisons of body mass and metabolic rate in flies from different laboratory lines measured at different ages, over different metabolic sampling periods, and comparisons using wet versus dry mass data. In addition, the relationship between body mass and metabolic rate was determined for flies recently collected from wild populations.

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The use of model organisms, such as Drosophila melanogaster, provides a powerful method for studying mechanisms of aging. Here we report on a large set of recombinant inbred (RI) D. melanogaster lines that exhibit approximately a fivefold range of average adult longevities.

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Most of the quantitative trait loci (QTLs) that have been found to influence life span in Drosophila and Mus organisms are reported to have genetic effects limited to one sex. Here I study the statistical properties of sex-limited QTLs by randomly sampling data from an exceptionally large Drosophila experiment, and then asking how sample size influences outcomes. The sampling study suggests that, for the particular data analyzed here, even moderately large experiments, of the order of 10(4) individuals, can have a high probability of detecting sex-limited effects when they are not actually present.

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We have constructed a set of 120 recombinant inbred lines for use in studies of the genetics of lifespan in Drosophila. The lines are derived from Luckinbill and Clare's (Heredity 55 (1985) 9) artificial selection experiment for increased lifespan. Inbred lines retain the relative lifespan characteristics of the experimental and control stocks from which they are derived.

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Age-specific mortality rates level off far below 100% at advanced ages in experimental populations of Drosophila melanogaster and other organisms. This observation is inconsistent with the equilibrium predictions of both the antagonistic pleiotropy and mutation accumulation models of senescence, which, under a wide variety of assumptions, predict a "wall" of mortality rates near 100% at postreproductive ages. Previous models of age-specific mortality patterns are discussed in light of recent demographic data concerning late-age mortality deceleration and age-specific properties of new mutations.

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