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T J Nusbaum

Publications and source records attributed to T J Nusbaum.

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The effects of nutritional manipulation and laboratory selection on lifespan in Drosophila melanogaster.

There are parallels between the effects of laboratory selection and nutritional manipulation on the expression of lifespan and other fitness-related characters in Drosophila melanogaster. However, little is known about the effects of laboratory selection and nutritional manipulation when applied simultaneously. Given that D. melanogaster is one of the major model organisms for testing theories of aging, simultaneous application of laboratory selection and nutritional manipulation is of considerable interest. To that end we developed six groups of five fold replicated populations selected for either early or late fertility. Each of these groups was maintained on either high- or low-nutrition diets. Comparisons among the groups showed that nutrition is neutral in selecting for lifespan. Moreover, the dietary-restriction response can be broken by simultaneous selection and nutritional manipulation. Finally, characters that respond in a parallel manner under selection or nutritional manipulation may not when the two are applied simultaneously.

Animal Nutritional Physiological Phenomena↗

Prospects for postponing human aging.

The postponement of human aging is a long-standing aspiration in many cultures, particularly non-Western ones. Renewed interest in this goal is now being shown within the biomedical research context. This interest has probably arisen because several different approaches have yielded dramatic increases in mean and maximum life span in laboratory organisms. Among the cases where aging has been postponed in animal models are the nematode, Caenorhabditis elegans, the common lab fruit fly, Drosophila melanogaster, and the dietarily restricted rodent, both Mus and Rattus. These successes raise the question of whether similar postponement of aging might be achieved in humans. Among the broad research strategies available, five can be delineated: 1) random testing of favorite interventions; 2) searching for genes that can postpone aging among all or most species; 3) study of in vitro mammalian cell cultures; 4) study of dietarily restricted mammals; and 5) selecting mammals for postponed aging. Although all these methods could conceivably lead to the postponement of human aging, they are very different from each other with respect to their degree of uncertainty, cost, and delay.

Aging↗

Drosophila with postponed aging as a model for aging research.

Species of the genus Drosophila, commonly known as "fruitflies," are good model systems for research in aging. Drosophila are extremely well-known genetically, developmentally, and otherwise. They are also genetically analogous to mammalian species in most important respects. Previous work with Drosophila has been hampered by inbreeding depression, but more recent work using selection has created Drosophila with postponed aging that is inherited normally. Genetic transformation has also increased Drosophila life spans in some cases. Several biologic approaches have been applied to the analysis of genetically postponed aging in Drosophila: quantitative genetics, organismal physiology, and protein electrophoresis. Ultimately, these different approaches will be integrated into an overall analysis of aging in Drosophila, one that could be valuable for research with other taxa as well.

Aging↗

The Gompertz equation as a predictive tool in demography.

The Gompertz demographic model describes rates of aging and age-independent mortality with the parameters alpha and A, respectively. Estimates of these parameters have traditionally been based on the assumption that mortality rates are constant over short to moderate time periods. This assumption is questionable even for very large samples assayed over short time intervals. In this article, we compare several methods for estimating the Gompertz parameters, including some that do not assume constant mortality rates. A maximum likelihood method that does not assume constant mortality rates is shown to be best, based on the bias and variance of the Gompertz parameter estimates. Moreover, we show how the Gompertz equation can then be used to predict mean longevity and the time of the nth percentile of mortality. Methods are also developed that assign confidence intervals to such estimates. In some cases, these statistics may be estimated accurately from only the early deaths of a large cohort, thus providing an opportunity to estimate longevity on long-lived organisms quickly.

Computer Simulation↗

Evolutionary patterns among measures of aging.

Maximum lifespan has been one of the most common aging measures in comparative studies, while the Gompertz model has recently attracted both proponents and critics of its capacity to adequately describe the acceleration of mortality in the oldest age classes. The Gompertz demographic model describes age-dependent mortality rate acceleration and age-independent mortality using the parameters alpha and A, respectively. Evolutionary biologists have predominantly used average longevity in studies of aging. Little is known about the evolutionary relationships of these measures on the microevolutionary time scale. We have simultaneously compared Gompertz parameters, average longevity, and maximum longevity in 50 related populations of Drosophila melanogaster, many of which have been selected for postponed aging. Overall, these populations have differentiated significantly for the A and alpha parameter of the Gompertz equation, as well as average and maximum longevity. These indices of aging appear to measure the same genetic changes in aging. However, in some specific population comparisons, the relationships among these measures are more complex. In a second experiment, environmental manipulation of longevity had substantially different effects from genetic differentiation, with the A parameter accounting for changes in overall mortality. The adequacy of the maximum lifespan and the Gompertz equation as indices of aging in evolutionary studies is discussed.

Aging↗