Casandra L. Rauser

EVOLUTION OF LATE-LIFE MORTALITY IN DROSOPHILA MELANOGASTER

Abstract.— Aging appears to cease at late ages, when mortality rates roughly plateau in large‐scale demographic studies. This anomalous plateau in late‐life mortality has been explained theoretically in two ways: (1) as a strictly demographic result of heterogeneity in life‐long robustness between individuals within cohorts, and (2) as an evolutionary result of the plateau in the force of natural selection after the end of reproduction. Here we test the latter theory using cohorts of Drosophila melanogaster cultured with different ages of reproduction for many generations. We show in two independent comparisons that populations that evolve with early truncation of reproduction exhibit earlier onset of mortality‐rate plateaus, in conformity with evolutionary theory. In addition, we test two population genetic mechanisms that may be involved in the evolution of late‐life mortality: mutation accumulation and antagonistic pleiotropy. We test mutation accumulation by crossing genetically divergent, yet demographically identical, populations, testing for hybrid vigor between the hybrid and nonhybrid parental populations. We found no difference between the hybrid and nonhybrid populations in late‐life mortality rates, a result that does not support mutation accumulation as a genetic mechanism for late‐life mortality, assuming mutations act recessively. Finally, we test antagonistic pleiotropy by returning replicate populations to a much earlier age of last reproduction for a short evolutionary time, testing for a rapid indirect response of late‐life mortality rates. The positive results from this test support antagonistic pleiotropy as a genetic mechanism for the evolution of late‐life mortality. Together these experiments comprise the first corroborations of the evolutionary theory of late‐life mortality.

Hamilton's forces of natural selection after forty years

Abstract In 1966, William D. Hamilton published a landmark paper in evolutionary biology: “The Moulding of Senescence by Natural Selection.” It is now apparent that this article is as important as his better-known 1964 articles on kin selection. Not only did the 1966 article explain aging, it also supplied the basic scaling forces for natural selection over the entire life history. Like the Lorentz transformations of relativistic physics, Hamiltons Forces of Natural Selection provide an overarching framework for understanding the power of natural selection at early ages, the existence of aging, the timing of aging, the cessation of aging, and the timing of the cessation of aging. His twin Forces show that natural selection shapes survival and fecundity in different ways, so their evolution can be somewhat distinct. Hamiltons Forces also define the context in which genetic variation is shaped. The Forces of Natural Selection are readily manipulable using experimental evolution, allowing the deceleration or acceleration of aging, and the shifting of the transition ages between development, aging, and late life. For these reasons, evolutionary research on the demographic features of life history should be referred to as “Hamiltonian.”

Evolution of late-life fecundity in Drosophila melanogaster

Late‐life fecundity has been shown to plateau at late ages in Drosophila analogously to late‐life mortality rates. In this study, we test an evolutionary theory of late life based on the declining force of natural selection that can explain the occurrence of these late‐life plateaus in Drosophila. We also examine the viability of eggs laid by late‐age females and test a population genetic mechanism that may be involved in the evolution of late‐life fecundity: antagonistic pleiotropy. Together these experiments demonstrate that (i) fecundity plateaus at late ages, (ii) plateaus evolve according to the age at which the force of natural selection acting on fecundity reaches zero, (iii) eggs laid by females in late life are viable and (iv) antagonistic pleiotropy is involved in the evolution of late‐life fecundity. This study further supports the evolutionary theory of late life based on the age‐specific force of natural selection.

Aging, fertility, and immortality

Evolutionary theory suggests that fecundity rates will plateau late in life in the same fashion as mortality rates. We demonstrate that late-life plateaus arise for fecundity in Drosophila melanogaster. The result qualitatively fits the evolutionary theory of late life based on the force of natural selection. But there are a number of alternative interpretations. Fecundity plateaus could be secondary consequences of mortality-rate plateaus. Female fecundity plateaus might arise from diminished male sexual function. Another alternative hypothesis is analogous to male sexual inadequacy: nutritional shortfalls. These may arise later in life because of a decline in female feeding or digestion. If some females have a life-long tendency to lay eggs at a faster rate, but die earlier, then aging for fecundity could arise from the progressive loss of the fast-layers, with the late-life plateau simply the laying patterns of individual females who were slow-layers throughout adult life. If this type of model is generally applicable to late life, then we should find that the females who survive to lay at a slow but steady rate in late life have a similar laying pattern in mid-life.

Lifelong heterogeneity in fecundity is insufficient to explain late-life fecundity plateaus in Drosophila melanogaster

Previous studies have demonstrated that fecundity, like mortality, plateaus at late ages in cohorts of Drosophila melanogaster. Although evolutionary theory can explain the decline and plateau in cohort fecundity at late ages, it is conceivable that lifelong heterogeneity in individual female fecundity is producing these plateaus. For example, consistently more fecund females may die at earlier ages, leaving only females that always laid a low number of eggs preponderant at later ages. We simulated fecundity within a cohort, assuming the two phenotypes described above, and tested these predictions by measuring age of death and age-specific fecundity for individual females from three large cohorts. We statistically tested whether there was enough lifelong heterogeneity in fecundity to produce a late-life plateau by testing whether early female fecundity could predict whether that female would live to lay eggs after the onset of the population fecundity plateau. Our results indicate that heterogeneity in fecundity is not lifelong and thus not likely to cause late-life fecundity plateaus. Because lifelong heterogeneity models for fecundity are based on the same underlying assumptions as heterogeneity models for late-life mortality rates, our test of this hypothesis is also an experimental test of lifelong heterogeneity models of late life generally.

An evolutionary heterogeneity model of late-life fecundity in Drosophila

There is now a significant body of research that establishes the deceleration of mortality rates in late life and their ultimate leveling off on a late-life plateau. Natural selection has been offered as one mechanism responsible for these plateaus. The force of natural selection should also exert such effects on female fecundity. We have already developed a model of female fecundity in late life that incorporates the general predictions of the evolutionary model. The original evolutionary model predicts a decline in fecundity from a peak in early life, followed by a plateau with non-zero fecundity in late life. However, in Drosophila there is also a well-defined decline in fecundity among dying flies, here called the “death spiral”. This effect produces heterogeneity between dying and non-dying flies. Here a hybrid evolutionary heterogeneity model is developed to accommodate both the evolutionary plateau prediction and the death spiral. It is shown that this evolutionary heterogeneity model gives a much better fit to late-life fecundity data.

Interactions between injury, stress resistance, reproduction, and aging in Drosophila melanogaster

An important aspect of the aging process in Drosophila melanogaster is the natural loss of antennae, legs, bristles, and parts of wings with age. These injuries lead to a loss of hemolymph, which contains water and nutrients. Stress-resistant lines of D. melanogaster are sometimes longer-lived than the populations from which they are derived. One hypothesis tested here is that increased stress-resistance fosters longevity because it allows fruit flies to cope with the loss of hemolymph due to injury to the aging fly. We tested the effects of surgically induced injury on the aging and reproduction of five replicate populations. We then tested the effects of injury on populations that had been selected for different levels of stress resistance and on control populations. Injury affected aging more in males than in females, in part because of a counter-balancing reduction in female reproduction brought about by injury. More specifically, injury reduced female fecundity and male virility. Injury significantly reduced the starvation resistance in some groups of flies, but not in others. These findings undermine any simple interpretation of the interactions between injury, reproduction, and aging based on stress resistance. But they do indicate the existence of significant interactions between these biological processes, interactions that should be resolved in greater mechanistic detail than has been managed here.

Late Life: A New Frontier for Physiology

Late life is a distinct phase of life that occurs after the aging period and is now known to be general among aging organisms. While aging is characterized by a deterioration in survivorship and fertility, late life is characterized by the cessation of such age‐related deterioration. Thus, late life presents a new and interesting area of research not only for evolutionary biology but also for physiology. In this article, we present the theoretical and experimental background to late life, as developed by evolutionary biologists and demographers. We discuss the discovery of late life and the two main theories developed to explain this phase of life: lifelong demographic heterogeneity theory and evolutionary theory based on the force of natural selection. Finally, we suggest topics for future physiological research on late life.

Predicting death in female Drosophila

We have previously described a phenomenon called the death spiral that is characterized by a rapid decline in female fecundity 6-15 days prior to death in Drosophila. To carry out destructive physiological analyses of females in the death spiral would require a method to reliably classify individual females via the prediction of their age at death. Using cohorts of Drosophila we describe how to use the observed mortality prior to some target day and a females fecundity 3 days prior to the target day to determine if the female is in the death spiral. The method works at all ages and although the method does not result in perfect classification, with sufficient sample sizes any physiological trait whose means differ between the groups can be detected.

Population Dynamics, Life History, and Demography: Lessons From Drosophila

Publisher Summary This chapter reviews the important lessons in ecology and life history evolution that have been learned from studies of laboratory populations of Drosophila. The use of experimental systems of Drosophila has contributed to the understanding of density-dependent and age-specific natural selection and population dynamics. Laboratory experiments have repeatedly allowed testing of the general theories of ecology. The great strength of laboratory experimental systems is their power when testing a theory. These experimental populations are maintained in a way that eliminates confounding factors that are present in field systems. The complications of natural populations, like heterogeneous environments, migration, meteorological disaster, and so on, should not be viewed as barriers to laboratory studies but as challenges. There is still very little experimental work on the population dynamics of age-structured populations. It is unclear how age-structure affects population stability.