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Michael R Rose

Publications and source records attributed to Michael R Rose.

At least 19 recordsLinked to original sources
PubMed2006

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.

Aging↗
PubMed2006

Do longevity mutants always show trade-offs?

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.

Aging↗
PubMed2006

Neurological disorders in Gulf War veterans.

We present a review of neurological function in Gulf War veterans (GWV). Twenty-two studies were reviewed, including large hospitalization and registry studies, large population-based epidemiological studies, investigations of a single military unit, small uncontrolled studies of ill veterans and small controlled studies of veterans. In nearly all studies, neurological function was normal in most GWVs, except for a small proportion who were diagnosed with compression neuropathies (carpal tunnel syndrome or ulnar neuropathy). In the great majority of controlled studies, there were no differences in the rates of neurological abnormalities in GWVs and controls. In a national US study, the incidence of amyotrophic lateral sclerosis (ALS) seems to be significantly increased in GWVs, compared to the rate in controls. However, it is possible that military service, in general, might be associated with an increased risk of ALS, rather than Gulf War service in particular. Taken together, the conclusion is that if a neurological examination in a GWV is within normal limits, then extensive neurological testing is unlikely to diagnose occult neurological disorders.

Gulf War↗
PubMed2006

A revolution for aging research.

In the year 1992, two publications on age-specific mortality rates revealed a cessation of demographic aging at later ages in very large cohorts of two dipteran species reared under a variety of conditions. Despite some initial concerns about possible artifacts, these findings have now been amply corroborated in the experimental literature. The eventual cessation of aging undermines the credibility of simple Gompertzian aging models based on a protracted acceleration in age-specific mortality during adulthood. The first attempt to explain the apparent cessation of aging was extreme lifelong heterogeneity among groups with respect to frailty. This lifelong heterogeneity theory assumes an underlying Gompertzian aging affecting every member of an adult cohort, with a merely apparent cessation of aging explained in terms of the increasing domination of a slowly aging group among the survivors to late ages. This theory has received several experimental refutations. The second attempt to explain the cessation of aging applied force of natural selection theory. This explanation of the cessation of aging has been corroborated in several Drosophila experiments. In particular, this theory requires that both age-specific survival and age-specific fecundity cease declining in late life, which has now been experimentally established. This theory also predicts that the timing of the cessation of aging should depend on the last age of reproduction in a population's evolutionary history, a prediction that has been corroborated. While lifelong heterogeneity should reduce average age-specific mortality in late life whenever it is pronounced, the cessation of aging in late life can be explained by plateaus in the forces of natural selection whether lifelong heterogeneity is present or not. The discovery that aging ceases is one of the most significant discoveries in recent aging research, with potentially revolutionary scientific implications.

Age Factors↗
PubMed2006

Caloric restriction increases longevity substantially only when the reaction norm is steep.

Evolutionary theory leads to the general expectation that dietary restriction will often result in increased survival probabilities, and thus increased lifespan. The reaction norm is a basic tool of evolutionary analysis that quantifies the relationship between environmental parameters and functional characters, including reproduction and longevity. In rodents, the reaction norm connecting adult longevity to caloric intake is fairly steep; small changes in intake lead to large changes in longevity. If this strong quantitative relationship were evolutionarily conserved among all mammals, then the prospects for a substantial increase in human lifespan from caloric restriction would be very good. In theory, however, reaction norms are expected to evolve for fitness related characters such as reproduction and survival. It has been shown experimentally in Drosophila that dietary reaction norms readily evolve in the laboratory, suggesting that they can do so among mammals as well, particularly over the millions of years since contemporary rodents and primates last shared a common ancestor. Our previous work crudely estimates that the dietary reaction norms of rodents and humans have diverged substantially, with a very flat dietary reaction norm for human longevity. These general principles and our specific results suggest that the benefits from human caloric restriction would be minor.

Adaptation, Physiological↗
PubMed2006

Rules for the use of model organisms in anti-aging pharmacology.

The use of animal models for initially screening anti-aging drugs is a promising approach for drug discovery. However, there a number of potential artifacts, confounds and errors that can arise in such research programs. The following rules are intended to minimize such problems: (1) since aging occupies an increasing proportion of human adulthood, data that conflate aging and late life should not be extrapolated to human aging; (2) the response to candidate medications should show a normal dose-response pattern, although not necessarily a linear response; (3) medicated animal models should not be hypometabolic; (4) medicated animal models should not show pronounced reductions in fertility; (5) medicated animal models should not exhibit general nervous system depression; (6) the effect of the medication should not be highly sensitive to the culture environment; (7) the effect of the medication should not be highly dependent on the genetic ancestry of the stock employed, leaving aside inbreeding, which should be avoided because humans are not generally inbred. While these rules do not guarantee successful extrapolation of successful drug results from the animal model to humans in a clinical setting, the failure to adhere to these rules should raise doubts about such extrapolation.

Aging↗
PubMed2006

The pharmacology of ageing in Drosophila.

Recent research indicates that aging is affected by many genes and thus many biochemical pathways. This has led to a failure to find pharmaceuticals that significantly ameliorate the human aging process. Progress in evolutionary and genetic research, however, suggests the possibility of combining experimental evolution, genomic analysis, and mass screening of pharmaceuticals and botanicals to produce effective therapeutics for human aging. The starting point for this strategy is model systems that have outbred populations with substantially increased lifespan. These are easily produced by tuning the force of natural selection in the laboratory. Such biological material is then a good candidate for genomic analysis, leading to the identification of numerous biochemical pathways involved in increased lifespan, in the model system. These biochemical pathways would then be available for pharmaceutical development, first in fruit flies, then in rodents, and eventually in a clinical human population. We include a discussion of the pharmacological methods appropriate to this strategy of drug discovery.

Aging↗
PubMed2005

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.

Aging↗
PubMed2005

The evolution of late life.

Late life is a distinct phase of life characterized by a cessation in the deterioration of survivorship and fecundity characteristic of normal aging. Several theories have been proposed to explain non-aging at late ages, specifically with regards to late-life mortality-rate plateaus. All such theories must be compatible with formal evolutionary theory and experimental findings. Here, we develop a critique of theories of late life based on evolutionary biology.

Age Factors↗
PubMed2005

Why dietary restriction substantially increases longevity in animal models but won't in humans.

Caloric restriction (CR) extends maximum longevity and slows aging in mice, rats, and numerous non-mammalian taxa. The apparent generality of the longevity-increasing effects of CR has prompted speculation that similar results could be obtained in humans. Longevity, however, is not a trait that exists in a vacuum; it evolves as part of a life history and the physiological mechanisms that determine longevity are undoubtedly complex. Longevity is intertwined with reproduction and there is a cost to reproduction. The impact of this cost on longevity can be age-independent or age-dependent. Given the complexity of the physiology underlying reproductive costs and other mechanisms affecting life history, it is difficult to construct a simple model for the relationship between the particulars of the physiology involved and patterns of mortality. Consequently, we develop a hypothesis-neutral model describing the relationship between diet and longevity. Applying this general model to the special case of human longevity and diet indicates that the benefits of caloric restriction in humans would be quantitatively small.

Age Factors↗
PubMed2005

Testing whether male age or high nutrition causes the cessation of reproductive aging in female Drosophila melanogaster populations.

Fecundity seems to stop declining and plateaus at low levels very late in Drosophila melanogaster populations. Here we test whether this apparent cessation of reproductive aging by a population, herein referred to as fecundity plateaus, is robust under various environmental influences: namely, male age and nutrition. The effect of male age on late age fecundity patterns was tested by supplying older females with young males before average population fecundity declined to plateau levels. The second possible environmental influence we tested was nutrition and whether late-life fecundity plateaus arise from a decline in the calories available for reproduction. This hypothesis was tested by comparing average daily female fecundity with both low- and high-lifetime nutrition. Both hypotheses were tested by measuring mid- and late-life fecundity for each cohort under the various environmental influences, and statistically testing whether fecundity stops declining and plateaus at late ages. These experiments demonstrate that mid- and late-life population fecundity patterns are significantly affected by the age of males and nutrition level. However, male age and nutrition level did not affect the existence of late-life fecundity plateaus, which demonstrates the robustness of our earlier findings. These results do not address any issue pertaining to the possible role, if any, of lifelong inter-individual heterogeneity in Drosophila fecundity.

Aging↗
PubMed2004

Quantitative genetics of functional characters in Drosophila melanogaster populations subjected to laboratory selection.

What are the genetics of phenotypes other than fitness, in outbred populations? To answer this question, the quantitative-genetic basis of divergence was characterized for outbred Drosophila melanogaster populations that had previously undergone selection to enhance characters related to fitness. Line-cross analysis using first-generation and second-generation hybrids from reciprocal crosses was conducted for two types of cross, each replicated fivefold. One type of cross was between representatives of the ancestral population, a set of five populations maintained for several hundred generations on a two-week discrete-generation life cycle and a set of five populations adapted to starvation stress. The other type of cross was between the same set of ancestral-representative populations and another set of five populations selected for accelerated development from egg to egg. Developmental time from egg to eclosion, starvation resistance, dry body weight and fecundity at day 14 from egg were fit to regression models estimating single-locus additive and dominant effects, maternal and paternal effects, and digenic additive and dominance epistatic effects. Additive genetic variation explained most of the differences between populations, with additive maternal and cytoplasmic effects also commonly found. Both within-locus and between-locus dominance effects were inferred in some cases, as well as one instance of additive epistasis. Some of these effects may have been caused by linkage disequilibrium. We conclude with a brief discussion concerning the relationship of the genetics of population differentiation to adaptation.

Animals↗
PubMed2004

Convergence to a novel environment: comparative method versus experimental evolution.

Laboratory adaptation allows researchers to contrast temporal studies of experimental evolution with comparative studies. The comparative method is here taken to mean the inference of microevolutionary processes from comparisons among contemporaneous populations of diverse origins, from one or multiple species. The data contrasted here come from Drosophila subobscura populations that were introduced to the laboratory at several different times and from two different locations. Two questions were addressed. First, can we correctly infer evolutionary dynamics from comparative data collected simultaneously from disparate populations? In most cases, we could, except for the character of starvation resistance. Second, are the evolutionary dynamics inferred from the comparative approach similar to those revealed by temporal studies of experimental evolution? For fecundity characters, they were. Overall the results show that both comparative and temporal studies are useful, though the former can be uninformative for characters with complex evolutionary trajectories.

Adaptation, Biological↗