The fitness costs of senescence: The evolutionary importance of events in early adult life

Summary The increased mortality caused by ageing represents a fitness cost to organisms. This paper develops techniques for determining the proportions of that cost that accrue at each age. A variety of analyses using several different sources of data on human ageing—palaeodemographic life tables and life tables from more recent societies with high mortality rates—all suggest that the fitness cost of ageing was high during most of our evolutionary history, and was largely due to physiological changes occurring early in adult life. These results imply that predictions about the nature of senescence based on evolutionary theory should be tested using data from middle-aged individuals. They also have implications about the relative importances for human evolution of the pleiotropy and mutation-accumulation theories of the evolution of senescence, and for the validity of Gompertz Law' for the shape of the relationship between mortality and age. An analysis of a life table of the African buffalo suggests that the costs of ageing early in adult life are relatively high in at least one non-human species in its natural environment.     

The evolution of fidelity in sensory systems

We investigate the effect that noise has on the evolution of measurement strategies and competition in populations of organisms with sensory systems of differing fidelities. We address two questions motivated by experimental and theoretical work on sensory systems in noisy environments: (1) How complex must a sensory system be in order to face the need to develop adaptive measurement strategies that change depending on the noise level? (2) Does the principle of competitive exclusion for sensory systems force one population to win out over all others? We find that the answer to the first question is that even very simple sensory systems will need to change measurement strategies depending on the amount of noise in the environment. Interestingly, the answer to the second question is that, in general, at most two populations with different fidelity sensory systems may co-exist within a single environment.     

Ageing index evolution in the Spanish population

Official statistics allow an analysis of the ageing index changes in the Spanish population from 1930 to 1975. During this period the ageing index values doubled from 19.11 to 38.60, the maximum increase having occurred between 1950 and 1960. Both birth and death rates lowered during the 45 years studid; however, the death rate decreased twice as fast. The natural increase rise was thus mainly due to a lower death rate. These data can explain a part of the ageing index transformation. By province, the ageing index range increased three-fold from 1930 to 1975. Some provinces showed an elevated index and others a reduced one. After 1960, extensive areas of inland Spain showed an older age structure because of emigration to industrialized towns.     

The senescence of Daphnia from risky and safe habitats

Evaluating life history in an ecological context is critical for understanding the diversity of life histories found in nature. Lifespan and senescence differ greatly among taxa, but their ecological context is not well known. Life history theory proposes that senescence is ultimately caused by a reduction of the effectiveness of natural selection as organisms age. A key prediction is that different levels of extrinsic mortality risk lead to the evolution of different senescence patterns. I quantified both mortality risk and investment in late-life fitness of Daphnia pulex-pulicaria , a common freshwater zooplankter. I found that Daphnia from high-risk pond habitats invest relatively little in late-life fitness, whereas those from low-risk lake habitats invest relatively more in late-life fitness. This suggests that ecological approaches can be useful for understanding senescence variation.     

The case for negative senescence

Negative senescence is characterized by a decline in mortality with age after reproductive maturity, generally accompanied by an increase in fecundity. Hamilton (1966) ruled out negative senescence: we adumbrate the deficiencies of his model. We review empirical studies of various plants and some kinds of animals that may experience negative senescence and conclude that negative senescence may be widespread, especially in indeterminate-growth species for which size and fertility increase with age. We develop optimization models of life-history strategies that demonstrate that negative senescence is theoretically possible. More generally, our models contribute to understanding of the evolutionary and demographic forces that mold the age-trajectories of mortality, fertility and growth.     

Mating opportunity and the evolution of sex-specific mortality rates in a butterfly

Life history theory predicts that organisms should only invest resources into intrinsic components of life span to the degree that it pays off in terms of reproductive success. Here, we investigate if the temporal distribution of mating opportunities may have influenced the evolution of intrinsic mortality rates in the butterfly Pararge aegeria (Satyrinae). In this species, females mate only once and the frequency of male mating opportunities depends on the temporal emergence pattern of virgin females. As expected, in a population from Madeira where females emerge continuously throughout the year, there was no sex difference in adult life span, while in a Swedish population with synchronised female emergence, males had significantly shorter life spans compared to females. A logistic mortality model provided the best fit to the observed change in age-specific mortality and all categories reached an asymptotic mortality rate of a similar magnitude. However, the Swedish males reached this mortality plateau more rapidly than the other categories. External mortality, due to water and food limitation, affected the pattern of sex-specific mortality but males from Sweden still had higher rates of mortality compared to all other categories. We argue that selection on male longevity is likely to be weaker in Sweden because under synchronised emergence, all females emerge and mate within a short period of time, after which male reproductive value will quickly approach zero. On Madeira, however, male reproductive value decrease more slowly with age since the probability of finding a receptive female is constant over the year. Received: 29 July 1999 / Accepted: 23 August 1999     

Regime changes in ecological systems: an information theory approach

We present our efforts at developing an ecological system index using information theory. Specifically, we derive an expression for Fisher Information based on sampling of the system trajectory as it evolves in the space defined by the state variables of the system, i.e. its state space. The Fisher Information index, as we have derived it, is a measure of system order, and captures the characteristic variation in speed and acceleration along the system's periodic steady-state trajectories. When calculated repeatedly over the system period, this index tracks steady states and transient behavior. We believe that such an index could be useful in detecting system 'flips' associated with a regime change, i.e. determining when systems are in a transient between one steady state and another. We illustrate the concepts using model ecosystems.     

Complex systems, evolution, and animal models

In this paper, we respond to arguments made concerning our position regarding animal models (Shelley, 2010) by briefly examining the fact that animals (human and nonhuman) are complex systems that have different evolutionary trajectories. This historical fact has implications for using animals as predictive models for human response to drugs and disease.     

The evolution of premature reproductive senescence and menopause in human females

Reproductive senescence in human females takes place long before other body functions senesce. This fact presents an evolutionary dilemma since continued reproduction should generally be favored by natural selection. Two commonly proposed hypotheses to account for human menopause are (a) a recent increase in the human lifespan and (b) a switch to investment in close kin rather than direct reproduction. No support is found for the proposition that human lifespans have only recently increased. Data from Ache hunter-gatherers are used to test the kin selection hypothesis. Ache data do not support the proposition that females can gain greater fitness benefits in old age by helping kin rather than continuing to reproduce. Nevertheless, one crucial parameter in the model, when adjusted to the highest value within the measured 95% confidence interval, would lead to the evolution of reproductive senescence at about 53 years of age. Further investigation is necessary to determine whether the kin selection hypothesis of menopause can account for its current maintenance in most populations.     

Effect of cell senescence on the impedance measurement of adipose tissue-derived stem cells

Label-free and real-time monitoring of stem cells based on electrical impedance measurement is increasingly utilized for the quality control of the isolated stem cells to be used in stem cell-based tissue therapy or regenerative medicine. In spite of that the proliferative capacity and multipotency of stem cells are dependent on the type and age of the source tissue, however, the effect of the cell senescence on the impedance measurement of stem cells has not yet been studied. We investigated whether the senescence of adipose tissue-derived stem cells (ADSCs) can be detected by electrical impedance spectroscopy. For this, ADSCs at passage 9 and 31 were prepared and those genetic characteristics and growth kinetics were evaluated by quantitative polymerase chain reaction and cell counting. While the identified ADSCs were grown on the indium tin oxide electrodes, the impedance spectra were measured and interpreted by fitting analysis with an equivalent circuit model. ADSCs at passage 9 adhered on the electrode were small and spindle-shaped whereas the cells at passage 31 were flattened and larger than younger cells. At the beginning of culture time when the cell adhesion occurred, the resistance at 4.6 kHz of passage 31 cells was higher than passage 9 due to the larger size of older cells. Afterwards, the value of passage 9 cells increased higher than passage 31, since younger cells proliferated more than old cells. Therefore, the impedance measurement could characterize the proliferative capacity of ADSCs during expanded culture.     

The evolution of senescence and post-reproductive lifespan in guppies (Poecilia reticulata)

The study of post-reproductive lifespan has been of interest primarily with regard to the extended post-menopausal lifespan seen in humans. This unusual feature of human demography has been hypothesized to have evolved because of the “grandmother” effect, or the contributions that post-reproductive females make to the fitness of their children and grandchildren. While some correlative analyses of human populations support this hypothesis, few formal, experimental studies have addressed the evolution of post-reproductive lifespan. As part of an ongoing study of life history evolution in guppies, we compared lifespans of individual guppies derived from populations that differ in their extrinsic mortality rates. Some of these populations co-occur with predators that increase mortality rate, whereas other nearby populations above barrier waterfalls are relatively free from predation. Theory predicts that such differences in extrinsic mortality will select for differences in the age at maturity, allocation of resources to reproduction, and patterns of senescence, including reproductive declines. As part of our evaluation of these predictions, we quantified differences among populations in post-reproductive lifespan. We present here the first formal, comparative study of the evolution of post-reproductive lifespan as a component of the evolution of the entire life history.

Guppies that evolved with predators and that experienced high extrinsic mortality mature at an earlier age but also have longer lifespans. We divided the lifespan into three non-overlapping components: birth to age at first reproduction, age at first reproduction to age at last reproduction (reproductive lifespan), and age at last reproduction to age at death (post-reproductive lifespan). Guppies from high-predation environments live longer because they have a longer reproductive lifespan, which is the component of the life history that can make a direct contribution to individual fitness. We found no differences among populations in post-reproductive lifespan, which is as predicted since there can be no contribution of this segment of the life history to an individual's fitness.

Prior work on the evolution of post-reproductive lifespan has been dominated by speculation and correlative analyses. We show here that this component of the life history is accessible to formal study as part of experiments that quantify the different segments of an individual's life history. Populations of guppies subject to different mortality pressures from predation evolved differences in total lifespan, but not in post-reproductive lifespan. Rather than showing the direct effects of selection characterizing other life-history traits, post-reproductive lifespan in these fish appears to be a random add-on at the end of the life history. These findings support the hypothesis that differences in lifespan evolving in response to selection are confined to the reproductive lifespan, or those segments of the life history that make a direct contribution to fitness. We also show, for the first time, that fish can have reproductive senescence and extended post-reproductive lifespans despite the general observation that they are capable of producing new primary oocytes throughout their lives.

     

Birth-and-death evolution of protein-coding regions and concerted evolution of non-coding regions in the multi-component genomes of nanoviruses

Genomes of the four plant viruses of the genus Nanovirus consist of multiple circular single-stranded DNA components, each of which encodes a single protein. Protein phylogenies supported the hypothesis that faba bean necrotic yellows virus (FBNYV) and milk vetch disease virus (MDV) are sister taxa; that subterranean clover stunt virus (SCSV) branched next; and that banana bunchy top virus (BBTV) is an outgroup to the three other species. The phylogeny of replication (Rep) proteins indicate that this small viral multi-gene family has evolved by a process of duplication and subsequent loss of Rep-encoding genome components, analogous to the "birth-and-death" process of evolution which has been described in eukaryotic multi-gene families. By contrast, repeated recombinational events between components were found to have homogenized the non-coding portions of several components encoding unrelated components. For example, as result of recent recombination a portion of the non-coding region is virtually identical among SCSV components 1, 3, 4, 5, and 7. Thus, there is a process of concerted evolution of non-coding regions of Nanovirus genome components, which raises the possibility that certain non-coding regions are subject to functional constraint.     

The evolution of adaptive immune systems

A clonally diverse anticipatory repertoire in which each lymphocyte bears a unique antigen receptor is the central feature of the adaptive immune system that evolved in our vertebrate ancestors. The survival advantage gained through adding this type of adaptive immune system to a pre-existing innate immune system led to the evolution of alternative ways for lymphocytes to generate diverse antigen receptors for use in recognizing and repelling pathogen invaders. All jawed vertebrates assemble their antigen-receptor genes through recombinatorial rearrangement of different immunoglobulin or T cell receptor gene segments. The surviving jawless vertebrates, lampreys and hagfish, instead solved the receptor diversification problem by the recombinatorial assembly of leucine-rich-repeat genetic modules to encode variable lymphocyte receptors. The convergent evolution of these remarkably different adaptive immune systems involved innovative genetic modification of innate-immune-system components.     

Sexual selection effects on the evolution of senescence

Although the basic theories concerning evolution of senescence have been generally accepted for a half-century, interpretation of this paradigm has been constrained by an over-reliance on mortality as both the cause and the measure of senescence. Consideration of both survival and fecundity as components of reproductive value, and integration of sexual selection theory with senescence theory allows reconciliation of long-standing, as well as recent, discrepancies between data and theory. This approach demonstrates that sexual selection on males in polygynous mating systems can have significant effects on the evolution of senescence that could overshadow the selection effects of mortality rates among such animals.     

The use of transgenic systems in pharmaceutical research.

Those pharmaceutical companies whose goal is to generate novel innovative drugs are faced with the challenge that only a fraction of the compounds tested in clinical trials eventually become a registered drug. This problem of attrition is compounded by the fact that the clinical trial or development stage is by far the most costly phase of bringing a new drug to market, consuming around 80 per cent of the total spend. Transgenic technology represents an attractive approach to reducing the attrition rate of compounds entering clinical trials by increasing the quality of the target and compound combinations making the transition from discovery into development. Transgenic technology can impact at many points in the discovery process, including target identification and target validation, and provides models designed to alert researchers early to potential problems with drug metabolism and toxicity, as well as providing better models for human diseases. In target identification, transgenic animals harbouring large DNA fragments can be used to narrow down genetic regions. Genetic studies often result in the identification of large genomic regions and one way to decrease the region size is to do complementation studies in transgenic animals using, for example, inserts from bacterial artificial chromosome (BAC) clones. In target validation, transgenic animals can be used for in vivo validation of a specific target. Considerable efforts are being made to establish new, rapid and robust tools with general utility for in vivo validation, but, so far, only transgenic animals work reliably on a wide range of targets. Transgenic animals can also be used to generate better disease models. Predictive animal models to test new compounds and targets will significantly speed up the drug discovery process and, more importantly, increase the quality of the compounds taken further in the research and development process. Humanised transgenic animals harbouring the human target molecule can be used to understand the effect of a compound acting on the human target in vivo. Also, models mimicking human drug metabolism will provide a means of assessing the effect of human-specific metabolites and of understanding the pharmacokinetic properties of potential drugs. In toxicology studies, transgenic animals are providing more predictive models. A good example of this are those models routinely used to look for carcinogenicity associated with new compounds.