The influence of the medical care on the human life expectancy in 20th century and the Penna ageing model

Summary The expression of many genetic defects may be suppressed by proper medical care or even by changing the environmental conditions. We have used the Penna model of ageing to show that such efFects may be responsible for increasing the human life expectancy during the 20 ^th century. This effect is equivalent to the shift of the threshold (T) in the Penna model, which determines how many deleterious, expressed mutations kill an organism. For long genomes, the shift of T changes the age distribution significantly with negligible relative changes in the maximum life span, while for short genomes, the shift of T changes both, the age distribution as well as the maximum age. Unfortunately the same simulations show that the strategy of enhancing the medical care requires more and more effort to keep the mortality rate of our populations at the same lower level and that some new defects could be exposed to selection.     

Catastrophic senescence and semelparity in the Penna aging model

The catastrophic senescence of the Pacific salmon is among the initial tests used to validate the Penna aging model. Based on the mutation accumulation theory, the sudden decrease in fitness following reproduction may be solely attributed to the semelparity of the species. In this work, we report other consequences of mutation accumulation. Contrary to earlier findings, such dramatic manifestation of aging depends not only on the choice of breeding strategy but also on the value of the reproduction age, R, and the mutation threshold, T. Senescence is catastrophic when T ￡ R.T \le R. As the organism’s tolerance for harmful genetic mutations increases, the aging process becomes more gradual. We observe senescence that is threshold dependent whenever T > R. That is, the sudden drop in survival rate occurs at age equal to the mutation threshold value.     

The risk of extinction—the mutational meltdown or the overpopulation

The phase diagrams survival-extinction for the Penna model with parameters: (mutations rate)-(birth rate), (mutation rate)-(harmful mutations threshold), (harmful mutation threshold)-(minimal reproduction age) are presented. The extinction phase may be caused by either mutational meltdown or overpopulation. When the Verhulst factor is responsible for removing only newly born babies and does not act on adults the overpopulation is avoided and only genetic factors may lead to species extinction.     

Stability of the analytical solution of Penna model of biological aging

There are some analytical solutions of the Penna model of biological aging; here, we discuss the approach by Coe et al. (Phys. Rev. Lett. 89, 288103, 2002), based on the concept of self-consistent solution of a master equation representing the Penna model. The equation describes transition of the population distribution at time t to next time step (t + 1). For the steady state, the population n(a, l, t) at age a and for given genome length l becomes time-independent. In this paper we discuss the stability of the analytical solution at various ranges of the model parameters—the birth rate b or mutation rate m. The map for the transition from n(a, l, t) to the next time step population distribution n(a + 1, l, t + 1) is constructed. Then the fix point (the steady state solution) brings recovery of Coe et al. results. From the analysis of the stability matrix, the Lyapunov coefficients, indicative of the stability of the solutions, are extracted. The results lead to phase diagram of the stable solutions in the space of model parameters (b, m, h), where h is the hunt rate. With increasing birth rate b, we observe critical b ₀ below which population is extinct, followed by non-zero stable single solution. Further increase in b leads to typical series of bifurcations with the cycle doubling until the chaos is reached at some b _c. Limiting cases such as those leading to the logistic model are also discussed.     

Influence of previous agonistic interactions with conspecifics on contest decisions

Recent wins and losses can inform individuals about their relative fighting abilities and modify their subsequent contest decisions. Using a mangrove rivulus, Kryptolebias marmoratus, we tested the hypothesis that visual and limited physical interactions can also convey information and modify subsequent contest decisions. Individuals were exposed to a stronger or weaker conspecific through a glass or a mesh partition before a contest with a size‐matched naïve opponent. Individuals were expected to (a) assess themselves to have worse/better fighting ability and behave less/more aggressively after having interacted with a stronger/weaker conspecific and (b) display different degrees of behavioural modifications for the two partition treatments (mesh‐partition > glass‐partition). The results showed that interactions with a stronger/weaker conspecific through a glass partition did not have a strong effect on the fish's subsequent contest behaviour. Restricted physical interaction with a stronger/weaker conspecific through a mesh partition, however, had an unexpected effect, causing individuals to behave more/less aggressively (matching the behaviour of the conspecifics) and/or win more/fewer subsequent contests. These results indicate that contest resolution is important for the fish to exhibit the loser–winner effects (i.e. behaving less/more aggressively after having lost/won against a stronger/weaker conspecific) detected in previous studies of the fish. We propose and discuss the possibility that the “behavioural matching” of the mesh‐partition treatment results from unresolved physical interactions with a stronger/weaker conspecific causing the individuals to either anticipate stronger/weaker opponents in subsequent competitions or assess themselves to be an equally good/bad fighter as the conspecific. The results of previous studies and the present study of the fish show that pre‐exposing an individual to the same type of conspecifics could elicit diverse, sometimes opposite, behavioural responses depending on how the individual is permitted to interact with the conspecific.     

Physiological Daily Inhalation Rates for Free-Living Individuals Aged 1 Month to 96 Years,Using Data from Doubly Labeled Water Measurements: A Proposal for Air Quality Criteria,Standard Calculations and Health Risk Assessment

Reported disappearance rates of oral doses of doubly labeled water (²H₂O and H₂ ¹⁸O) in urine, monitored by gas-isotope-ratio mass spectrometry for an aggregate period of over 30,000 days and completed with indirect calorimetry and nutritional balance measurements, have been used to determine physiological daily inhalation rates for 2210 individuals aged 3 weeks to 96 years. Rates in m³/kg-day for healthy normal-weight individuals (n = 1252) were higher by 6 to 21% compared to their overweight/obese counterparts (n = 679). Rates for healthy normal-weight males and females drop by about 66 to 75% within the course of a lifetime. Infants and children between the age of 3 weeks to less than 7 years inhale 1.6 to 4.3 times more air (0.395 ± 0.048 to 0.739 ± 0.071 m³/kg-day, mean ± S.D., n = 581) than adults aged 23 to 96 years (0.172 ± 0.037 to 0.247 ± 0.039 m³/kg-day, n = 388). The 99th percentile rate of 0.725 m³/kg-day based on measurements for boys aged 2.6 to less than 6 months is recommended for air quality criteria and standard calculation for non-carcinogenic compounds pertaining to individuals of any age or gender (normality confirmed using the Shapiro-Wilk test, p ≥ 0.05). This rate is 2.5-fold more protective than the daily inhalation estimate of 0.286 m³/kg-day published by the Federal Register in 1980 (i.e., 20 m³/day for a 70-kg adult). It ensures that very few newborns aged 1 month and younger, less than 1% of infants aged 2.6 to less than 6 months and of course no older individuals up to 96 years of age inhale more toxic chemicals than associated safe doses which are not anticipated to result in any adverse effects in humans, when air concentration reaches the resulting air quality criteria and standard values. This rate is also protective for underweight, overweight, and obese individuals. Finally, as far as newborns are concerned, a rate of 0.956 m³/kg-day based on the 99th percentile estimates is recommended for short-term criteria and standard calculations for toxic chemicals that yield adverse effects over instantaneous to short-term duration.     

Why are diploid genomes widespread and dominant mutations rare?

We have used the sexual Penna ageing model to show that the relation between dominance and recessiveness could be a force which optimizes the genome size. While the possibility of complementation of the damaged allele by its functional counterparts (recessiveness) leads to the redundancy of genetic information, the dominant effect of defective genes tends to diminish the number of alleles fulfilling the same function. Playing with the fraction of dominant loci in the genome it is possible to obtain the condition where the diploid state of the genome is optimal. If the status of each bit position as dominant or recessive mutations is changed for each individual randomly and rarely, then after a long time a stationary equilibrium of many recessive and few dominant loci is established in the sexual Penna model. This effect vanishes if the same changing distribution of dominant loci applies to all individuals.     

Genetic Variability of Adult Body Mass Index: A Longitudinal Assessment in Framingham Families

Objective: To explore the contribution of genetics to the mean, SD, maximum value, maximum less the mean, and change over time in body mass index (BMI) and the residual of body weight after adjustment for height. BMI is frequently used as a general indicator of obesity because of its ease and reliability in ascertainment. Cross‐sectional twin and family studies have shown a moderate‐to‐substantial genetic component for BMI. However, the contribution of genetics to the long‐term average, variability, or change over time in BMI is less clear. Research Methods and Procedures: Longitudinal data from the Framingham heart study were used to create pedigrees of age‐matched individuals. Heritability estimates were derived using variance‐decomposition methods on a total of 1051 individuals from 380 extended pedigrees followed for a period of 20 years. All subjects were followed from approximately age 35 to 55 years. Results: Moderate heritability estimates were found for the mean BMI (h² = 0.37), maximum BMI (h² = 0.40), and the mean residual of body weight (h² = 0.36). Low heritability estimates (h² ? 0.20) were found for the maximum less the mean in BMI and the SDs of BMI and residual of body weight. No additive genetic contribution was found for the average change over time in BMI or the residual of body weight. Discussion: These findings suggest that there is a significant genetic component for the magnitude of BMI throughout an individual's middle‐adult years; however, little evidence was found for a genetic contribution to the variability or rate of change in an individual's BMI.     

Evaluation of model fit of inferred admixture proportions

Model based methods for genetic clustering of individuals, such as those implemented in structure or ADMIXTURE, allow the user to infer individual ancestries and study population structure. The underlying model makes several assumptions about the demographic history that shaped the analysed genetic data. One assumption is that all individuals are a result of K homogeneous ancestral populations that are all well represented in the data, while another assumption is that no drift happened after the admixture event. The histories of many real world populations do not conform to that model, and in that case taking the inferred admixture proportions at face value might be misleading. We propose a method to evaluate the fit of admixture models based on estimating the correlation of the residual difference between the true genotypes and the genotypes predicted by the model. When the model assumptions are not violated, the residuals from a pair of individuals are not correlated. In the case of a bad fitting admixture model, individuals with similar demographic histories have a positive correlation of their residuals. Using simulated and real data, we show how the method is able to detect a bad fit of inferred admixture proportions due to using an insufficient number of clusters K or to demographic histories that deviate significantly from the admixture model assumptions, such as admixture from ghost populations, drift after admixture events and nondiscrete ancestral populations. We have implemented the method as an open source software that can be applied to both unphased genotypes and low depth sequencing data.     

Cellular senescence and DNA synthesis : Thymidine incorporation as a measure of population age in human diploid cells

For the human diploid cell lines WI-38 and WI-26, the percentage of cells able to incorporate ³H-TdR into their nuclei under standard conditions declines as a function of either elapsed calendar time or the number of population doublings. The rate of decline varies for each population depending on its overall lifespan. If, however, the percent of labelled nuclei is considered as a function of the percent of lifespan completed (i.e., the number of population doublings at time t/total number of population doublings attained during lifespan of the culture), a highly reproducible relationship is found. Using 10% class intervals for the incidence of labelled nuclei, it is possible to distinguish the ‘age’ of populations which differ by about 5 passages or less. With this simple technique, one can evaluate simultaneously and in a reproducible way the current age of the culture, as well as the remaining proliferative capacity of the population.     

Contributions of high- and low-quality patches to a metapopulation with stochastic disturbance

Studies of time-invariant matrix metapopulation models indicate that metapopulation growth rate is usually more sensitive to the vital rates of individuals in high-quality (i.e., good) patches than in low-quality (i.e., bad) patches. This suggests that, given a choice, management efforts should focus on good rather than bad patches. Here, we examine the sensitivity of metapopulation growth rate for a two-patch matrix metapopulation model with and without stochastic disturbance and found cases where managers can more efficiently increase metapopulation growth rate by focusing efforts on the bad patch. In our model, net reproductive rate differs between the two patches so that in the absence of dispersal, one patch is high quality and the other low quality. Disturbance, when present, reduces net reproductive rate with equal frequency and intensity in both patches. The stochastic disturbance model gives qualitatively similar results to the deterministic model. In most cases, metapopulation growth rate was elastic to changes in net reproductive rate of individuals in the good patch than the bad patch. However, when the majority of individuals are located in the bad patch, metapopulation growth rate can be most elastic to net reproductive rate in the bad patch. We expand the model to include two stages and parameterize the patches using data for the softshell clam, Mya arenaria. With a two-stage demographic model, the elasticities of metapopulation growth rate to parameters in the bad patch increase, while elasticities to the same parameters in the good patch decrease. Metapopulation growth rate is most elastic to adult survival in the population of the good patch for all scenarios we examine. If the majority of the metapopulation is located in the bad patch, the elasticity to parameters of that population increase but do not surpass elasticity to parameters in the good patch. This model can be expanded to include additional patches, multiple stages, stochastic dispersal, and complex demography.     

Evolution of the rate of biological aging using a phenotype based computational model

In this work I introduce a simple model to study how natural selection acts upon aging, which focuses on the viability of each individual. It is able to reproduce the Gompertz law of mortality and can make predictions about the relation between the level of mutation rates (beneficial/deleterious/neutral), age at reproductive maturity and the degree of biological aging. With no mutations, a population with low age at reproductive maturity R stabilizes at higher density values, while with mutations it reaches its maximum density, because even for large pre-reproductive periods each individual evolves to survive to maturity. Species with very short pre-reproductive periods can only tolerate a small number of detrimental mutations. The probabilities of detrimental (P_d) or beneficial (P_b) mutations are demonstrated to greatly affect the process. High absolute values produce peaks in the viability of the population over time. Mutations combined with low selection pressure move the system towards weaker phenotypes. For low values in the ratio P_d/P_b, the speed at which aging occurs is almost independent of R, while higher values favor significantly species with high R. The value of R is critical to whether the population survives or dies out. The aging rate is controlled by P_d and P_b and the amount of the viability of each individual is modified, with neutral mutations allowing the system more “room” to evolve. The process of aging in this simple model is revealed to be fairly complex, yielding a rich variety of results.     

Age-biased parasitism and density-dependent distribution of fleas (Siphonaptera) on a desert rodent

Parasites often confront conflicting demands when evaluating and distributing themselves among host individuals, in order to attain maximum reproductive success. We tested two alternative hypotheses about host preference by fleas in relation to the age of their rodent host. The first hypothesis suggests that fleas select adult over juvenile rodents because the latter represent a better nutritional resource (the “well-fed host” hypothesis), whereas the second hypothesis suggests that fleas prefer the weaker and less resistant juveniles because they are easier to colonise and exploit (“poorly fed host” hypothesis). We sampled fleas (Synosternus cleopatrae) on the gerbil (Gerbillus andersoni) in 23 different plots in the Negev desert and found an unequal distribution of fleas between adult and juvenile hosts. Furthermore, flea distribution changed as a function of flea density—from juvenile-biased flea parasitism (the “poorly fed host” hypothesis) at low densities to adult-biased flea parasitism (the “well-fed host” hypothesis) at high densities. Other factors that influenced flea preference were soil temperature and the presence of ticks. These results suggest that host selection is not an explicit alternative choice between adults and juveniles (“well-fed host” versus “poorly fed host” hypotheses), but rather a continuum where the distribution between adults and juveniles depends on host, parasite, and environmentally related factors.     

A computer simulation evaluation of the role of mutations in finite populations on the response to directional selection: The generations required to attain maximum genetic variance

Summary The role of mutations in finite populations on response to artificial selection was investigated by a computer simulation model designed to mimic the biological model of pupal weight of Tribolium. Given the model, the results showed that with selection about 25–55 generations were needed for genetic variances to reach a maximum value depending on population size, selection intensity, and gene number. When effective population size was larger than 40 or the intensity of selection was high (less than 50% selected), selection had a dramatic effect in reducing the time to approach the maximum point of genetic variance. Furthermore, the genetic variance after that point often declined as a function of selection instead of remaining at a steady state in the subsequent generations.     

Survival Expectations of the Obese: Is Excess Mortality Reflected in Perceptions?

Objective: This study compared self‐reported subjective life expectancy (i.e., probability of living to age 75) for normal‐weight, overweight, and obese weight groups to examine whether individuals are internalizing information about the health risks due to excessive weight. Research Methods and Procedures: Using data from the Health and Retirement Study, a total of 9035 individuals 51 to 61 years old were analyzed by BMI category. The primary outcome measure was individuals’ reports about their own expectations of survival to age 75. Absolute and relative risks of survival were compared with published estimates of survival to age 75. Results: Consistently, higher levels of BMI were associated with lower self‐estimated survival probabilities. Differences relative to normal weight ranged from 4.9% (p < 0.01) for male nonsmokers to 8.8% (p < 0.001) for female nonsmokers. However, these differences were substantially less than those obtained from published survival curve estimates, suggesting that obese individuals tended to underestimate mortality risks. Discussion: Individuals appeared to underestimate the mortality risks of excessive weight; thus, knowledge campaigns about the risks of obesity should remain a top priority.     

Waist circumference correlates with metabolic syndrome indicators better than percentage fat

Objective : Percent fat is often considered the reference for establishing the magnitude of adipose tissue accumulation and the risk of excess adiposity. However, the increasing recognition of a strong link between central adiposity and metabolic disturbances led us to test whether waist circumference (WC) is more highly correlated with metabolic syndrome components than percent fat and other related anthropometric measures such as BMI. Research Methods and Procedures : BMI, WC, and percent fat, measured by DXA, were evaluated in 1010 healthy white and African‐American men and women [age, 48.3 ± 17.2 (standard deviation) years; BMI, 27.0 ± 5.3 kg/m²]. The associations of BMI, WC, and percent fat with age and laboratory‐adjusted health risk indicators (i.e., serum glucose, insulin, triglycerides, high‐density lipoprotein cholesterol, blood pressure) in each sex and ethnicity group were examined. Results : For 18 of 24 comparisons, the age‐ and laboratory‐adjusted correlations were lowest for percent fat and in 16 of 24 comparisons were highest for WC. Fifteen of the between‐method differences reached statistical significance. With health risk indicator as the dependent variable and anthropometric measures as the independent variable, the contribution of percent fat to the WC regression model was not statistically significant; in contrast, adding WC to the percent fat regression model did make a significant independent contribution for most health risk indicators. Discussion : WC had the strongest associations with health risk indicators, followed by BMI. Although percent fat is a useful measure of overall adiposity, health risks are best represented by the simply measured WC.     

SURVIVORSHIP AND FECUNDITY OF THE POLYCARPIC PERENNIAL MENTZELIA NUDA (LOASACEAE) IN NEBRASKA SANDHILLS PRAIRIE

Survivorship and fecundity of the polycarpic perennial Mentzelia nuda were investigated to help understand its population dynamics. Between 1978 and 1984, all 685 individuals found in a Nebraska sandhills prairie plot were marked and their fate followed. Three plants lived seven years, but the average lifespan was less than two years. Most plants spent their first year as nonflowering rosettes: only 9% flowered the first summer after germination. Overall, first-year survivorship ranged from 0.20 to 0.50 between 1978 and 1984. Fifty-two percent of rosettes survived to flower. Survivorship of flowering individuals was about the same as the survivorship of rosettes, although actual survivorships varied significantly between years. Both rainfall and age affected survivorship and fecundity.     

Age- and density-dependent population dynamics in static and variable environments

We consider a general model of a single-species population with age- and density-dependent per capita birth and death rates. In a static environment we show that if the per capita death rate is independent of age, then the local stability of any stationary state is guaranteed by the requirement that, in the region of the steady state, the density dependence of the birth rate should be negative and that of the death rate positive. In a variable environment we show that, provided the system is locally stable, small environmental fluctuations will give rise to small age structure and population fluctuations which are related to the driving environmental fluctuations by a simple “transfer function.” We illustrate our general theory by examining a model with a per capita death rate which is age and density independent and a per capita birth rate which is zero up to some threshold age a₀, adopts a finite density-dependent value up to a maximum age a_o + α, and is zero thereafter. We conclude from this model that resonance due specifically to single-species age-structure effects will only be of practical importance in populations whose members have a life cycle consisting of a long immature phase followed by a short burst of intense reproductive effort (α a_o).     

Sexual selection,redundancy and survival of the most beautiful

A model is described of a highly redundant complex organism that has overlapping banks of genes such that each vital function is specified by several different genetic systems. This generates a synergistic profile linking probability of survival to the number of deleterious mutations in the genome. Computer models show that there is a dynamic interaction between the mean number of new deleterious mutations per generation (X), the mean number of deleterious mutations in the genome of the population (Y) and percentage zygote survival (Zs). IncreasedX leads to increasedY and a fall in Zs but it takes several generations before a new equilibrium is reached. If sexual attraction is influenced by the number of deleterious mutations in the genome of individuals thenY is reduced and Zs increased for any given value ofX. This fall inY and rise in Zs is more marked in polygamous than monogamous mating systems. The model is specified such that deleterious mutations can occur without any observable or measurable effect on function. Thus sexual selection, in this organism, for low levels of deleterious mutations cannot be based on assessment of performance. Instead it is based on a simple symmetrical surface pattern that is flawlessly reproduced by organisms with no deleterious mutations, but is less than perfect, and therefore less attractive, if genetic systems have been deleted. A complex vital task requires a system with a high level of redundancy that acts so that the loss of one component has no observable effect and therefore cannot be used for sexual selection. The reproduction of a beautiful surface pattern also requires a low error, high redundancy genetic system; however, in this case there is advantage if a single deleterious mutation produces a recognisable change. This leads to the conclusion that sexual selection and sexual attraction should be based on beauty rather than utility, and explains the common observation in nature that it is the most beautiful that survive.