Prediction of the human life expectancy

We have simulated demographic changes in the human population using the Penna microscopic model, based on the simple Monte Carlo method. The results of simulations have shown that during a few generations changes in the genetic pool of a population are negligible, while improving the methods of compensation of genetic defects or genetically determined proneness to many disorders drastically affects the average life span of organisms. Age distribution and mortality of the simulated populations correspond very well to real demographic data available from different countries. Basing on the comparison of structures of real human populations and the results of simulations it is possible to predict changes in the age structure of populations in the future.     

Patentability of life and ethics

Patent law has relied in part on ethical considerations since its inception in Europe. Such considerations have been introduced more recently in the United States. Whereas the EU Directive on the protection on the occasion of the Human Genome Project of biotechnological inventions was intended to foster economic development in Europe, its implementation is outweighted by controversy about patenting life and commercialization of science. The confusion created must be cleared at the international level through harmonization of patent office policies preventing abusive commercial practices in the absence of inventiveness.     

A predictive model for life expectancy curves

Life expectancy curves have a characteristic ominous shape that has fascinated scientists for centuries. Medawar was the first to explain this shape, specifically the steeply rising proneness of an average individual to die as a function of age, in evolutionary terms. The idea was that the "selective value" of the individual decreases as it has triggered other individuals taking its place (and carrying its genes) into existence. We demonstrate that this idea can be turned into a quantitative model. The resulting 4-parameter function reproduces well two well-known life expectancy curves from the first half of this century. Moreover, the easily interpretable parameters (3 of the 4) seem intuitively reasonable.     

The Jewish–Arab divide in life expectancy in Israel

Life expectancy at birth in Israel in 2001 was 77.7 years for males and 81.6 years for females among Jews, and 74.5 and 77.8 years for males and females, respectively, among Israeli Arabs. In spite of vast improvements in health conditions of the two populations since Israel's statehood in 1948, persistent disparities in life expectancy between the two groups have challenged the Israeli socialized health care system. These disparities are influenced primarily by differences between the two population groups in infant and child mortality rates. This early study suggests that the distribution of life expectancy across localities in Israel reflects the distribution of those localities' socio-economic condition index (not including health and medical care), and the distribution of medical services. The positive association between life expectancy and the index is pronounced, however, only within the Jewish population but not among Arabs. While there may be no significant difference in life expectancy among Jews and Arabs living in poorer communities, there are fewer Arabs living in relatively affluent communities. Thus, persistent higher concentration of poverty among Arabs than among Jews has sufficed to maintain the gap in life expectancy between them. In addition, however, there are population-specific effects: wealth and education are more protective among Jews than among Arabs, while medical services are more protective among Arabs.     

Delayed motherhood decreases life expectancy of mouse offspring

This study analyzes the long-term effects of delayed motherhood on reproductive fitness and life expectancy of offspring in the mouse. Hybrid (C57BL/6JIco x CBA/JIco) first-generation (F1) females, either at the age of 10 or 51 wk, were individually housed with a randomly selected 12- to 14-wk-old hybrid male following a breeding pen system until females reached the end of their reproductive life. Reproductive fitness of second-generation (F2) females was tested from the age of 25 wk until the end of their reproductive life. In F2 males, the testing period ranged from the age of 52 wk until their natural death. Delayed motherhood of hybrid F1 female mice was associated with a decreased percentage of male F3 offspring at birth and lower life expectancy and body weight during adulthood of F2 offspring. There was, however, no evident negative effect of delayed motherhood on several reproductive fitness variables in either male or female F2 offspring. This included between-parturition interval, litter size at birth and at weaning, body weight at weaning and preweaning mortality of F3 pups, percentage of F3 litters with at least one pup cannibalized, and time at which female and male F2 offspring ceased their reproductive life. These data clearly show that delayed motherhood in the mouse is associated with negative long-term effects on offspring survival.     

Leaf palatability,life expectancy and herbivore damage

Summary Observations on leaves from plants with a wide range of life-forms, ruderals to trees, indicate that palatability to insect herbivores is strongly correlated with the life-expectancy of the leaves. The amount of damage suffered in the field is however inversely correlated with palatability; although the rate of damage is less on unpalatable leaves, their longer life means that they accumulate damage over a longer period. It is only with extremely well-defended evergreen leaves, that the total damage is less than that experienced by less palatable (but short-lived) leaves. These observations are related to the current theories on relative palatability (the apparency theory and the resource availability theory), within the framework of the habitat templet.     

Graduated change of life expectancy in mice in ontogenesis

Life expectancy of descendants of a normal female mouse and a male with an inherited growth inhibition mutation discovered in a laboratory population was investigated. The hereditability of the characteristic allows us to consider it a result of mutation. It was shown that, in mice, the curve of dependence of life expectancy on their serial number in a row of increase in life expectancy (curve of rank distribution) has step-like shape for mutant males and females, as well as for males with normal development. The first grade of mice death on the curve of rank distribution was observed at one month after their birth and was characteristic only of males and females with a mutation during the period of maximum lag in weight as compared with their normal relatives. The surviving mutants catch up to the normally developing individuals within two months and externally become indistinguishable from them. The subsequent grades of death in mutants and normal males coincide on the time axis. The steps are absent on the rank curves of life expectancy of normally developing females. The time intervals between the steps are reproduced in parallel groups of mice and, hence, are not casual deviations from theoretical curves and are of a regular nature. The discovered phenomenon is interpreted within the scope of a hypothesis about the realization of the genetic program of ontogenesis, which provides periodic change of vitality stages with stages of sensitivity to external risk factors, which increase the probability of death, by mice. Absence of such stages in the group of normally developing females can be explained by shifts in development, which are produced by the irregular performance of reproductive functions.     

The cost of living longer. Fertility trades with immunity and life expectancy

There is an ancient balance struck between immunity and fertility. The ongoing trend in developed societies to have fewer children and later in life, might influence human life expectancy and disease susceptibility.Sexual reproduction and the mixing of alleles that it entails boosts diversity, but also poses a dilemma for individual organisms. Given that each organism has ultimately limited resources for reproduction, maintenance and immunity, the choice between fertility and long-term survival is one between two opposite poles of selection that operate across many animal and plant species. The balance between fertility and immunity has direct implications for human health; indeed a growing body of work is investigating the links between disease and reproductive biology. Moreover, epidemiological data shows that humans, especially in developed countries and particularly women, are becoming less fertile, but more immune to infectious and other diseases. This, in addition to factors such as improved healthcare, is further increasing human lifespan in wealthy societies.The hypothesis that investing more energy and resources into maintenance and immunity comes at the expense of fertility was first proposed by Thomas Kirkwood (1977), now Director of the Institute for Ageing and Health at Newcastle University in the UK. His theory was supported by epidemiological and historical data (Westendorp & Kirkwood, 1998), as well as animal experiments and molecular evidence. Yet, the exact nature of the link between reproduction and immunity has remained elusive.One problem, at least for plant and animal species that have internal fertilization, is the cost of this reproductive strategy whereby gametes from one partner, usually the male, enter the other. This is the heart of the sexual immunity problem, according to Michael Siva-Jothy, an entomologist at Sheffield University in the UK, whose interest in this relationship between reproduction and immunity has led him to study the phenomenon in vertebrates. “I would say, when you go from external to internal fertilisation, you create a huge problem,” he said. “It''s the same problem probably across all taxa, in that recipients of gametes are faced with how to defend their internal environment from non self, while allowing sperm to get through. Sperm are non self even to males, so must be in females.”The balance between fertility and immunity has direct implications for human health…Moreover, the link between reproduction and immunity extends beyond the female genital tract to include pregnancy in mammals and male fertility. A joint study between Princeton University in the USA and Edinburgh University in the UK found that among a population of isolated sheep in the Outer Hebrides—islands off the coast of Scotland—both males and females with high levels of antibodies were able to survive the occasional harsh winters that occur there, but reproduced less than did sheep with lower levels of antibodies during less harsh winters (Graham et al, 2010). During intervening periods, often lasting several years, the number of individuals with lower levels of antibodies within the population would increase, before being reduced again when the next harsh winter arrived.The fact that both male and female sheep were affected rules out anything to do with the female genital tract. “We do not know why the autoantibody responses were associated with reduced annual breeding success,” commented Andrea Graham, lead author of the study from Princeton University. “The same pattern occurred in both males and females, which suggests a resource allocation ‘trade-off''.”“I would say, when you go from external to internal fertilisation, you create a huge problem.”According to David Schneider, whose laboratory at Stanford University in the USA specializes in innate immunity and host–parasite interactions in Drosophila, the resource theory—that a living organism has limited resources available for growth, maintenance and reproduction—plays a major role in the relationship between fertility and immunity. “There seems to be some sort of limit on how much a body can do,” he said. “We can''t just keep doing more and there is a reason that we don''t have our immune response on all of the time.”By its nature, the resource theory is hard to establish beyond all doubt, but there is growing evidence that resource allocation plays an important role in a third instance in humans and probably all mammals: an internal conflict between mother and fetus. This too involves a trade-off, but for a different reason, because the interests of the fetus and the mother do not exactly coincide. The fetus, half of whose genes are paternal, wants to obtain as much of the mother''s resources as possible to optimize its growth during pregnancy. The mother''s best interest, however, lies in distributing her available resources equally among all the fetuses she will conceive during her lifetime. This conflict is played out through the immune systems of father, fetus and mother, and in particular through the major histocompatibility class (MHC) molecules. During pregnancy, the mother exhibits an inflammatory response to the paternal MHC proteins expressed by the fetus, which is often cited as evidence for the maternal–fetal conflict theory.A successful pregnancy therefore requires that the mother''s body tolerates the presence of MHCs and other antigens of paternal origin that are expressed by the fetus. There is some evidence that the father can manipulate this response: if the paternal MHC proteins are very different to the maternal ones, this tends to stimulate growth of the placenta, thereby increasing the resources available to the fetus (Madeja et al, 2011).A successful pregnancy therefore requires that the mother''s body tolerates the presence of MHCs and other antigens of paternal origin that are expressed by the fetus''The conflict theory has implications for the health of both fetus and mother, since the inflammatory response can cause significant harm or even death to both. It can, for example, cause an excessive immunological response to low virulence bacteria such as Fusobacteria that are commonly present in the upper genital tract and normally cause few problems. This excessive immune response is associated with premature delivery (Gomez et al, 1997). There is also evidence that pre-eclampsia—a systemic maternal disease that is characterized by hypertension and proteinuria, and which is potentially fatal to both mother and fetus—is caused in some cases by maternal–fetal conflict (Ness, 2004).According to David van Bodegom from the Department of Gerontology and Geriatrics at Leiden University in the Netherlands, the strength of the mother''s immunity can determine whether conception will occur in the first place. He referred to a study finding that women attending IVF clinics because of problems conceiving children were much more likely to suffer spontaneous abortions and at the same time had elevated immune function.Van Bodegom suggested that such findings have significant societal implications, given the negative selection pressure against fertility in women caused by the trend to have smaller families. “In the past, the next generation would be produced by a limited number of very fertile women who had large families, while now all women have 1.8 to 2.4 children depending on the country,” he said. Less fertile mothers receive assistance through IVF and other measures to conceive, while more fertile ones use contraceptive drugs and other methods to limit their reproduction. “So now only a few children are descendants of very fertile women,” said van Bodegom.There is a parallel trend in wealthier nations towards having children later in life. “The Netherlands has the European record for the highest average age of [mothers giving birth to their] first child, I think now 30 years,” said van Bodegom. The first trend suggests that fertility problems among women will increase, as will the need for assistance. The second trend towards having children later would select for women who retain their fertility for longer.… women with late menopauses tend to live longer, which may suggest they have stronger immune systems and in turn perhaps lower overall fertilityThe two trends—lower fertility overall but retaining it for longer—seem to pull in opposite directions but might actually favour the same women. According to van Bodegom, women with late menopauses tend to live longer, which might suggest they have stronger immune systems and in turn perhaps lower overall fertility. This is still speculation at present, but there is a clear correlation between the late onset of menopause and longevity (Ossewaarde et al, 2005). Selection pressure for delayed menopause onset should therefore lead to increased life expectancy among women, van Bodegom suggested.But there is a downside to late motherhood: the high physiological demands of pregnancy itself. A recent study in the UK found that although overall levels of death during pregnancy or childbirth had decreased dramatically since surveys began in 1952, the maternal death rate from indirect causes had actually increased over the last 20 years (Cantwell et al, 2011). These indirect causes include cardiac disease, hypertension, diabetes and neurological disorders brought on or accentuated by pregnancy.… exposure to heavy metals can also trigger the production of antibodies acting against sperm and cause male infertility…The report prompted David Williams, a Consultant Obstetric Physician at University College Hospital in London, and others to argue in the British Medical Journal that this rise in death rate was the result of an increase in average age of pregnant mothers (Nelson-Piercy et al, 2011). Older women tend to weigh more, which increases the risk of diabetes and hypertension in particular during pregnancy, Williams argued. Older women were are also less well equipped to deal with the physical and physiological rigours of pregnancy, and this in turn translated into increased risk of disease and complications. Given that this trend towards later pregnancies is unlikely to be reversed, Williams and his colleagues have called for more specialist physicians and greater awareness among all doctors.Although the greatest focus on the links between fertility, immunity and longevity has been on women, there is mounting evidence that the story includes men. Some studies demonstrate a link between immunity and spermatogenesis in humans, mostly showing that sperm itself is recognized as non-self in men and can trigger the production of anti-sperm antibodies (ASAs). This would explain why there is a barrier between the testes, where sperm are produced and stored, and the blood: to prevent sperm antigens from leaking out and triggering ASA production.Yet, the barrier is not impenetrable: chronic infection of the genitals can cause the production of ASAs, perhaps by maintaining a high level of immunity. Moreover, exposure to heavy metals can also trigger the production of antibodies acting against sperm and cause male infertility, which would partly explain an overall decline in male fertility observed during the past half century or more in some countries, possibly triggered by exposure to mercury in dental tooth fillings (Podzimek et al, 2005).However, despite the presence of ASAs from the man, sperm are still able to reach the oocyte. Even so, some researchers have suggested that by binding to the sperm, ASAs make it unable to complete the so-called acrosome reaction needed to penetrate the oocyte (Bohring et al, 2004). This reaction occurs in some form in almost all sexually reproducing species after the fusion between sperm and oocyte, and enables the acrosome—a cap-like structure on the head of the sperm—to release its contents. These contents include surface antigens and enzymes that break down the coat of the oocyte and allow fertilization to occur. Antibodies attached to the sperm head can prevent the all-important acrosome reaction from taking place.… humans in developed societies have been subject to an extraordinary selective shift during the past half century, which increased life expectancy and immunity at the cost of fertilityImmunity therefore seems linked to fertility in both men and women, although it remains to be seen whether the inverse relationship applies in men: that is, individuals who are more fertile also have lower levels of immunity. However, the fate of sheep in the Outer Hebrides suggests this might well be the case. In fact, another epidemiological study of human longevity and reproductive success indicates that there is such a trade-off in both men and women (Thomas et al, 2000).These diverse data from various fields show that humans in developed societies have been subject to an extraordinary selective shift during the past half century, which increased life expectancy and immunity at the cost of fertility. It is also clear that this development is not over yet and that it will have profound health and social implications for both sexes in future generations.     

The life expectancy of phlebotomine sandflies: first field estimates from southern France

Abstract. 1. A field study of Phlebotomus ariasi Tonnoir, the vector of Leishmania infantum Nicolle in southern France, addressed the following questions: Is it possible to estimate reliably the life expectancy of this sandfly; can spatial or temporal variation in the life expectancy be detected, and is such variation significant for disease transmission? 2. Life expectancy was estimated by examining follicular relics in the ovaries of more than ten thousand females caught in light traps at seven sites in the Cévennes and the Garrigues, throughout their active period in 1985 and 1986. Whilst the distinction between nulliparous and parous flies was easily made, assessments of the number of times a parous fly had laid eggs were unreliable. Best estimates of life expectancy were therefore calculated from the parous rate. 3. Large samples collected from one site in the Cevennes in both years gave very similar estimates of life expectancy. 4. There was also no significant difference between estimates obtained from the Cévennes and the Garrigues, despite their distinct vegetation and climates. Therefore, large regional differences in sandfly population size and the prevalence of canine leishmaniasis cannot be explained by a difference in adult survival rate. 5. With no systematic annual or regional variation, a useful mean life expectancy can be calculated from the data collected at all sites in both years. It is 1.54 (SE 0.04) ovarian cycles. However, this estimate is sensitive to the assumption that survival rate is a discrete rather than a continuous variable. 6. Local variation in the parous rate may be associated with the proximity of traps to P.ariasi emergence sites.