Genetic sex determination, sex chromosome size and sex-specific lifespans across tetrapods.

Sex differences in lifespan are ubiquitous across the tree of life and exhibit broad taxonomic patterns that remain a puzzle, such as males living longer than females in birds and vice versa in mammals. The prevailing unguarded X hypothesis explains sex differences in lifespan by differential expression of recessive mutations on the X or Z chromosome of the heterogametic sex, but has only received indirect support to date. An alternative hypothesis is that the accumulation of deleterious mutations and repetitive elements on the Y or W chromosome might lower the survival of the heterogametic sex ('toxic Y' hypothesis). Here, we use a new database to report lower survival of the heterogametic relative to the homogametic sex across 136 species of birds, mammals, reptiles and amphibians, as expected if sex chromosomes shape sex-specific lifespans, and consistent with previous findings. We also found that the relative sizes of both the X and the Y chromosomes in mammals (but not the Z or the W chromosomes in birds) are associated with sex differences in lifespan, as predicted by the unguarded X and the 'toxic Y'. Furthermore, we report that the relative size of the Y is negatively associated with male lifespan in mammals, so that small Y size correlates with increased male lifespan. In theory, toxic Y effects are expected to be particularly strong in mammals, and we did not find similar effects in birds. Our results confirm the role of sex chromosomes in explaining sex differences in lifespan across tetrapods and further suggest that, at least in mammals, 'toxic Y' effects may play an important part in this role.

Sex-specific paternal age effects on offspring quality in Drosophila melanogaster.

Advanced paternal age has been repeatedly shown to modulate offspring quality via male- and/or female-driven processes, and there are theoretical reasons to expect that some of these effects can be sex-specific. For example, sex allocation theory predicts that, when mated with low-condition males, mothers should invest more in their daughters compared to their sons. This is because male fitness is generally more condition-dependent and more variable than female fitness, which makes it less risky to invest in female offspring. Here, we explore whether paternal age can affect the quality and quantity of offspring in a sex-specific way using Drosophila melanogaster as a model organism. In order to understand the contribution of male-driven processes on paternal age effects, we also measured the seminal vesicle size of young and older males and explored its relationship with reproductive success and offspring quality. Older males had lower competitive reproductive success, as expected, but there was no difference between the offspring sex ratio of young and older males. However, we found that paternal age caused an increase in offspring quality (i.e., offspring weight), and that this increase was more marked in daughters than sons. We discuss different male- and female-driven processes that may explain such sex-specific paternal age effects.

Fitness benefits of dietary restriction.

Dietary restriction (DR) improves survival across a wide range of taxa yet remains poorly understood. The key unresolved question is whether this evolutionarily conserved response to temporary lack of food is adaptive. Recent work suggests that early-life DR reduces survival and reproduction when nutrients subsequently become plentiful, thereby challenging adaptive explanations. A new hypothesis maintains that increased survival under DR results from reduced costs of overfeeding. We tested the adaptive value of DR response in an outbred population of Drosophila melanogaster fruit flies. We found that DR females did not suffer from reduced survival upon subsequent re-feeding and had increased reproduction and mating success compared to their continuously fully fed (FF) counterparts. The increase in post-DR reproductive performance was of sufficient magnitude that females experiencing early-life DR had the same total fecundity as continuously FF individuals. Our results suggest that the DR response is adaptive and increases fitness when temporary food shortages cease.

Condition-dependent mortality exacerbates male (but not female) reproductive senescence and the potential for sexual conflict.

Disentangling the relationship between age and reproduction is central to understand life-history evolution, and recent evidence shows that considering condition-dependent mortality is a crucial piece of this puzzle. For example, nonrandom mortality of 'low-condition' individuals can lead to an increase in average lifespan. However, selective disappearance of such low-condition individuals may also affect reproductive senescence at the population level due to trade-offs between physiological functions related to survival/lifespan and the maintenance of reproductive functions. Here, we address the idea that condition-dependent extrinsic mortality (i.e. simulated predation) may increase the age-related decline in male reproductive success and with it the potential for sexual conflict, by comparing reproductive ageing in Drosophila melanogaster male/female cohorts exposed (or not) to condition-dependent simulated predation across time. Although female reproductive senescence was not affected by predation, male reproductive senescence was considerably higher under predation, due mainly to an accelerated decline in offspring viability of 'surviving' males with age. This sex-specific effect suggests that condition-dependent extrinsic mortality can exacerbate survival-reproduction trade-offs in males, which are typically under stronger condition-dependent selection than females. Interestingly, condition-dependent extrinsic mortality did not affect mating success, hinting that accelerated reproductive senescence is due to a decrease in male post-copulatory fitness components. Our results support the recent proposal that male ageing can be an important source of sexual conflict, further suggesting this effect could be exacerbated under more natural conditions.

Multigenerational downregulation of insulin/IGF-1 signaling in adulthood improves lineage survival, reproduction, and fitness in Caenorhabditis elegans supporting the developmental theory of ageing.

Adulthood-only downregulation of insulin/IGF-1 signaling (IIS), an evolutionarily conserved pathway regulating resource allocation between somatic maintenance and reproduction, increases life span without fecundity cost in the nematode, Caenorhabditis elegans. However, long-term multigenerational effects of reduced IIS remain unexplored and are proposed to carry costs for offspring quality. To test this hypothesis, we ran a mutation accumulation (MA) experiment and downregulated IIS in half of the 400 MA lines by silencing daf-2 gene expression using RNA interference (RNAi) across 40 generations. Contrary to the prediction, adulthood-only daf-2 RNAi reduced extinction of MA lines both under UV-induced and spontaneous MA. Fitness of the surviving UV-induced MA lines was higher under daf-2 RNAi. Reduced IIS increased intergenerational F1 offspring fitness under UV stress but had no quantifiable transgenerational effects. Functional hrde-1 was required for the benefits of multigenerational daf-2 RNAi. Overall, we found net benefit to fitness from multigenerational reduction of IIS and the benefits became more apparent under stress. Because reduced daf-2 expression during development carries fitness costs, we suggest that our findings are best explained by the developmental theory of ageing, which maintains that the decline in the force of selection with age results in poorly regulated gene expression in adulthood.

Sex ratio at mating does not modulate age fitness effects in Drosophila melanogaster.

Understanding the effects of male and female age on reproductive success is vital to explain the evolution of life history traits and sex-specific aging. A general prediction is that pre-/postmeiotic aging processes will lead to a decline in the pre- and postcopulatory abilities of both males and females. However, in as much the sexes have different strategies to optimize their fitness, the decline of reproductive success late in life can be modulated by social context, such as sex ratio, in a sex-specific manner. In this study, we used Drosophila melanogaster to investigate whether sex ratio at mating modulates age effects on male and female reproductive success. As expected, male and female age caused a decrease in reproductive success across male-biased and female-biased social contexts but, contrary to previous findings, social context did not modulate age-related fitness decline in either of the two sexes. We discuss these results in the light of how sex ratio might modulate pre-/postcopulatory abilities and the opportunity for inter- and intrasexual competition in D. melanogaster, and generally suggest that social context effects on these processes are likely to be species specific.

The "unguarded-X" and the genetic architecture of lifespan: Inbreeding results in a potentially maladaptive sex-specific reduction of female lifespan in Drosophila melanogaster.

Sex differences in ageing and lifespan are ubiquitous in nature. The "unguarded-X" hypothesis (UXh) suggests they may be partly due to the expression of recessive mutations in the hemizygous sex chromosomes of the heterogametic sex, which could help explain sex-specific ageing in a broad array of taxa. A prediction central to the UX hypothesis is that inbreeding will decrease the lifespan of the homogametic sex more than the heterogametic sex, because only in the former does inbreeding increase the expression of recessive deleterious mutations. In this study, we test this prediction by examining the effects of inbreeding on the lifespan and fitness of male and female Drosophila melanogaster across different social environments. We found that, across social environments, inbreeding resulted in a greater reduction of female than male lifespan, and that inbreeding effects on fitness did not seem to counterbalance sex-specific effects on lifespan, suggesting the former are maladaptative. Inter- and intra-sexual correlation analyses also allowed us to identify evidence of an underlying joint genetic architecture for inbreeding effects on lifespan. We discuss these results in light of the UXh and other alternative explanations, and suggest that more attention should be paid to the possibility that the "unguarded-X" may play an important role in the evolution of sex-specific lifespan.

Controlled release of a hydrophilic drug from coaxially electrospun polycaprolactone nanofibers.

A recent approach for controlled release of drugs is the production of core-shell fibers via modified coaxial electrospinning where a shell solution which is not fully electrospinnable can be used. In this study, this technique was used for achieving the controlled release of a model hydrophilic drug (ampicillin) which is known to have a low compatibility with the polymer (polycaprolactone). A partially electrospinnable shell fluid (4% (w/v) polycaprolactone (PCL) solution) and a fully electrospinnable core fluid (10% (w/v) PCL, 2% (w/v) ampicillin solution) were used in order to create ampicillin-loaded PCL nanofibers covered by a PCL shield. Scanning electron microscopy and optical microscopy images proved that the membranes have core-shell structured nanofibers. Fourier transform infrared spectroscopy demonstrated that some compatibility might be present between ampicillin and PCL. Finally, drug release studies showed that the drug release kinetics of core-shell products is closer to zero-order kinetics while the drug release kinetics of single electrospinning of the core resulted with serious burst release. Together, these imply that the application area of modified coaxial electrospinning in controlled release could be expanded to polymers and drugs with low compatibility.