Sexual Dimorphism In Age Research Articles

SA70 - SEX-STRATIFIED ANALYSIS OF OBSESSIVE-COMPULSIVE DISORDER REVEALS MINOR DIFFERENCES IN GENETIC ARCHITECTURE

Background Obsessive-Compulsive Disorder (OCD), a heritable neurobehavioral disorder, demonstrates sexual dimorphism in age of onset and clinical presentation, suggesting a possible sex difference in genetic architecture. Here, we present the first genome-wide assessment of sex-specific genetic architecture of OCD on currently the largest OCD cohort available from the Psychiatric Genomics Consortium (total cases and controls N=9,870 after quality control, 1:1.4 male/female ratio). Methods First, we performed a sex-stratified meta-GWAS to identify specific autosomal and sex chromosome genetic variants differentially associated to OCD risk in each of the sexes. Second, we assessed whether the most heterogeneous OCD risk alleles and top (p Results There were no genome-wide significant associations in either sex. Sex heterogenous SNPs (including and excluding SNPs in the HLA region) were strongly enriched for immune expression quantitative trait loci (p Discussion We present the first genome-wide assessment of sex-specific genetic architecture of OCD. We identified minor sex differences in genetic architecture of OCD, and although the sex-stratified sample size is likely too small to identify variants with small effect, we have developed a robust analytic pipeline for sex-stratified genetic analysis which will be applied in the near future to OCD as larger cohorts become available. The pipeline will also be applied to additional phenotypes where a sex bias in genetic effects may influence trait variation. This will enable a deeper understanding of how genetic variants may regulate biological processes influencing sex-biased phenotypes.

Kynurenines, Gender and Neuroinflammation; Showcase Schizophrenia.

Schizophrenia has a clear sexual dimorphism in age of onset and progression. The underlying mechanisms of this dimorphism are not known, but may be found in the interactions of sex hormones with the tryptophan catabolising kynurenine pathway. Schizophrenia is associated with general inflammation and disruption of glutamatergic and dopaminergic signalling. Metabolites of the kynurenine pathway have been shown to be immunomodulatory and have effects on glutamatergic and dopaminergic signalling. This review discusses the currently available literature on sex hormones and their effect on the kynurenine pathway in the context of the glutamatergic, dopaminergic and immunological features of schizophrenia.

Acarbose, 17‐α‐estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males

Four agents — acarbose (ACA), 17-α-estradiol (EST), nordihydroguaiaretic acid (NDGA), and methylene blue (MB) — were evaluated for lifespan effects in genetically heterogeneous mice tested at three sites. Acarbose increased male median lifespan by 22% (P < 0.0001), but increased female median lifespan by only 5% (P = 0.01). This sexual dimorphism in ACA lifespan effect could not be explained by differences in effects on weight. Maximum lifespan (90th percentile) increased 11% (P < 0.001) in males and 9% (P = 0.001) in females. EST increased male median lifespan by 12% (P = 0.002), but did not lead to a significant effect on maximum lifespan. The benefits of EST were much stronger at one test site than at the other two and were not explained by effects on body weight. EST did not alter female lifespan. NDGA increased male median lifespan by 8–10% at three different doses, with P-values ranging from 0.04 to 0.005. Females did not show a lifespan benefit from NDGA, even at a dose that produced blood levels similar to those in males, which did show a strong lifespan benefit. MB did not alter median lifespan of males or females, but did produce a small, statistically significant (6%, P = 0.004) increase in female maximum lifespan. These results provide new pharmacological models for exploring processes that regulate the timing of aging and late-life diseases, and in particular for testing hypotheses about sexual dimorphism in aging and health.

Mitochondria, maternal inheritance, and asymmetric fitness: Why males die younger

Mitochondrial function is achieved through the cooperative interaction of two genomes: one nuclear (nuDNA) and the other mitochondrial (mtDNA). The unusual transmission of mtDNA, predominantly maternal without recombination is predicted to affect the fitness of male offspring. Recent research suggests the strong sexual dimorphism in aging is one such fitness consequence. The uniparental inheritance of mtDNA results in a selection asymmetry; mutations that affect only males will not respond to natural selection, imposing a male-specific mitochondrial mutation load. Prior work has implicated this male-specific mutation load in disease and infertility, but new data from fruit flies suggests a prominent role for mtDNA in aging; across many taxa males almost invariably live shorter lives than females. Here we discuss this new work and identify some areas of future research that might now be encouraged to explore what may be the underpinning cause of the strong sexual dimorphism in aging.

Mitochondria, Maternal Inheritance, and Male Aging

The maternal transmission of mitochondrial genomes invokes a sex-specific selective sieve, whereby mutations in mitochondrial DNA can only respond to selection acting directly on females. In theory, this enables male-harming mutations to accumulate in mitochondrial genomes when these same mutations are neutral, beneficial, or only slightly deleterious in their effects on females. Ultimately, this evolutionary process could result in the evolution of male-specific mitochondrial mutation loads; an idea previously termed Mother's Curse. Here, we present evidence that the effects of this process are broader than hitherto realized, and that it has resulted in mutation loads affecting patterns of aging in male, but not female Drosophila melanogaster. Furthermore, our results indicate that the mitochondrial mutation loads affecting male aging generally comprise numerous mutations over multiple sites. Our findings thus suggest that males are subject to dramatic consequences that result from the maternal transmission of mitochondrial genomes. They implicate the diminutive mitochondrial genome as a hotspot for mutations that affect sex-specific patterns of aging, thus promoting the idea that a sex-specific selective sieve in mitochondrial genome evolution is a contributing factor to sexual dimorphism in aging, commonly observed across species.

Sexual size dimorphism in the Tyrrhenian tree frog: a life‐history perspective

AbstractSexual size dimorphism (SSD) is often explained as the differential equilibrium between stabilizing survival selection and directional sexual/fecundity selection on the body size of males and females. Provided that survival selection is similar in both sexes, female‐biased SSD is thought to occur when fecundity selection on female body size is stronger than sexual selection on male body size. However, in animals with indeterminate growth, body size depends on several life‐history traits, thus, to understand why SSD has evolved, one should understand how it arises. We investigate SSD in the Tyrrhenian tree frog, Hyla sarda, by describing sexual dimorphism in age and growth and by assessing how body size affects their reproductive success. Females are 16% larger than males because they mature 1 year later, live 1 year longer and reach a larger asymptotic body size. Furthermore, body size correlates positively with female fecundity, but not with male mating success. These results suggest that SSD arises from differential optimal trade‐offs between the expected number of reproductive episodes (which decreases with prolonging growth) and the expected success in each reproductive episode (which increases with prolonging growth).

Pulse Pressure Inversely Correlates with Telomere Length in French Men

P126 Cardiovascular risk increases with chronological age. Pulse pressure (PP) also increases with chronological age and is an independent indicator of cardiovascular risk. It is therefore possible that after age-adjustment, the biological age of persons with wide PP is more advanced than their chronological age would indicate. We explored whether an index of biological age, namely telomere length (measured by the mean length of the terminal restriction fragment, TRF), provides a better account than chronological age of about variation in PP. We studied 193 French men and women (age 56 ± 11 years) on no antihypertensive medications. Univariate analysis showed that in both genders, TRF length (in WBCs) was correlated inversely with age (p&lt; 0.01). The rate of telomere attrition was 0.038 and 0.036 kb/year for men and women, respectively. Only in men, after adjustment for mean arterial pressure, TRF length accounted for 12% variability in PP (p&lt;0.001), while chronological age accounted for 10% variability in PP (p&lt;0.001). Age-adjusted TRF length was longer in women than men (8.67 ± 0.09 vs 8.38 ± 0.07 kb, p = 0.016). We conclude that TRF length adds additional information about variability in PP among men, such that men with shorter telomere length are more likely to exhibit a wider PP. The longer telomere length in women suggests that for a given chronological age, the biological age of men is more advanced than that of women. The results also underscore the sexual dimorphism in aging and blood pressure regulation. We propose that large-scale studies should be undertaken to explore the relation between telomere length and cardiovascular risk.

Isonymy in emigrants from Ferrara in 1981–1988

The distribution of surnames in the emigrants from the population of the town of Ferrara in the period 1981-88 was studied by sex and place of birth, namely Ferrara versus other places. Emigrants born in Ferrara were defined as first time emigrants and those who had previously immigrated to Ferrara were defined second time emigrants. It was found that random isonymy is smaller in second time emigrants. Sex ratio is not different in the two types of emigrants. As indicators of the abundance of surnames in a distribution, the common ecological indexes derived from entropy were used and compared between types of emigrants. It was found that redundancy, as isonymy, is larger in the first time emigrants than in second time emigrants. It was observed that second time emigrants were consistently and significantly older than first time emigrants, and that a considerable fraction of them, (22.4%) returned to their place of birth. A sexual dimorphism in age at emigration was observed in second time emigrants, females emigrating at an older age than males.