Evolutionary optimality in sex differences of longevity and athletic performances.
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ABSTRACT:
SUBMITTER: Asanuma H
PROVIDER: S-EPMC4067624 | biostudies-other | 2014
REPOSITORIES: biostudies-other
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Project description:ImportanceSex differences in genetic associations with human longevity remain largely unknown; investigations on this topic are important for individualized health care.ObjectiveTo explore sex differences in genetic associations with longevity.Design setting and participantsThis population-based case-control study used sex-specific genome-wide association study and polygenic risk score (PRS) analyses to examine sex differences in genetic associations with longevity. Five hundred sixty-four male and 1614 female participants older than 100 years were compared with a control group of 773 male and 1526 female individuals aged 40 to 64 years. All were Chinese Longitudinal Healthy Longevity Study participants with Han ethnicity who were recruited in 1998 and 2008 to 2014.Main outcomes and measuresSex-specific loci and pathways associated with longevity and PRS measures of joint effects of sex-specific loci.ResultsEleven male-specific and 11 female-specific longevity loci (P < 10-5) and 35 male-specific and 25 female-specific longevity loci (10-5 ≤ P < 10-4) were identified. Each of these loci's associations with longevity were replicated in north and south regions of China in one sex but were not significant in the other sex (P = .13-.97), and loci-sex interaction effects were significant (P < .05). The associations of loci rs60210535 of the LINC00871 gene with longevity were replicated in Chinese women (P = 9.0 × 10-5) and US women (P = 4.6 × 10-5) but not significant in Chinese and US men. The associations of the loci rs2622624 of the ABCG2 gene were replicated in Chinese women (P = 6.8 × 10-5) and European women (P = .003) but not significant in both Chinese and European men. Eleven male-specific pathways (inflammation and immunity genes) and 34 female-specific pathways (tryptophan metabolism and PGC-1α induced) were significantly associated with longevity (P < .005; false discovery rate < 0.05). The PRS analyses demonstrated that sex-specific associations with longevity of the 4 exclusive groups of 11 male-specific and 11 female-specific loci (P < 10-5) and 35 male-specific and 25 female-specific loci (10-5 ≤P < 10-4) were jointly replicated across north and south discovery and target samples. Analyses using the combined data set of north and south showed that these 4 groups of sex-specific loci were jointly and significantly associated with longevity in one sex (P = 2.9 × 10-70 to 1.3 × 10-39) but not jointly significant in the other sex (P = .11 to .70), while interaction effects between PRS and sex were significant (P = 4.8 × 10-50 to 1.2 × 10-16).Conclusion and relevanceThe sex differences in genetic associations with longevity are remarkable, but have been overlooked by previously published genome-wide association studies on longevity. This study contributes to filling this research gap and provides a scientific basis for further investigating effects of sex-specific genetic variants and their interactions with environment on healthy aging, which may substantially contribute to more effective and targeted individualized health care for male and female elderly individuals.
| S-EPMC6173523 | biostudies-literature
Project description:Elite athletic competitions have separate male and female events due to men's physical advantages in strength, speed, and endurance so that a protected female category with objective entry criteria is required. Prior to puberty, there is no sex difference in circulating testosterone concentrations or athletic performance, but from puberty onward a clear sex difference in athletic performance emerges as circulating testosterone concentrations rise in men because testes produce 30 times more testosterone than before puberty with circulating testosterone exceeding 15-fold that of women at any age. There is a wide sex difference in circulating testosterone concentrations and a reproducible dose-response relationship between circulating testosterone and muscle mass and strength as well as circulating hemoglobin in both men and women. These dichotomies largely account for the sex differences in muscle mass and strength and circulating hemoglobin levels that result in at least an 8% to 12% ergogenic advantage in men. Suppression of elevated circulating testosterone of hyperandrogenic athletes results in negative effects on performance, which are reversed when suppression ceases. Based on the nonoverlapping, bimodal distribution of circulating testosterone concentration (measured by liquid chromatography-mass spectrometry)-and making an allowance for women with mild hyperandrogenism, notably women with polycystic ovary syndrome (who are overrepresented in elite athletics)-the appropriate eligibility criterion for female athletic events should be a circulating testosterone of <5.0 nmol/L. This would include all women other than those with untreated hyperandrogenic disorders of sexual development and noncompliant male-to-female transgender as well as testosterone-treated female-to-male transgender or androgen dopers.
| S-EPMC6391653 | biostudies-literature
Project description:To move closer to understanding the mechanistic underpinnings of sex differences in human longevity, we studied pet dogs to determine whether lifetime duration of ovary exposure was associated with exceptional longevity. This hypothesis was tested by collecting and analyzing lifetime medical histories, age at death, and cause of death for a cohort of canine 'centenarians'--exceptionally long-lived Rottweiler dogs that lived more than 30% longer than average life expectancy for the breed. Sex and lifetime ovary exposure in the oldest-old Rottweilers (age at death, > or = 13 years) were compared to a cohort of Rottweilers that had usual longevity (age at death, 8.0-10.8 years). Like women, female dogs were more likely than males to achieve exceptional longevity (OR, 95% CI = 2.0, 1.2-3.3; P = 0.006). However, removal of ovaries during the first 4 years of life erased the female survival advantage. In females, a strong positive association between ovaries and longevity persisted in multivariate analysis that considered other factors, such as height, body weight, and mother with exceptional longevity. A beneficial effect of ovaries on longevity in females could not be attributed to resistance against a particular disease or major cause of death. Our results document in dogs a female sex advantage for achieving exceptional longevity and show that lifetime ovary exposure, a factor not previously evaluated in women, is associated with exceptional longevity. This work introduces a conceptual framework for designing additional studies in pet dogs to define the ovary-sensitive biological processes that promote healthy human longevity.
| S-EPMC2805875 | biostudies-other
Project description:Sex differences in aging manifest in disparities in disease prevalence, physical health, and lifespan, where women tend to have greater longevity relative to men. However, in the Mediterranean Blue Zones of Sardinia (Italy) and Ikaria (Greece) are regions of centenarian abundance, male-female centenarian ratios are approximately one, diverging from the typical trend and making these useful regions in which to study sex differences of the oldest old. Additionally, these regions can be investigated as examples of healthy aging relative to other populations. DNA methylation (DNAm)-based predictors have been developed to assess various health biomarkers, including biological age, Pace of Aging, serum interleukin-6 (IL-6), and telomere length. Epigenetic clocks are biological age predictors whose deviation from chronological age has been indicative of relative health differences between individuals, making these useful tools for interrogating these differences in aging. We assessed sex differences between the Horvath, Hannum, GrimAge, PhenoAge, Skin and Blood, and Pace of Aging predictors from individuals in two Mediterranean Blue Zones and found that men displayed positive epigenetic age acceleration (EAA) compared to women according to all clocks, with significantly greater rates according to GrimAge (β = 3.55; p = 1.22 × 10-12), Horvath (β = 1.07; p = 0.00378) and the Pace of Aging (β = 0.0344; p = 1.77 × 10-08). Other DNAm-based biomarkers findings indicated that men had lower DNAm-predicted serum IL-6 scores (β = -0.00301, p = 2.84 × 10-12), while women displayed higher DNAm-predicted proportions of regulatory T cells than men from the Blue Zone (p = 0.0150, 95% Confidence Interval [0.00131, 0.0117], Cohen's d = 0.517). All clocks showed better correlations with chronological age in women from the Blue Zones than men, but all clocks showed large mean absolute errors (MAE >30 years) in both sexes, except for PhenoAge (MAE <5 years). Thus, despite their equal survival to older ages in these Mediterranean Blue Zones, men in these regions remain biologically older by most measured DNAm-derived metrics than women, with the exception of the IL-6 score and proportion of regulatory T cells.
| S-EPMC9726738 | biostudies-literature
Project description:While sex chromosomes carry sex-determining genes, they also often differ from autosomes in size and composition, consisting mainly of silenced heterochromatic repetitive DNA. Even though Y chromosomes show structural heteromorphism, the functional significance of such differences remains elusive. Correlative studies suggest that the amount of Y chromosome heterochromatin might be responsible for several male-specific traits, including sex-specific differences in longevity observed across a wide spectrum of species, including humans. However, experimental models to test this hypothesis have been lacking. Here we use the Drosophila melanogaster Y chromosome to investigate the relevance of sex chromosome heterochromatin in somatic organs in vivo. Using CRISPR-Cas9, we generated a library of Y chromosomes with variable levels of heterochromatin. We show that these different Y chromosomes can disrupt gene silencing in trans, on other chromosomes, by sequestering core components of the heterochromatin machinery. This effect is positively correlated to the level of Y heterochromatin. However, we also find that the ability of the Y chromosome to affect genome-wide heterochromatin does not generate physiological sex differences, including sexual dimorphism in longevity. Instead, we discovered that it is the phenotypic sex, female or male, that controls sex-specific differences in lifespan, rather than the presence of a Y chromosome. Altogether, our findings dismiss the 'toxic Y' hypothesis that postulates that the Y chromosome leads to reduced lifespan in XY individuals.
| S-EPMC10406604 | biostudies-literature
Project description:The COVID-19 pandemic has caused a global societal, economic, and social upheaval unseen in living memory. There have been substantial cross-national differences in the kinds of policies implemented by political decision-makers to prevent the spread of the virus, to test the population, and to manage infected patients. Among other factors, these policies vary with politicians' sex: early findings indicate that, on average, female leaders seem more focused on minimizing direct human suffering caused by the SARS-CoV-2 virus, while male leaders implement riskier short-term decisions, possibly aiming to minimize economic disruptions. These sex differences are consistent with broader findings in psychology, reflecting women's stronger empathy, higher pathogen disgust, health concern, care-taking orientation, and dislike for the suffering of other people-as well as men's higher risk-taking, Machiavellianism, psychopathy, narcissism, and focus on financial indicators of success and status. This review article contextualizes sex differences in pandemic leadership in an evolutionary framework. Evolution by natural selection is the only known process in nature that organizes organisms into higher degrees of functional order, or counteracts the unavoidable disorder that would otherwise ensue, and is therefore essential for explaining the origins of human sex differences. Differential sexual selection and parental investment between males and females, together with the sexual differentiation of the mammalian brain, drive sex differences in cognition and behavioral dispositions, underlying men's and women's leadership styles and decision-making during a global pandemic. According to the sexually dimorphic leadership specialization hypothesis, general psychobehavioral sex differences have been exapted during human evolution to create sexually dimorphic leadership styles. They may be facultatively co-opted by societies and/or followers when facing different kinds of ecological and/or sociopolitical threats, such as disease outbreaks or intergroup aggression. Early evidence indicates that against the invisible viral foe that can bring nations to their knees, the strategic circumspection of empathic feminine health "worriers" may bring more effective and humanitarian outcomes than the devil-may-care incaution of masculine risk-taking "warriors".
| S-EPMC8015803 | biostudies-literature
Project description:To evaluate the role of fluid and Na+ balance in the development of exercise-associated hyponatremia (EAH), changes in serum Na+ concentrations ([Na+]) and in body weight were analyzed in 2,135 athletes in endurance events. Eighty-nine percent of athletes completed these events either euhydrated (39%) or with weight loss (50%) and with normal (80%) or elevated (13%) serum [Na+]. Of 231 (11%) athletes who gained weight during exercise, 70% were normonatremic or hypernatremic, 19% had a serum [Na+] between 129-135 mmol/liter, and 11% a serum [Na+] of <129 mmol/liter. Serum [Na+] after racing was a linear function with a negative slope of the body weight change during exercise. The final serum [Na+] in a subset of 18 subjects was predicted from the amount of Na+ that remained osmotically inactive at the completion of the trial. Weight gain consequent to excessive fluid consumption was the principal cause of a reduced serum [Na+] after exercise, yet most (70%) subjects who gained weight maintained or increased serum [Na+], requiring the addition of significant amounts of Na+ (>500 mmol) into an expanded volume of total body water. This Na+ likely originated from osmotically inactive, exchangeable stores. Thus, EAH occurs in athletes who (i) drink to excess during exercise, (ii) retain excess fluid because of inadequate suppression of antidiuretic hormone secretion, and (iii) osmotically inactivate circulating Na+ or fail to mobilize osmotically inactive sodium from internal stores. EAH can be prevented by insuring that athletes do not drink to excess during exercise, which has been known since 1985.
| S-EPMC1311740 | biostudies-literature
Project description:When organisms need to perform multiple tasks they face a fundamental tradeoff: no phenotype can be optimal at all tasks. This situation was recently analyzed using Pareto optimality, showing that tradeoffs between tasks lead to phenotypes distributed on low dimensional polygons in trait space. The vertices of these polygons are archetypes--phenotypes optimal at a single task. This theory was applied to examples from animal morphology and gene expression. Here we ask whether Pareto optimality theory can apply to life history traits, which include longevity, fecundity and mass. To comprehensively explore the geometry of life history trait space, we analyze a dataset of life history traits of 2105 endothermic species. We find that, to a first approximation, life history traits fall on a triangle in log-mass log-longevity space. The vertices of the triangle suggest three archetypal strategies, exemplified by bats, shrews and whales, with specialists near the vertices and generalists in the middle of the triangle. To a second approximation, the data lies in a tetrahedron, whose extra vertex above the mass-longevity triangle suggests a fourth strategy related to carnivory. Each animal species can thus be placed in a coordinate system according to its distance from the archetypes, which may be useful for genome-scale comparative studies of mammalian aging and other biological aspects. We further demonstrate that Pareto optimality can explain a range of previous studies which found animal and plant phenotypes which lie in triangles in trait space. This study demonstrates the applicability of multi-objective optimization principles to understand life history traits and to infer archetypal strategies that suggest why some mammalian species live much longer than others of similar mass.
| S-EPMC4605829 | biostudies-literature
Project description:The choice of codons can influence local translation kinetics during protein synthesis. Whether codon preference is linked to cotranslational regulation of polypeptide folding remains unclear. Here, we derive a revised translational efficiency scale that incorporates the competition between tRNA supply and demand. Applying this scale to ten closely related yeast species, we uncover the evolutionary conservation of codon optimality in eukaryotes. This analysis reveals universal patterns of conserved optimal and nonoptimal codons, often in clusters, which associate with the secondary structure of the translated polypeptides independent of the levels of expression. Our analysis suggests an evolved function for codon optimality in regulating the rhythm of elongation to facilitate cotranslational polypeptide folding, beyond its previously proposed role of adapting to the cost of expression. These findings establish how mRNA sequences are generally under selection to optimize the cotranslational folding of corresponding polypeptides.
| S-EPMC3565066 | biostudies-literature
Project description:Purpose: To analyze sex and age group differences in strength, jump, speed, flexibility, and endurance performances of TeamGym athletes. Methods: A total of 91 Swedish elite gymnasts (junior female, n = 26, age = 15.4 y; senior female, n = 23, age = 20.0 y; junior male, n = 19, age = 15.6 y; senior male, n = 23, age = 20.6 y) participated in three testing sessions on three separate days. These were: (1) a series of flexibility tests for the lower- and upper-body; (2) strength tests for the lower- and upper-body; and (3) various types of jumps, a 20-m sprint-run, and a 3,000-m run test. Results: Males were 24% stronger in the back squat one-repetition maximum (relative to body mass) compared to females (P < 0.001, H g = 1.35). In the pull-ups and dips, 2.4 and 2.3 times more repetitions were completed by the males compared to the females (both P < 0.001, 0.70 ≤ R ≤ 0.77). However, females were similarly strong as males in the hanging sit-ups test (P = 0.724). The males jumped 29, 34, 33, and 17% higher in the squat jump (SJ), countermovement jump (CMJ), countermovement jump with arm swing (CMJa), and drop jump (DJ), respectively, compared to the females (all P ≤ 0.002, 0.14 ≤ ηp2 ≤ 0.60). In the 20-m sprint run, males were 4% faster than females (P < 0.001, R = 0.40). Moreover, the females had significantly better flexibility than the males in the trunk forward bending, front split, and side split tests (all P < 0.001, 0.24 ≤ ηp2 ≤ 0.54). In the 3,000-m run test, males were 11% faster than females (P < 0.001, ηp2 ≤ 0.54). Compared to junior athletes, seniors performed better in the pull-ups, dips, SJ, CMJ, CMJa, and 20-m sprint-run tests (all P ≤ 0.012, 0.31 ≤ R ≤ 0.56, 0.16 ≤ ηp2 ≤ 0.25), with separate within-sex age-group differences (i.e., juniors vs. seniors) that were significant for the males but not for the females in the SJ, CMJ, CMJa, and 20-m sprint-run tests (males: all P < 0.001, 0.67 ≤ R ≤ 0.69, 1.37 ≤ H g ≤ 2.01; females: all P = 0.298-732). Conclusions: Large sex and age-group differences were observed for most physical performance metrics with specific within-sex age-group differences only observed for male athletes, with male seniors performing better than juniors in the SJ, CMJ, CMJa, and 20-m sprint-run tests.
| S-EPMC8158296 | biostudies-literature