Toward a Robust Definition of Sport Sex

Endocrine Reviews, Год журнала: 2024, Номер 45(5), С. 709 - 736

Опубликована: Апрель 5, 2024

Abstract Elite individual sports in which success depends on power, speed, or endurance are conventionally divided into male and female events using traditional binary definitions of sex. Male puberty creates durable physical advantages due to the 20- 30-fold increase circulating testosterone producing a sustained uplift men's muscle, bone, hemoglobin, cardiorespiratory function resulting from during lives. These provide strong justification for separate protected category allowing women achieve fame fortune they would be denied if competing against men. Recent wider social acceptance transgender individuals, together with less recognized involvement intersex challenge threaten defeat sex classifications elite events. This can create unfair seeking inclusion unmodified male-bodied athletes gender identity who have gained puberty. Based reproductive physiology, this paper proposes working definition sport based primarily an individual's experience applied various XY conditions. Consistent multidimensionality biological (chromosomal, genetic, hormonal, anatomical sex), may viewed as multistrand cable whose overall strength survives when any single strand weakens fails, rather than unidimensional chain is only good its weakest link.

Язык: Английский

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A conserved complex lipid signature marks human muscle aging and responds to short-term exercise

Nature Aging, Год журнала: 2024, Номер 4(5), С. 681 - 693

Опубликована: Апрель 12, 2024

Язык: Английский

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SMURF1-Induced Ubiquitination of FTH1 Disrupts Iron Homeostasis and Suppresses Myogenesis

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(3), С. 1390 - 1390

Опубликована: Фев. 6, 2025

Ferritin heavy chain 1 (FTH1) is pivotal in the storage, release, and utilization of iron, plays a crucial role ferroptosis pathway, exerts significant impacts on various diseases. Iron influences skeletal muscle development health by promoting cell growth, ensuring energy metabolism ATP synthesis, maintaining oxygen supply, facilitating protein synthesis. However, precise molecular mechanisms underlying iron’s regulation growth remain elusive. In this study, we demonstrated that conditional knockout (cKO) FTH1 results atrophy impaired exercise endurance. vitro studies using cKO myoblasts revealed notable decreases GSH concentrations, elevated levels lipid peroxidation, substantial accumulation Fe2+, collectively implying induction ferroptosis. Mechanistically, E3 ubiquitin-protein ligase SMURF1 (SMURF1) acts as an ubiquitin for FTH1, thereby ubiquitination subsequent degradation FTH1. Consequently, activation pathway impedes myoblast differentiation into myotubes. This study identifies novel regulator development, implicating its potential significance through iron homeostasis.

Язык: Английский

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Sex differences in endurance exercise capacity and skeletal muscle lipid metabolism in mice

Physiological Reports, Год журнала: 2022, Номер 10(3)

Опубликована: Фев. 1, 2022

Previous studies suggest that sex differences in lipid metabolism exist with females demonstrating a higher utilization of lipids during exercise, which is mediated partly by increased muscle triglycerides. However, whether these changes contribute directly to endurance exercise performance unclear. Therefore, the objective this study was investigate contribution substrate capacity (EEC) mice. Male and female C57BL/6-NCrl mice were subjected an EEC test until exhaustion on motorized treadmill. The treadmill set at 10% incline, speed gradually from 10.2 m/min 22.2 fixed intervals for up 2.5 h. Tissues blood harvested immediately following EEC. A cohort sedentary, non-exercised male used as controls. Females outperformed males ~25% Serum levels both fatty acids ketone bodies ~50% end In sedentary mice, skeletal triglyceride content significantly greater compared males. Gene expression analysis demonstrated genes involved acid oxidation no associated glucose uptake or body oxidation. findings have ability mobilize utilize energy.

Язык: Английский

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Age‐related changes of skeletal muscle metabolic response to contraction are also sex‐dependent

The Journal of Physiology, Год журнала: 2023, Номер 603(1), С. 69 - 86

Опубликована: Сен. 23, 2023

Abstract Mitochondria adapt to increased energy demands during muscle contraction by acutely altering metabolite fluxes and substrate oxidation. With age, an impaired mitochondrial metabolic response may contribute reduced exercise tolerance decreased skeletal mass, specific force, overall fatty depositions in the muscle, frailty depressed maintenance. We hypothesized that elevated stress mitochondria with age alters capacity of utilize different substrates following contraction. To test this hypothesis, we used vivo electrical stimulation simulate high‐intensity intervals (HII) or low intensity steady‐state (LISS) young (5–7 months) aged (27–29 male female mice characterize effects sex on utilization Mitochondrial respiration using glutamate males HII oxidation was inhibited both contracted non‐stimulated muscle. Analyses metabolome indicated changes pathways induced LISS contractions are absent improved function HII, treated females elamipretide (ELAM), a mitochondrially‐targeted peptide shown improve bioenergetics restore redox status ELAM removed inhibition showed pathway suggesting rescuing improving bioenergetic from increases enhances image Key points Acute local gastrocnemius can systemically alter Age‐related palmitoyl carnitine sex‐dependent. Respiration after is Metabolite level decrease mice. Treatment partially rescue

Язык: Английский

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Sirt2 Regulates Liver Metabolism in a Sex-Specific Manner

Biomolecules, Год журнала: 2024, Номер 14(9), С. 1160 - 1160

Опубликована: Сен. 15, 2024

Sirtuin-2 (Sirt2), an NAD+-dependent lysine deacylase enzyme, has previously been implicated as a regulator of glucose metabolism, but the specific mechanisms remain poorly defined. Here, we observed that Sirt2−/− males, not females, have decreased body fat, moderate hypoglycemia upon fasting, and perturbed handling during exercise compared to wild type controls. Conversion injected lactate, pyruvate, glycerol boluses into via gluconeogenesis was impaired, only in males. Primary male hepatocytes exhibited reduced glycolysis mitochondrial respiration. RNAseq proteomics were used interrogate behind this liver phenotype. Loss Sirt2 did lead transcriptional dysregulation, very few genes altered transcriptome. In keeping with this, there also negligible changes protein abundance. Site-specific quantification hepatic acetylome, however, showed 13% all detected acetylated peptides significantly increased versus type, representing putative target sites. Strikingly, none these sites hyperacetylated female liver. The distributed across mitochondria (44%), cytoplasm (32%), nucleus (8%), other compartments (16%). Despite high number targets, antigen purified mitochondria, suggesting Sirt2’s regulation function occurs from outside organelle. We conclude regulates acetylation metabolism sex-specific manner.

Язык: Английский

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Effects of defined voluntary running distances coupled with high‐fat diet consumption on the skeletal muscle transcriptome of male mice

Physiological Reports, Год журнала: 2025, Номер 13(2)

Опубликована: Янв. 1, 2025

Abstract Exercise counters many adverse health effects of consuming a high‐fat diet (HFD). However, complex molecular changes that occur in skeletal muscle response to exercising while HFD are not yet known. We investigated the interplay between diverse exercise regimes and consumption on adaptation transcriptome. C57BL/6 male mice were randomized into five groups—one sedentary control group four groups. The groups consisted an unrestricted running (8.3 km/day) three restricted 75%, 50%, or 25% (6.3, 4.2, 2.1 km/day, respectively). Total RNA was extracted from frozen gastrocnemius for transcriptome analyses. DEG counts 1347, 1823, 1103, 1107 there 107, 169, 67, 89 unique genes present HFD‐25%, HFD‐50%, HFD‐75%, HFD‐U, respectively. Comparing groups, we found at 50% resulted most differentially expressed transcripts with MAPK PPAR signaling pathways enriched down‐ up‐regulated genes, These results demonstrate distance impacts suggest middle‐distance may provide greatest protection against diet‐induced stress coupled exercise.

Язык: Английский

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The influence of sex on activity in voluntary wheel running, forced treadmill running, and open field testing in mice

Physiological Reports, Год журнала: 2025, Номер 13(4)

Опубликована: Фев. 1, 2025

Abstract Physical activity is commonly used for both measuring and treating dysfunction. While preclinical work has been historically biased towards males, the inclusion of males females gaining popularity. With increasing sexes, it imperative to determine sex differences in common behavioral assays. This was a secondary analysis healthy naïve mice baseline three assays: voluntary wheel running (32 mice), forced treadmill (178 open field (88 mice). In running, showed greater distance run, time, bout duration, speed, but no difference total bouts. time exhaustion, maximum speed attained. field, active over 30 min; however, male downward trajectory final 20 min testing, whereas did not. These data suggest that demonstrate comparable intensity female do not match females' duration activity, especially volitional tasks. Researchers utilizing these assays should account as they could mask true findings an experiment.

Язык: Английский

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Atf3 controls transitioning in female mitochondrial cardiomyopathy as identified by spatial and single-cell transcriptomics

Science Advances, Год журнала: 2025, Номер 11(14)

Опубликована: Апрель 4, 2025

Oxidative phosphorylation defects result in now intractable mitochondrial diseases (MD) with cardiac involvement markedly affecting prognosis. The mechanisms underlying the transition from compensation to dysfunction response metabolic deficiency remain unclear. Here, we used spatially resolved transcriptomics and single-nucleus RNA sequencing (snRNA-seq) on heart of a patient cardiomyopathy (MCM), combined an MCM mouse model cardiac-specific Ndufs6 knockdown (FS6KD). Cardiomyocytes demonstrated most heterogeneous expression landscape among cell types caused by perturbation, pseudotime trajectory analysis revealed dynamic cellular states transitioning severe compromise. This progression coincided transient up-regulation transcription factor, ATF3 . Genetic ablation Atf3 FS6KD corroborated its pivotal role, effectively delaying female-specific manner. Our findings highlight fate-determining role female that latest transcriptomic will help decipher MD progression.

Язык: Английский

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Sex differences in ketogenic diet: are men more likely than women to lose weight?

Frontiers in Nutrition, Год журнала: 2025, Номер 12

Опубликована: Июнь 4, 2025

As economy is growing, the number of patients living with obesity has rapidly increased globally. Patients or diabetes have become a serious global health issue that requires attention and participation society as whole. The ketogenic diet, an emerging nutritional therapy for improving obesity, takes into consideration differences between sexes in genetic variation, hormonal balance, body fat distribution. aim to elucidate effectiveness sex dieting weight loss explore suitable strategies. In this review, we delve physiological sexual men women terms muscle tissue discuss sex-specific potential mechanisms underlying differential effects diet loss. Based on foundation, further propose brief recommendations beneficial both women. It hoped that, direction, optimization short-term long-term clinical programs can be developed based sexes.

Язык: Английский

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