Biology subjects

Young, K. C.

Publications and source records attributed to Young, K. C..

7 recordsLinked to original sources

bioRxiv2025

Skeletal muscle mitochondrial responses to a single bout and six weeks of high load versus high volume resistance training in previously trained men

The effects of higher-load (HL) versus higher-volume (HV) resistance training (RT) on various molecular outcomes are similar. However, mitochondrial responses remain understudied. Therefore, the purpose of this study was to interrogate mitochondrial mRNA and protein responses to acute and chronic HL versus HV RT. Vastus lateralis biopsies from resistance trained males in two prior studies were assessed. In STUDY 1, 11 college-aged men completed an acute bout of either HL or HV RT exercises to failure. Biopsies were collected at PRE, 3 hours post-, and 6 hours post-exercise. In STUDY 2, 15 college-aged men participated in six weeks of supervised unilateral RT where each leg was assigned to either HL or HV RT. Biopsies were collected from both legs prior to and 72 hours following last training bout of the intervention. Biopsies from both studies were used to assess mitochondrial mRNAs, and STUDY 2 biopsies were assayed for mitochondrial proteins and CS activity. Results from both studies revealed several significant main effects of time but no significant interactions. Additionally, CS activity, a surrogate of mitochondrial content, decreased following chronic RT (p=0.016) but no interaction was observed between the HV and HL leg over time (p=0.882). In conclusion, while RT resulted in both acute mitochondrial mRNA as well as chronic CS activity and mitochondrial protein responses, there were no differences in the HL versus HV paradigms on these outcomes.

physiology↗

bioRxiv2025

Resistance training-induced appendicular lean tissue mass changes are largely unrelated to pre-training bone characteristics in a larger cohort of untrained adults

We sought to determine if pre-intervention bone characteristics measured by dual-energy x-ray absorptiometry (DXA) were associated with changes in bone-free lean tissue mass following a period of resistance training in a large cohort of untrained adults (n=119, 62M/57F, 26.0{+/-}4.7 kg/m2, age range = 18-70 years old). Participants completed 10-12 weeks of supervised whole-body resistance training twice weekly, and DXA scans were obtained approximately the same time of day prior to the intervention and 48-72 hours following the final training bout. Associations between baseline skeletal measures (e.g., appendicular bone characteristics, shoulder and hip widths) and training induced changes in appendicular lean mass were examined by estimating correlations between participant-level random slopes (reflecting change over time) and baseline skeletal measures. The same approach was used to evaluate associations between other participant attributes (e.g., age, training volume-load, self-reported energy intake) and appendicular lean tissue mass changes. Modeling was also used to explore whether baseline skeletal characteristics (e.g., shoulder and hip widths) moderated the change in appendicular lean tissue mass from training. All analyses used a Bayesian framework, and interpretation focused on estimated effect sizes and their associated credible intervals rather than formal null hypothesis testing. Strong positive associations were observed between pre-intervention characteristics including dual-arm lean tissue mass and dual-arm bone mineral content (r=0.90), dual-leg lean tissue mass and dual-leg bone mineral content (r=0.86), dual-leg lean tissue mass and pelvic mineral content (r=0.73), and dual-arm lean tissue mass and shoulder width (r=0.76). In contrast, weak associations were observed between training-induced changes in appendicular lean tissue mass versus bone characteristics, training volume-load, self-reported energy intake, self-reported protein intake, BMI, and age (-0.08[≤]r[≤] 0.24). After adjusting for sex, multivariable analyses indicated minimal evidence that skeletal characteristics moderated the hypertrophic response to training. These findings do not support a meaningful role of pre-training bone characteristics in influencing the lean tissue mass adaptations to shorter-term resistance training.

physiology↗

bioRxiv2023

Resistance Training Diminishes Mitochondrial Adaptations to Subsequent Endurance Training

We investigated the effects of performing a period of resistance training (RT) on the performance and molecular adaptations to a subsequent period of endurance training (ET). Twenty-five young adults were divided into RT+ET (n=13), which underwent seven weeks of RT followed by seven weeks of ET, and ET-only (n=12), which performed seven weeks of ET. Body composition, endurance performance, and muscle biopsies were collected before RT (T1, baseline for RT+ET), before ET (T2, post RT for RT+ET and baseline for ET), and after ET (T3). Immunohistochemistry was performed to determine fiber cross-sectional area (fCSA), myonuclear content, myonuclear domain size, satellite cell number, and mitochondrial content. Western blots were used to quantify markers of mitochondrial remodeling. Citrate synthase activity and markers of ribosome content were also investigated. Resistance training improved body composition and strength, increased vastus lateralis thickness, mixed and type II fCSA, myonuclear number, markers of ribosome content, and satellite cell content (p<0.050). In response to ET, both groups similarly decreased body fat percentage and improved endurance performance (e.g., VO2max, and speed at which the onset of blood lactate accumulation occurred during the VO2max test). Levels of mitochondrial complexes I-IV in the ET-only group increased 32-66%, while the RT+ET group increased 1-11%. Additionally, mixed fiber relative mitochondrial content increased 15% in the ET-only group but decreased 13% in the RT+ET group. In conclusion, RT performed prior to ET had no additional benefits to ET adaptations. Moreover, prior RT seemed to impair mitochondrial adaptations to ET. KEY POINTS SUMMARYO_LIResistance training is largely underappreciated as a method to improve endurance performance, despite reports showing it may improve mitochondrial function. C_LIO_LIAlthough several concurrent training studies are available, in this study we investigated the effects of performing a period resistance training on the performance and molecular adaptations to subsequent endurance training. C_LIO_LIPrior resistance training did not improve endurance performance and impaired most mitochondrial adaptations to subsequent endurance training, but that seemed to be a result of detraining from resistance training. C_LI

molecular biology↗

bioRxiv2022

Skeletal muscle DNA methylation and mRNA responses to a bout of higher versus lower load resistance exercise in previously trained men

We sought to determine the skeletal muscle genome-wide DNA methylation and mRNA responses to one bout of lower-load (LL) versus higher-load (HL) resistance exercise. Trained college-aged males (n=11, 23{+/-}4 years old, 4{+/-}3 years self-reported training) performed LL or HL bouts to failure separated by one week. The HL bout (i.e., 80 Fail) consisted of four sets of back squats and four sets of leg extensions to failure using 80% of participants estimated one-repetition maximum (i.e., est. 1-RM). The LL bout (i.e., 30 Fail) implemented the same paradigm with 30% of est. 1-RM. Vastus lateralis muscle biopsies were collected before, 3 hours, and 6 hours after each bout. Muscle DNA and RNA were batch-isolated and analyzed using the 850k Illumina MethylationEPIC array and Clariom S mRNA microarray, respectively. Performed repetitions were significantly greater during the 30 Fail versus 80 Fail (p<0.001), although total training volume (sets x reps x load) was not significantly different between bouts (p=0.571). Regardless of bout, more CpG site methylation changes were observed at 3-versus 6-hours post exercise (239,951 versus 12,419, respectively; p<0.01), and nuclear global ten-eleven translocation (TET) activity, but not global DNA methyltransferase activity, increased 3- and 6-hours following exercise regardless of bout. The percentage of genes significantly altered at the mRNA level that demonstrated opposite DNA methylation patterns was greater 3- versus 6-hours following exercise (~75% versus ~15%, respectively). Moreover, high percentages of genes that were up- or downregulated 6 hours following exercise also demonstrated significantly inversed DNA methylation patterns across one or more CpG sites 3 hours following exercise (65% and 82%, respectively). While 30 Fail decreased DNA methylation across various promoter regions versus 80 Fail, transcriptome-wide mRNA and bioinformatics indicated that gene expression signatures were largely similar between bouts. Bioinformatics overlay of DNA methylation and mRNA expression data indicated that genes related to "Focal adhesion", "MAPK signaling", and "PI3K-Akt signaling" were significantly affected at the 3- and 6-hour time points, and again this was regardless of bout. In conclusion, extensive molecular profiling suggests that post-exercise alterations in the skeletal muscle DNA methylome and mRNA transcriptome elicited by LL and HL training bouts to failure are largely similar, and this could be related to equal volumes performed between bouts.

molecular biology↗

bioRxiv2022

Single-nucleus RNA-seq reveals disrupted cell maturation by chorioamnionitis in the preterm cerebellum of nonhuman primates

Preterm birth is often associated with chorioamnionitis and increased risk of neurodevelopmental disorders. Preterm birth also leads to cerebellar underdevelopment but the mechanisms of disrupted cerebellar development in preterm infants are little understood. Here, we leveraged single-nuclei RNA-sequencing of the cerebellum in a rhesus macaque model of chorioamnionitis and preterm birth, to show that chorioamnionitis leads to Purkinje cell loss and disrupted maturation of granule cells and oligodendrocytes in the fetal cerebellum at late gestation. Purkinje cell loss is accompanied by decreased sonic hedgehog signaling from Purkinje cells to granule cells, which show an accelerated maturation. Chorioamnionitis also accelerated pre-oligodendrocyte maturation into myelinating oligodendrocytes, confirmed by increased expression of myelin basic protein in the cerebellum of chorioamnionitis-exposed fetuses. These findings are consistent with reported histopathological findings in individuals with autism and suggest a novel mechanism through which perinatal inflammation contributes to neurodevelopmental disorders.

neuroscience↗

bioRxiv2021

Laryngeal and swallow dysregulation following acute cervical spinal cord injury

Proper function of the larynx is vital to airway protection, including swallow. While the swallow reflex is controlled by the brainstem, patients with cervical spinal cord injuries (cSCI) are likely at increased risk of disordered swallow (dysphagia) and pneumonia, and the underlying mechanisms are unknown. We aimed to determine if acute spinal cord injury would disrupt swallow function in animal models. We hypothesized that 1) loss of descending efferent information to the diaphragm would affect swallow and breathing differently, and that 2) loss of ascending spinal afferent information would alter central swallow regulation to change motor drive to the upper airway. We recorded amplitudes of laryngeal and inspiratory muscle electromyograms (EMGs), submental and pharyngeal muscle EMGs, and cardiorespiratory measures in freely breathing pentobarbital-anesthetized cats and rats. First, we assessed the effect of a lateral hemisection at the second cervical level (C2) in cats during breathing. Posterior cricoarytenoid (laryngeal abductor) EMG activity during inspiration increased nearly two-fold, indicating that inspiratory laryngeal drive increased following cSCI. Ipsilateral to the injury, the crural diaphragm EMG was significantly reduced during breathing (62 {+/-} 25 percent change post-injury), but no animal had a complete termination of all activity; 75% of animals had an increase in contralateral diaphragm recruitment after cSCI, but this did not reach significance. Next, we assessed the effect of C2 lateral hemisection in cats during swallow. The thyroarytenoid (laryngeal adductor) and thyropharyngeus (pharyngeal constrictor) both increased EMG activity during swallow, indicating increased upper airway drive during swallow following cSCI. There was no change in the number of swallows stimulated per trial. We also found that diaphragm activity during swallow (schluckatmung) was bilaterally suppressed after lateral C2 hemisection, which was unexpected because this injury did not suppress contralateral diaphragm activity during breathing. Swallow-breathing coordination was also affected by cSCI, with more post-injury swallows occurring during early expiration. Finally, because we wanted to determine if the chest wall is a major source of feedback for laryngeal regulation, we performed T1 total transections in rats. As in the cat C2 lateral hemisection, a similar increase in inspiratory laryngeal activity (posterior cricoarytenoid) was the first feature noted after rat T1 complete spinal cord transection. In contrast to the cat C2 lateral hemisection, diaphragmatic respiratory drive increased after T1 transection in every rat (215 {+/-} 63 percent change), and this effect was significant. Overall, we found that spinal cord injury alters laryngeal drive during swallow and breathing, and alters swallow-related diaphragm activity. Our results show behavior-specific effects, suggesting that swallow may be more affected than breathing is by cSCI, and emphasizing the need for additional studies on laryngeal function during breathing and swallow after spinal cord injury.

neuroscience↗

bioRxiv2021

Resistance training rejuvenates the mitochondrial methylome in aged human skeletal muscle

Resistance training (RT) alters skeletal muscle nuclear DNA methylation patterns (or the methylome). However, no study has examined if RT affects the mitochondrial DNA (mtDNA) methylome. Herein, ten older untrained males (65{+/-}7 years old) performed six weeks of full-body RT (twice weekly). Body composition and knee extensor torque were assessed prior to and 72 hours following the last RT session. Vastus lateralis (VL) biopsies were also obtained. VL DNA was subjected to reduced representation bisulfite sequencing providing excellent coverage across the ~16-kilobase mtDNA methylome (254 CpG sites). Various biochemical assays were also performed, and older male data were compared to younger trained males (22{+/-}2 years old, n=7). RT increased whole-body lean tissue mass (p=0.017), VL thickness (p=0.012), and knee extensor torque (p=0.029) in older males. RT also profoundly affected the mtDNA methylome in older males, as 63% (159/254) of the CpG sites demonstrated reduced methylation (p<0.05). Notably, several mtDNA sites presented a more "youthful" signature after RT in older males when comparisons were made to younger males. The 1.12 kilobase D-loop/control region on mtDNA, which regulates mtDNA replication and transcription, possessed enriched hypomethylation in older males following RT. Enhanced expression of mitochondrial H- and L-strand genes and increases in mitochondrial complex III and IV protein levels were also observed (p<0.05). This is the first study to show RT alters the mtDNA methylome in skeletal muscle. Observed methylome alterations may enhance mitochondrial transcription, and RT remarkably evokes mitochondrial methylome profiles to mimic a more youthful signature in older males.

molecular biology↗