Biology subjects

Sexton, C. L.

Publications and source records attributed to Sexton, C. L..

5 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↗

bioRxiv2023

Early morning run-training results in enhanced endurance performance adaptations in mice.

Endurance performance exhibits time-of-day variation in both humans and rodents, peaking in the late active-phase. However, whether the timing of endurance training influences performance adaptations remains unclear. To investigate, female mice were trained 5-d/week for 6-weeks at either ZT13 or ZT22, using treadmill running at 70% of each animals maximal capacity. Endurance performance was assessed at baseline, week-3, and week-6. Secondary outcomes included blood glucose and lactate, cage activity, body composition, liver and skeletal muscle glycogen content, mitochondrial and contractile protein expression. At baseline, late-active phase (ZT22)-tested mice exhibited significantly higher endurance capacity than early-active phase (ZT13)-tested mice (P<0.05). Following 6 weeks of training, ZT13-trained mice demonstrated a greater rate of improvement, with endurance increasing by 132% (P<0.05), compared to 45% in afternoon ZT22-trained mice. By week 6, performance improved but was similar between groups (P>0.05), despite lower absolute training volumes in the ZT13 group. Both training groups reduced fat-mass (ZT13: -31%,ZT22: -32%; P<0.05 vs. control), with no differences in lean mass, food intake or muscle and liver glycogen content (P>0.05). In skeletal muscle, ZT13-trained mice were associated with increased (P<0.05) COXIV protein expression, citrate synthase activity, and shifts in MyHC isoform expression, without changes (P>0.05) in mitochondrial content. ZT13-training elicited superior performance adaptations despite lower absolute workloads, indicating enhanced training efficiency. These findings identify exercise timing as a biologically relevant factor influencing endurance adaptation and variability in exercise responses. NEW & NOTEWORTHYThis study demonstrates that endurance training in the early active phase induces greater performance adaptations than late active phase training in mice, resulting in overcoming diurnal differences in exercise performance, despite lower absolute training volumes. These findings reveal exercise timing influences training efficiency, likely via circadian regulation of skeletal muscle metabolism. This work identifies time-of-day as a biologically relevant and underappreciated variable contributing to the heterogeneity of exercise responses, even in tightly controlled preclinical models.

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↗

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↗