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This is the first study, to our knowledge, to examine myofiber hypertrophy from low-load resistance training with blood flow restriction (BFR) in females. Although this type of training did not result in myofiber hypertrophy, there were comparable increases in muscle cross-sectional area compared with high-load resistance training. These findings possibly highlight that males and females respond in a similar manner to high-load resistance training and low-load resistance training with BFR.

Herein, we determined if a multi-ingredient supplement (NAD3; 312 mg of combined Wasabia japonica extract, theacrine, and copper (I)niacin chelate) versus a placebo (CTL) affected peripheral blood mononuclear (PMBC) transcriptomic, DNA methylation, and sirtuin activity profiles in middle-aged adults after 12 weeks of supplementation. Several mRNAs demonstrated interactions (n = 148 at ±1.5-fold change, p < 0.01), and more stringent filtering indicated that 25 mRNAs were upregulated and 29 were downregulated in the NAD3 versus CTL group. Bioinformatics on these 64 mRNAs suggested that DNA conformational alterations may have been promoted with NAD3 supplementation, and this was corroborated with more CpG sites being hypermethylated (p < 0.001) in the CTL versus the NAD3 group when examining pre- to post-intervention changes (369 versus 35). PBMC SIRT activity decreased in CTL participants (p < 0.001), but not in NAD3 participants (p = 0.289), and values at 12 weeks trended higher in NAD3 participants (p = 0.057). Interestingly, the pre- to post- changes in SIRT activity values significantly correlated with changes in PBMC NAD+: NADH values obtained from a previous investigation in these participants (r = 0.534, p = 0.015). In conclusion, the current mRNA and DNA methylation data indirectly suggest that NAD3 supplementation may affect PBMC DNA conformation, while other direct assays suggest that NAD3 supplementation maintains SIRT activity through the potential maintenance of NAD+: NADH levels. However, these results are preliminary due to limited n-sizes and the study being performed in middle-aged adults.

Retrotransposons are gene segments that proliferate in the genome, and the Long INterspersed Element 1 (LINE-1 or L1) retrotransposon is active in humans. Although older mammals show enhanced skeletal muscle L1 expression, exercise generally reverses this trend. We hypothesize skeletal muscle L1 expression influences muscle physiology, and additional innovative investigations are needed to confirm this hypothesis.

This study continues to delineate muscle biology differences between lower and higher responders to resistance training and is unique in that a female population was interrogated. As has been reported in prior studies, increases in satellite cell numbers are related to positive responses to resistance training. Satellite cell responsivity, rather than changes in muscle ribosome content per milligrams of tissue, may be a more important factor in delineating resistance-training responses in women.

Although past studies have examined aspects of extracellular matrix remodeling in relation to mechanical overload or resistance training, this study serves to expand our knowledge on a multitude of extracellular matrix markers and whether these markers adapt to resistance training or are associated with differential hypertrophic responses.

What is the central question of this study? Do changes in myofibre cross-sectional area, pennation angle and fascicle length predict vastus lateralis whole-muscle cross-sectional area changes following resistance training? What is the main finding and its importance? Changes in vastus lateralis mean myofibre cross-sectional area, fascicle length and pennation angle following a period of resistance training did not collectively predict changes in whole-muscle cross-sectional area. Despite the limited sample size in this study, these data reiterate that it remains difficult to generalize the morphological adaptations that predominantly drive tissue-level vastus lateralis muscle hypertrophy.Myofibre hypertrophy during resistance training (RT) poorly associates with tissue-level surrogates of hypertrophy. However, it is underappreciated that, in pennate muscle, changes in myofibre cross-sectional area (fCSA), fascicle length (L

This is the first study to comprehensively examine how different midthigh muscle imaging techniques and histology compare with one another in participants that performed 10 weeks of resistance training. Our study suggests that histology results show poor agreement with results yielded from other common muscle imaging techniques, and researchers should be aware of this limitation.

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 (p2max, 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 SUMMARYResistance training is largely underappreciated as a method to improve endurance performance, despite reports showing it may improve mitochondrial function.Although 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.Prior 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.

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

We investigated the effects of aging and long-term physical activity on markers of mitochondrial function and dynamics in the cortex and cerebellum of female rats. Additionally, we interrogated markers of oxidative damage and antioxidants. Thirty-four female Lewis rats were separated into three groups. A young group (YNG, n = 10) was euthanized at 6 months of age. Two other groups were aged to 15 months and included a physical activity group (MA-PA, n = 12) and a sedentary group (MA-SED, n = 12). There were no age effects for any of the variables investigated, except for SOD2 protein levels in the cortex (+6.5%, p = 0.012). Long-term physical activity increased mitochondrial complex IV activity in the cortex compared to YNG (+85%, p = 0.016) and MA-SED (+82%, p = 0.023) and decreased carbonyl levels in the cortex compared to YNG (-12.49%, p = 0.034). Our results suggest that the mitochondrial network and redox state of the brain of females may be more resilient to the aging process than initially thought. Further, voluntary wheel running had minimal beneficial effects on brain markers of oxidative damage and mitochondrial physiology.

We sought to determine the effects of long-term voluntary wheel running on markers of long interspersed nuclear element-1 (L1) in skeletal muscle, liver, and the hippocampus of female rats. In addition, markers of the cGAS-STING DNA-sensing pathway that results in inflammation were interrogated. Female Lewis rats ( n = 34) were separated into one of three groups including a 6-mo-old group to serve as a young comparator group (CTL, n = 10), a group that had access to a running wheel for voluntary wheel running (EX, n = 12), and an age-matched group that did not (SED, n = 12). Both SED and EX groups were carried out from 6 mo to 15 mo of age. There were no significant differences in L1 mRNA expression for any of the tissues between groups. Methylation of the L1 promoter in the soleus and hippocampus was significantly higher in SED and EX than in CTL group ( P < 0.05). ORF1p expression was higher in older SED and EX rats than in CTL rats for every tissue ( P < 0.05). There were no differences between groups for L1 mRNA or cGAS-STING pathway markers. Our results suggest there is an increased ORF1 protein expression across tissues with aging that is not mitigated by voluntary wheel running. In addition, although previous data imply that L1 methylation changes may play a role in acute exercise for L1 RNA expression, this does not seem to occur during extended periods of voluntary wheel running.

Background: In the endothelium, tumor necrosis factor (TNF) binding to TNF receptor-I (TNFR-I) facilitates monocyte recruitment and consequently the development of atherosclerosis. The prevalence of inflammation, endothelial dysfunction, and subclinical atherosclerosis is higher in the African American (AA) population. This is supported by in vitro evidence demonstrating heightened inflammatory response and atherogenic potential in endothelial cells (ECs) from AA donors. Evidence suggests that high unidirectional laminar shear stress (HSS), as an exercise mimetic, can mitigate some aspects of racial differences in endothelial function at the cellular level. Therefore, we hypothesized that TNF-induced monocyte adhesion as well as TNFR-I signaling complex expression/activity would be exacerbated in AA derived ECs. Further, we hypothesized that HSS would attenuate potential racial differences. Methods: THP-1 monocytes and human umbilical vein ECs (HUVECs) from Caucasian American (CA) and AA donors were used in a co-culture system to examine racial differences in monocyte adhesion. An in vitro exercise mimetic model was applied to investigate the potential modulatory effect of HSS. Results: THP-1 adherence appeared elevated in untreated and TNF-treated AA ECs compared to CA ECs, but not statistically significant. Additionally, we report no significant racial differences in the expression of TNFR-I signaling complex or TNF-induced activation of NF-κB. Application of HSS significantly increased the expression and shedding of TNFR-I in both racial groups. Conclusion: Our data do not support TNF-induced NF-κB activation as a potential mediator of racial disparity or HSS atheroprotective effect. Future research should investigate the role of other pathways activated by TNFR-I signaling complex.

We examined if resistance training affected muscle NAD+ and NADH concentrations as well as nicotinamide phosphoribosyltransferase (NAMPT) protein levels and sirtuin (SIRT) activity markers in middle-aged, untrained (MA) individuals. MA participants (59±4 years old; n=16) completed 10 weeks of full-body resistance training (2 d/wk). Body composition, knee extensor strength, and vastus lateralis muscle biopsies were obtained prior to training (Pre) and 72 hours following the last training bout (Post). Data from trained college-aged men (22±3 years old, training age: 6±2 years old; n=15) were also obtained for comparative purposes. Muscle NAD+ (+127%, p0.10). Interestingly, muscle citrate synthase activity levels (i.e., mitochondrial density) increased in MA participants from Pre to Post (+183%, p

Background Cancer Anorexia Cachexia Syndrome (CACS) is a distinct atrophy disease negatively influencing multiple aspects of clinical care and patient quality of life. Although it directly causes 20% of all cancer‐related deaths, there are currently no model systems that encompass the entire multifaceted syndrome, nor are there any effective therapeutic treatments. Methods A novel model of systemic metastasis was evaluated for the comprehensive CACS (metastasis, skeletal muscle and adipose tissue wasting, inflammation, anorexia, anemia, elevated protein breakdown, hypoalbuminemia, and metabolic derangement) in both males and females. Ex vivo skeletal muscle analysis was utilized to determine ubiquitin proteasome degradation pathway activation. A novel ketone diester (R/S 1,3‐Butanediol Acetoacetate Diester) was assessed in multifaceted catabolic environments to determine anti‐atrophy efficacy. Results Here, we show that the VM‐M3 mouse model of systemic metastasis demonstrates a novel, immunocompetent, logistically feasible, repeatable phenotype with progressive tumor growth, spontaneous metastatic spread, and the full multifaceted CACS with sex dimorphisms across tissue wasting. We also demonstrate that the ubiquitin proteasome degradation pathway was significantly upregulated in association with reduced insulin‐like growth factor‐1/insulin and increased FOXO3a activation, but not tumor necrosis factor‐α‐induced nuclear factor‐kappa B activation, driving skeletal muscle atrophy. Additionally, we show that R/S 1,3‐Butanediol Acetoacetate Diester administration shifted systemic metabolism, attenuated tumor burden indices, reduced atrophy/catabolism and mitigated comorbid symptoms in both CACS and cancer‐independent atrophy environments. Conclusions Our findings suggest the ketone diester attenuates multifactorial CACS skeletal muscle atrophy and inflammation‐induced catabolism, demonstrating anti‐catabolic effects of ketone bodies in multifactorial atrophy.

Female athletes are at an elevated risk for tearing their anterior cruciate ligament, compared to their male counterparts. Though injury screening clinical tests and neuromuscular training programs have been widely implemented, injury rates remain high among female athletes. The purpose of this study was to examine the relationship between serum relaxin concentrations and knee valgus during three clinical tests (single leg squat, drop vertical jump, and single leg crossover dropdown). Twenty-two female athletes volunteered. Participants were scheduled for collection during the mid-luteal phase, when serum relaxin concentrations are known to be measurable. Blood samples were collected, and serum relaxin concentrations were quantified. Kinematic data were collected while participants performed the three clinical tests. Regression analyses revealed statistically significant relationships between serum relaxin concentrations and knee valgus throughout all tests. These findings suggest that serum relaxin concentrations and knee valgus are not independent of each other and more holistic approaches may be necessary to truly map out the risk for injury and ultimately reduce the rate of anterior cruciate ligament injuries. Thus, concluding that knee valgus, a highly utilized modifiable biomechanical risk factor, and relaxin, a hormone that has been associated with anterior cruciate ligament injury in female athletes, are related to each other.

Limited pre-clinical and clinical data suggest theacrine or theacrine-based supplements modulate biological processes associated with lipid metabolism and aging. Herein, we sought to examine if 12 weeks of daily supplementation with a theacrine-based supplement (termed NAD3®; 312 mg of combined Wasabia japonica freeze-dried rhizome standardized for isothicyantes, theacrine, and copper (I)niacin chelate) altered serum lipids as well as select nicotinamide adenine dinucleotide (NAD+)-associated metabolites in peripheral blood mononuclear cells (PBMCs). Twenty-eight participants (12 males, 16 females) were randomly assigned to receive either NAD3 (n = 13; age: 52 ± 7 years old, body mass index: 29.0 ± 5.0 kg/m2) or a cellulose placebo (n = 15; age: 51 ± 5 years old, body mass index: 28.3 ± 3.9 kg/m2). Blood samples were obtained in mornings following overnight fasts prior to supplementation (Pre) and following the 12-week intervention (Post). PBMCs were freshly isolated and prepared for targeted NAD+ metabolomics, and serum as well as whole blood was assayed for blood lipids and other safety markers through a commercial laboratory. Significant interactions (p < 0.05) were observed for total cholesterol, LDL cholesterol, and LDL: HDL ratio and post hoc analyses indicated these biomarkers significantly decreased with NAD3 supplementation (Pre-to-Post percent decreases were 11.1, 15.2, and −18.9%, respectively). A significant interaction was also observed for PBMC NAD+: NADH values, where levels trended downward from Pre to Post in the CTL group (p = 0.081) and values at Post were greater in NAD3 versus CTL (p = 0.023). No interactions were observed for systolic/diastolic blood pressure, body mass, or blood markers indicative of clinical safety. Although participant numbers were limited, these first-in-human data demonstrate a theacrine-based NAD3 supplement can favorably alter biomarkers of lipid metabolism and cellular NAD+ status. However, the latter data are limited to targeted NAD+ metabolites, and the effects of supplementation on other cellular metabolites or mechanisms related to the observed outcomes need to be further explored.

This study assesses if a lower dose of whey protein can provide similar benefits to those shown in previous work supplementing Army Initial Entry Training (IET) Soldiers with two servings of whey protein (WP) per day. Eighty-one soldiers consumed one WP or a calorie matched carbohydrate (CHO) serving/day during IET (WP: n = 39, height = 173 ± 8 cm, body mass = 76.8 ± 12.8 kg, age = 21 ± 3 years; CHO: n = 42, 175 ± 8 cm, 77.8 ± 15.3 kg, 23 ± 4 years). Physical performance (push-ups, sit-ups, and a two-mile run) was assessed during weeks two and eight. All other measures (dietary intake, body composition, blood biomarkers) at weeks one and nine. There was a significant group difference for fat mass (p = 0.044) as WP lost 2.1 ± 2.9 kg and had a moderate effect size (Cohen's d: −0.24), whereas the CHO group lost 0.9 ± 2.5 kg and had only a small effect size (d: −0.1). There was no significant group-by-time interaction on fat-free mass (p = 0.069). WP gained 1.2 ± 2.4 (d: 0.1) and CHO gained 0.1 ± 3 (d: 0) kg of FFM on average. There was a significant group by week 1-fat free mass interaction (p = 0.003) indicating individuals with higher initial fat-free mass benefitted more from WP. There were no group differences for push-up (p = 0.514), sit-up (p = 0.429) or run (p = 0.313) performance. For all biomarkers there was a significant effect of time as testosterone (p < 0.01), testosterone to cortisol ratio (p = 0.39), and IGF-1 (p < 0.01) increased across training and cortisol (p = 0.04) and IL-6 (p < 0.01) decreased. There were no differences in groups across IET for any of the biomarkers. We conclude one WP serving is beneficial for FM and for FFM in soldiers with high baseline FFM but may not significantly alter biomarker response or physical performance of IET soldiers who have high relative dietary protein intakes.

We evaluated the effects of higher-load (HL) versus (lower-load) higher-volume (HV) resistance training on skeletal muscle hypertrophy, strength, and muscle-level molecular adaptations. Trained men (n = 15, age: 23 ± 3 years; training experience: 7 ± 3 years) performed unilateral lower-body training for 6 weeks (3× weekly), where single legs were randomly assigned to HV and HL paradigms. Vastus lateralis (VL) biopsies were obtained prior to study initiation (PRE) as well as 3 days (POST) and 10 days following the last training bout (POSTPR). Body composition and strength tests were performed at each testing session, and biochemical assays were performed on muscle tissue after study completion. Two-way within-subject repeated measures ANOVAs were performed on most dependent variables, and tracer data were compared using dependent samples t-tests. A significant interaction existed for VL muscle cross-sectional area (assessed via magnetic resonance imaging; interaction p = 0.046), where HV increased this metric from PRE to POST (+3.2%, p = 0.018) whereas HL training did not (−0.1%, p = 0.475). Additionally, HL increased leg extensor strength more so than HV training (interaction p = 0.032; HV p

Although transcriptome profiling has been used in several resistance training studies, the associated analytical approaches seldom provide in-depth information on individual genes linked to skeletal muscle hypertrophy. Therefore, a secondary analysis was performed herein on a muscle transcriptomic dataset we previously published involving trained college-aged men (n = 11) performing two resistance exercise bouts in a randomized and crossover fashion. The lower-load bout (30 Fail) consisted of 8 sets of lower body exercises to volitional fatigue using 30% one-repetition maximum (1 RM) loads, whereas the higher-load bout (80 Fail) consisted of the same exercises using 80% 1 RM loads. Vastus lateralis muscle biopsies were collected prior to (PRE), 3 h, and 6 h after each exercise bout, and 58 genes associated with skeletal muscle hypertrophy were manually interrogated from our prior microarray data. Select targets were further interrogated for associated protein expression and phosphorylation induced-signaling events. Although none of the 58 gene targets demonstrated significant bout x time interactions, ~57% (32 genes) showed a significant main effect of time from PRE to 3 h (15↑ and 17↓, p < 0.01), and ~26% (17 genes) showed a significant main effect of time from PRE to 6 h (8↑ and 9↓, p < 0.01). Notably, genes associated with the myostatin (9 genes) and mammalian target of rapamycin complex 1 (mTORC1) (9 genes) signaling pathways were most represented. Compared to mTORC1 signaling mRNAs, more MSTN signaling-related mRNAs (7 of 9) were altered post-exercise, regardless of the bout, and RHEB was the only mTORC1-associated mRNA that was upregulated following exercise. Phosphorylated (phospho-) p70S6K (Thr389) (p = 0.001; PRE to 3 h) and follistatin protein levels (p = 0.021; PRE to 6 h) increased post-exercise, regardless of the bout, whereas phospho-AKT (Thr389), phospho-mTOR (Ser2448), and myostatin protein levels remained unaltered. These data continue to suggest that performing resistance exercise to volitional fatigue, regardless of load selection, elicits similar transient mRNA and signaling responses in skeletal muscle. Moreover, these data provide further evidence that the transcriptional regulation of myostatin signaling is an involved mechanism in response to resistance exercise.

We sought to determine if manipulating resistance training (RT) variables differentially altered the expression of select sarcoplasmic and myofibril proteins as well as myofibrillar spacing in myofibers. Resistance-trained men (n = 20; 26 ± 3 years old) trained for 8 weeks where a randomized leg performed either a standard (CON) or variable RT protocol (VAR: manipulation of load, volume, muscle action, and rest intervals at each RT session). A pre-training (PRE) vastus lateralis biopsy was obtained from a randomized single leg, and biopsies were obtained from both legs 96 h following the last training bout. The sarcoplasmic protein pool was assayed for proteins involved in energy metabolism, and the myofibril protein pool was assayed for relative myosin heavy chain (MHC) and actin protein abundances. Sections were also histologically analyzed to obtain myofibril spacing characteristics. VAR resulted in ~12% greater volume load (VL) compared to CON (p 2), p = 0.006; VAR: 13.9% (743.2 μm2), p = 0.01 vs. PRE for both], but without significant differences between protocols (p = 0.79). Neither RT protocol affected a majority of assayed proteins related to energy metabolism, but both training protocols increased hexokinase 2 protein levels and decreased a mitochondrial beta-oxidation marker (VLCAD protein; p p p p p = 0.048), but not for the CON (4.53%; p = 0.979). In contrast, there was an increase in percent area occupied by non-contractile space from PRE to VAR (10.14%; p = 0.048), but not PRE to CON (0.72%; p = 0.979). In conclusion, while both RT protocols increased muscle fiber hypertrophy, a higher volume-load where RT variables were frequently manipulated increased non-contractile spacing in resistance-trained individuals.

Background: The gut microbiome contributes to numerous physiological processes in humans, and diet and exercise are known to alter both microbial composition and mood. We sought to explore the effect of a 10-week resistance training (RT) regimen with or without peanut protein supplementation (PPS) in untrained young adults on fecal microbiota and mood disturbance (MD). Methods: Participants were randomized into PPS (n = 25) and control (CTL [no supplement]; n = 24) groups and engaged in supervised, full-body RT twice a week. Measures included body composition, fecal microbe relative abundance, alpha- and beta-diversity from 16 s rRNA gene sequencing with QIIME2 processing, dietary intake at baseline and following the 10-week intervention, and post-intervention MD via the profile of mood states (POMS) questionnaire. Independent samples t-tests were used to determine differences between PPS and CTL groups. Paired samples t-tests investigated differences within groups. Results: Our sample was mostly female (69.4%), white (87.8%), normal weight (body mass index 24.6 ± 4.2 kg/m2), and 21 ± 2.0 years old. Shannon index significantly increased from baseline in all participants (p = 0.040), with no between-group differences or pre-post beta-diversity dissimilarities. Changes in Blautia abundance were associated with the positive POMS subscales, Vigor and self-esteem-related-affect (SERA) (rho = −0.451, p = 0.04; rho = −0.487, p = 0.025, respectively). Whole tree phylogeny changes were negatively correlated with SERA and Vigor (rho = −0.475, p = 0.046; rho = −0.582, p = 0.011, respectively) as well as change in bodyfat percentage (rho = −0.608, p = 0.007). Mediation analysis results indicate changes in PD Whole Tree Phylogeny was not a significant mediator of the relationship between change in fat-free mass and total MD. Conclusions: Mood state subscales are associated with changes in microbial taxa and body composition. PD Whole Tree Phylogeny increased following the 10-week RT regimen; further research is warranted to explore how RT-induced changes in microbial diversity are related to changes in body composition and mood disturbance.

Protein supplementation is a commonly employed strategy to enhance resistance training adaptations. However, little research to date has examined if peanut protein supplementation is effective in this regard. Thus, we sought to determine if peanut protein supplementation (PP, 75 total g/d of powder providing 30 g/d protein, &gt, 9.2 g/d essential amino acids, ~315 kcal/d) affected resistance training adaptations in college-aged adults. Forty-seven college-aged adults (n = 34 females, n = 13 males) with minimal prior training experience were randomly assigned to a PP group (n = 18 females, n = 5 males) or a non-supplement group (CTL, n = 16 females, n = 8 males) (ClinicalTrials.gov trial registration NCT04707963, registered 13 January 2021). Body composition and strength variables were obtained prior to the intervention (PRE). Participants then completed 10 weeks of full-body resistance training (twice weekly) and PP participants consumed their supplement daily. POST measures were obtained 72 h following the last training bout and were identical to PRE testing measures. Muscle biopsies were also obtained at PRE, 24 h following the first exercise bout, and at POST. The first two biopsy time points were used to determine myofibrillar protein synthesis (MyoPS) rates in response to a naïve training bout with or without PP, and the PRE and POST biopsies were used to determine muscle fiber adaptations in females only. Dependent variables were analyzed in males and females separately using two-way (supplement × time) repeated measures ANOVAs, unless otherwise stated. The 24-h integrated MyoPS response to the first naïve training bout was similar between PP and CTL participants (dependent samples t-test p = 0.759 for females, p = 0.912 for males). For males, the only significant supplement × time interactions were for DXA-derived fat mass (interaction p = 0.034) and knee extensor peak torque (interaction p = 0.010), these variables significantly increased in the CTL group (p &lt, 0.05), but not the PP group. For females, no significant supplement × time interactions existed, although interactions for whole body lean tissue mass (p = 0.088) and vastus lateralis thickness (p = 0.099) approached significance and magnitude increases in these characteristics favored the PP versus CTL group. In summary, this is the second study to determine the effects of PP supplementation on resistance training adaptations. While PP supplementation did not significantly enhance training adaptations, the aforementioned trends in females, the limited n-size in males, and this being the second PP supplementation study warrant more research to determine if different PP dosing strategies are more effective than the current approach.

Resistance training increases muscle fiber hypertrophy, but the morphological adaptations that occur within muscle fibers remain largely unresolved. Fifteen males with minimal training experience (24±4years, 23.9±3.1kg/m2 body mass index) performed 10weeks of conventional, full-body resistance training (2× weekly). Body composition, the radiological density of the vastus lateralis muscle using peripheral quantitative computed tomography (pQCT), and vastus lateralis muscle biopsies were obtained 1week prior to and 72h following the last training bout. Quantification of myofibril and mitochondrial areas in type I (positive for MyHC I) and II (positive for MyHC IIa/IIx) fibers was performed using immunohistochemistry (IHC) techniques. Relative myosin heavy chain and actin protein abundances per wet muscle weight as well as citrate synthase (CS) activity assays were also obtained on tissue lysates. Training increased whole-body lean mass, mid-thigh muscle cross-sectional area, mean and type II fiber cross-sectional areas (fCSA), and maximal strength values for leg press, bench press, and deadlift (pp=0.018), albeit CS activity levels remained unaltered with training suggesting a discordance between these assays. Interestingly, although pQCT-derived muscle density increased with training (p=0.036), suggestive of myofibril packing, a positive association existed between training-induced changes in this metric and changes in mean fiber myofibril area (r=0.600, p=0.018). To summarize, our data imply that shorter-term resistance training promotes a proportional expansion of the area occupied by myofibrils and a disproportional expansion of the area occupied by mitochondria in type I and II fibers. Additionally, IHC and biochemical techniques should be viewed independently from one another given the lack of agreement between the variables assessed herein. Finally, the pQCT may be a viable tool to non-invasively track morphological changes (specifically myofibril density) in muscle tissue.

Objective Long INterspersed Element-1 (L1) is an autonomous transposable element in the genome. L1 transcripts that are not reverse transcribed back into the genome can accumulate in the cytoplasm and activate an inflammatory response via the cyclic GMP-AMP (cGAS)-STING pathway. We examined skeletal muscle L1 markers as well as STING protein levels in 10 older individuals (63 ± 11 y, BMI = 30.2 ± 6.8 kg/m2) with end-stage osteoarthritis (OA) undergoing total hip (THA, n = 4) or knee (TKA, n = 6) arthroplasty versus 10 young, healthy comparators (Y, 22 ± 2 y, BMI = 23.2 ± 2.5 kg/m2). For OA, muscle was collected from surgical (SX) and contralateral (CTL) sides whereas single vastus lateralis samples were collected from Y. Results L1 mRNA was higher in CTL and SX compared to Y (p

Naked mole-rats (NMR) and Damaraland mole-rats (DMR) are the only two eusocial mammals known. Both species exhibit extraordinary longevity for their body size, high tolerance to hypoxia and oxidative stress and high reproductive output; these collectively defy the concept that all life-history traits should be negatively correlated. However, when life-history traits share similar underpinning physiological mechanisms, these may be positively associated with each other. Here, we propose that the bioenergetic properties of mole-rats share a potential common mechanism. We adopted a top-down perspective measuring the bioenergetic properties at the organismal, cellular, and molecular level in both species and the biological significance of these properties were compared with the same measures in Siberian hamsters and C57BL/6 mice, chosen for their similar body size to the mole-rat species. We found mole-rats shared several bioenergetic properties that differed from their comparator species, including low basal metabolic rates, a high dependence on glycolysis rather than on oxidative phosphorylation for ATP production, and low proton conductance across the mitochondrial inner membrane. These shared mole-rat features could be a result of evolutionary adaptation to tolerating variable oxygen atmospheres, in particular hypoxia, and may in turn be one of the molecular mechanisms underlying their extremely long lifespans.

Mild cognitive impairment (MCI) designates the boundary area between cognitive function in natural aging and dementia, and this is viewed as a therapeutic window to prevent the occurrence of dementia. The current study investigated the neurocognitive effects of oral creatine (Cr) supplementation in young female Wistar rats that received intracerebroventricular injections of lipopolysaccharide (LPS) to mimic MCI. Neuromolecular changes within the dentate gyrus were analyzed following behavioral testing. We also investigated both neurocognitive and neuromolecular changes following Cr supplementation in the absence of LPS in young female Wistar rats to further investigate mechanisms. Interestingly, based on trial 2 of Barnes maze test, Cr supplementation ameliorated spatial learning and memory deficit induced by LPS, shown by decreased latency time and errors to reach the escape box (p &lt, 0.0001, n = 12). Cr supplementation also attenuated recognition memory deficit induced by LPS, shown by increased amount of time taken to explore the new object (p = 0.002, n = 12) during novel object recognition testing. Within the dentate gyrus, Cr supplementation in LPS injected rats upregulated mTORC1 signaling (p = 0.026 for mTOR phosphorylation, p = 0.002 for p70S6K phosphorylation, n = 8) as well as the synapsin (p = 0.008) and PSD-95 synaptic proteins (p = 0.015), in comparisons to LPS injected rats. However, Cr supplementation failed to further enhance spatial memory and recognition memory in the absence of LPS. In conclusion, Cr ameliorates LPS-induced cognitive impairment in a rodent MCI model. Mechanistically, these phenotypic effects may, in part, be mitigated via an upregulation of mTORC1 signaling, and an enhancement in synaptogenesis in the dentate gyrus. While preliminary, these findings may inform future research investigating neurocognitive effects of Cr for MCI patients.