SummaryDisruption of the regulator for G protein signaling 14 (RGS14) knockout (KO) in mice extends their lifespan and has multiple beneficial effects related to healthful aging, that is, protection from obesity, as reflected by reduced white adipose tissue, protection against cold exposure, and improved metabolism. The observed beneficial effects were mediated by improved mitochondrial function. But most importantly, the main mechanism responsible for the salutary properties of the RGS14 KO involved an increase in brown adipose tissue (BAT), which was confirmed by surgical BAT removal and transplantation to wild‐type (WT) mice, a surgical simulation of a molecular knockout. This technique reversed the phenotype of the RGS14 KO and WT, resulting in loss of the improved metabolism and protection against cold exposure in RGS14 KO and conferring this protection to the WT BAT recipients. Another mechanism mediating the salutary features in the RGS14 KO was increased SIRT3. This mechanism was confirmed in the RGS14 X SIRT3 double KO, which no longer demonstrated improved metabolism and protection against cold exposure. Loss of function of the Caenorhabditis elegans RGS‐14 homolog confirmed the evolutionary conservation of this mechanism. Thus, disruption of RGS14 is a model of healthful aging, as it not only enhances lifespan, but also protects against obesity and cold exposure and improves metabolism with a key mechanism of increased BAT, which, when removed, eliminates the features of healthful aging.

To investigate the effects of different loads on system and lower-body kinetics during jump squats, 12 resistance-trained men performed jumps under different loading conditions: 0%, 12%, 27%, 42%, 56%, 71%, and 85% of 1-repetition maximum (1-RM). System power output was calculated as the product of the vertical component of the ground reaction force and the vertical velocity of the bar during its ascent. Joint power output was calculated during bar ascent for the hip, knee, and ankle joints, and was also summed across the joints. System power output and joint power at knee and ankle joints were maximized at 0% 1-RM (p < 0.001) and followed the linear trends (p < 0.001) caused by power output decreasing as the load increased. Power output at the hip was maximized at 42% 1-RM (p = 0.016) and followed a quadratic trend (p = 0.030). Summed joint power could be predicted from system power (p < 0.05), while system power could predict power at the knee and ankle joints under some of the loading conditions. Power at the hip could not be predicted from system power. System power during loaded jumps reflects the power at the knee and ankle, while power at the hip does not correspond to system power.

. Voluntary wheel running augments aortic L-arginine transport and endothelial function in rats with chronic kidney disease. Am J Physiol Renal Physiol 307: F418 -F426, 2014. First published June 25, 2014 doi:10.1152/ajprenal.00014.2014.-Reduced nitric oxide (NO) synthesis contributes to risk for cardiovascular disease in chronic kidney disease (CKD). Vascular uptake of the NO precursor L-arginine (ARG) is attenuated in rodents with CKD, resulting in reduced substrate availability for NO synthesis and impaired vascular function. We tested the effect of 4 wk of voluntary wheel running (RUN) and/or ARG supplementation on endotheliumdependent relaxation (EDR) in rats with CKD. Twelve-week-old male Sprague-Dawley rats underwent 5 ⁄6 ablation infarction surgery to induce CKD, or SHAM surgery as a control. Beginning 4 wk following surgery, CKD animals either remained sedentary (SED) or received one of the following interventions: supplemental ARG, RUN, or combined RUNϩARG. Animals were euthanized 8 wk after surgery, and EDR was assessed. EDR was significantly impaired in SED vs. SHAM animals after 8 wk, in response to ACh (10 Ϫ9 -10 Ϫ5 M) as indicated by a reduced area under the curve (AUC; 44.56 Ϯ 9.01 vs 100 Ϯ 4.58, P Ͻ 0.05) and reduced maximal response (Emax; 59.9 Ϯ 9.67 vs. 94.31 Ϯ 1.27%, P Ͻ 0.05). AUC was not improved by ARG treatment but was significantly improved above SED animals in both RUN and RUNϩARG-treated animals. Maximal relaxation was elevated above SED in RUNϩARG animals only. L-[ 3 H]arginine uptake was impaired in both SED and ARG animals and was improved in RUN and RUNϩARG animals. The results suggest that voluntary wheel running is an effective therapy to improve vascular function in CKD and may be more beneficial when combined with L-arginine. endothelial dysfunction; chronic kidney disease; L-arginine; exercise ENDOTHELIAL DYSFUNCTION CONTRIBUTES to the development of cardiovascular disease (CVD) in patients with chronic kidney disease (CKD) and is primarily associated with a decrease in nitric oxide (NO) production and impaired endothelium-dependent relaxation (EDR) (32). The decline in endothelial function precedes the development of atherosclerosis (17, 48) and has been extensively studied as a potential therapeutic target to treat CVD; however, the specific mechanisms of endothelial dysfunction in CKD have not been fully elucidated. Patients with CKD are more likely to die of CVD than progress to end-stage renal disease (26, 42); therefore, novel treatments to improve endothelial function in CKD are needed to reduce CVD-related mortality in CKD.Insufficient availability of the NO precursor L-arginine likely contributes to reduced NO synthesis in CKD (6). Interestingly, the use of L-arginine in studies of endothelial dysfunction in late-stage CKD has produced mixed results (7, 16) unlike other conditions where it has been largely effective (8,13,15,24). Evidence from cell culture studies suggests that urea and other uremic toxins inhibit L-arginine uptake into endothelial cells (52, 54) by...

The purpose of the present study was to investigate the effects of different configurations of repetitions within a set of deadlifts on the mechanical variables of concentric force, concentric time under tension, impulse, work, power, and fatigue. Eleven resistance trained men (age: 21.9 ± 1.0 years; deadlift 1 repetition maximum: 183.2 ± 38.3 kg) performed four repetitions of the deadlift exercise with a load equivalent to 90% of 1 repetition maximum under three different set configurations: Traditional (continuous repetitions); Doubles cluster (repetitions 1 and 2, and 3 and 4 performed continuously with a 30 s rest inserted between repetitions 2 and 3); Singles cluster (30 s rest provided between repetitions). The order of the sessions was counterbalanced across the subjects and the mechanical variables were calculated during each repetition from the synchronized signals recorded from force platforms and a motion analysis system. Relative to the Traditional set, the insertion of rest periods in the cluster set configurations resulted in greater time under tension (p < 0.001) and therefore, greater impulse (p < 0.001) during the repetitions. Reductions in power were observed during the cluster sets compared to the Traditional set (p = 0.001). The Doubles cluster set resulted in greater fatigue scores for power compared to the Traditional set (p = 0.04). The influence of cluster sets on mechanical variables appears to be mediated by the mechanical characteristics of the exercise (i.e. stretch-shortening cycle) and the competing physiological mechanisms of fatigue and potentiation.

Diets high in salt can lead to endothelial dysfunction, a nontraditional risk factor for cardiovascular disease (CVD). Exercise is known to reduce CVD risk; however, it remains unknown whether chronic physical activity can attenuate salt-induced endothelial dysfunction independent of blood pressure (BP) and whether these changes are due to an upregulation in endogenous antioxidants. Eight-week-old Sprague-Dawley rats were fed either a normal (NS; 0.49%)- or a high (HS; 4.0%)-salt diet and further divided into voluntary wheel running (NS-VWR, HS-VWR) and sedentary (NS, HS) groups for 6 wk. BP was measured weekly and remained unchanged within groups ( P = 0.373). Endothelium-dependent relaxation (EDR) was impaired in the femoral artery of HS compared with NS (38.6 ± 4.0% vs. 65.0 ± 3.6%; P = 0.013) animals, whereas it was not different between NS and HS-VWR (73.4 ± 6.4%; P = 0.273) animals. Incubation with the antioxidants TEMPOL ( P = 0.024) and apocynin ( P = 0.013) improved EDR in HS animals, indicating a role for reactive oxygen species (ROS). Wheel running upregulated the antioxidant superoxide dismutase-2 (SOD-2) ( P = 0.011) under HS conditions and lowered NOX4 and Gp91-phox, two subunits of NADPH oxidase. Wheel running elevated phosphorylated endothelial nitric oxide synthase (eNOS) ( P = 0.014) in HS-fed rats, demonstrating a role for physical activity and eNOS activity under HS conditions. Finally, there was a reduction in EDR ( P = 0.038) when femoral arteries from NS-VWR animals were incubated with TEMPOL or apocynin, suggesting there may be a critical level of ROS needed to maintain endothelial function. In summary, physical activity protected HS-fed rats from reductions in endothelial function, likely through increased SOD-2 levels and reduced oxidative stress. NEW & NOTEWORTHY Our data suggest that voluntary wheel running can prevent impairments in endothelium-dependent relaxation in the femoral artery of rats fed a high-salt diet. This appears to be independent of blood pressure and mediated through a decrease in expression of NADPH oxidases as a result of physical activity. These data suggest that increased chronic physical activity can protect the vasculature from a diet high in salt, likely through a reduction in oxidative stress.

The aims of the present study were to investigate the process of self-selected recovery in a multiple sprint test with a view to using self-selected recovery time as a means of reliably quantifying an individual's ability to resist fatigue in this type of exercise. Twenty physically active exercise science students (means ± SD for age, height, body mass, body fat, and VO2max of the subjects were 21 ± 2 yr, 1.79 ± 0.09 m, 83.7 ± 10.8 kg, 16.6 ± 3.9%, and 52.7 ± 7.2 ml·kg·min, respectively) completed 4 trials of a 12 × 30 m multiple sprint running test under the instruction that they should allow sufficient recovery time between sprints to enable maximal sprint performance to be maintained throughout each trial. Mean recovery times across the 4 trials were 73.9 ± 24.7, 82.3 ± 23.8, 77.6 ± 19.1, and 77.5 ± 13.9 seconds, respectively, with variability across the first 3 trials considered evidence of learning effects. Test-retest reliability across trials 3 to 4 revealed a good level of reliability as evidenced by a coefficient of variation of 11.1% (95% likely range: 8.0-18.1%) and an intraclass correlation coefficient of 0.76 (95% likely range: 0.40-0.91). Despite no change in sprint performance throughout the trials, ratings of perceived exertion increased progressively and significantly (p < 0.001) from a value of 10 ± 2 after sprint 3 to 14 ± 2 after sprint 12. The correlation between relative VO2max and mean recovery time was 0.14 (95% likely range: -0.37-0.58). The results of the present study show that after the completion of 2 familiarization trials, the ability to maintain sprinting performance in a series of repeated sprints can be self-regulated by an athlete to a high degree of accuracy without the need for external timepieces.

The aims of the present study were to investigate the process of self-selected recovery in a multiple sprint test with a view to using self-selected recovery time as a means of reliably quantifying an individual's ability to resist fatigue in this type of exercise.Twenty physically active exercise science students (Means  standard deviation for age, height, body mass, body fat, and VO 2max of the subjects were: 21  2 years, 1.79  0.09 m, 83.7  10.8 kg, 16.6  3.9%, and 52.7 7.2 mlkg -1 min -1 respectively) completed four trials of a 12  30 m multiple sprint running test under the instruction that they should allow sufficient recovery time between sprints to enable maximal sprint performance to be maintained throughout each trial. Mean recovery times across the four trials were 73.9  24.7 s, 82.3  23.8 s, 77.6  19.1 s, and 77.5  13.9 s respectively; with variability across the first three trials considered evidence of learning effects. Test-retest reliability across trials 3-4 revealed a good level of reliability as evidenced by a coefficient of variation of 11.1% (95% likely range: 8.0 to 18.1%) and an intraclass correlation coefficient of 0.76 (95% likely range: 0.40 to 0.91). Despite no change in sprint performance throughout the trials, RPE increased progressively and significantly (p < 0.001) from a value of 10  2 after sprint 3 to 14  2 after sprint 12. The correlation between relative VO 2max and mean recovery time was 0.14 (95% likely range: -0.37 to 0.58). The results of the present study show that following the completion of two familiarization trials, the ability to maintain sprinting performance in a series of repeated sprints can be self-regulated by an athlete to a high degree of accuracy without the need for external timepieces.

Exercise training is key to healthful longevity. Since exercise training compliance is difficult, it would be useful to have a therapeutic substitute that mimicked exercise training. We compared the effects of exercise training in wild type (WT) littermates with adenylyl cyclase type 5 knock out (AC5 KO) mice, a model of enhanced exercise performance. Exercise performance, measured by maximal distance and work to exhaustion, was increased in exercise trained WT to levels already attained in untrained AC5 KO. Exercise training in AC5 KO further enhanced their exercise performance. The key difference in untrained AC5 KO and exercise trained WT was the β-adrenergic receptor signaling, which was decreased in untrained AC5 KO compared to untrained WT but was increased in WT with exercise training. Despite this key difference, untrained AC5 KO and exercise trained WT mice shared similar gene expression, determined by deep sequencing, in their gastrocnemius muscle with 183 genes commonly up or down-regulated, mainly involving muscle contraction, metabolism and mitochondrial function. The SIRT1/PGC-1α pathway partially mediated the enhanced exercise in both AC5 KO and exercise trained WT mice, as reflected in the reduced exercise responses after administering a SIRT1 inhibitor, but did not abolish the enhanced exercise performance in the AC5 KO compared to untrained WT. Increasing oxidative stress with paraquat attenuated exercise performance more in untrained WT than untrained AC5 KO, reflecting the augmented oxidative stress protection in AC5 KO. Blocking nitric oxide actually reduced the enhanced exercise performance in untrained AC5 KO and trained WT to levels below untrained WT, demonstrating the importance of this mechanism. These results suggest that AC5 KO mice, without exercise training, share similar mechanisms responsible for enhanced exercise capacity with chronic exercise training, most importantly increased nitric oxide, and demonstrate more reserve with the addition of exercise training. A novel feature of the enhanced exercise performance in untrained AC5 KO mice is their decreased sympathetic tone, which is also beneficial to patients with cardiovascular disease.