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.