Acute effects of MitoQ on vascular endothelial function are influenced by cardiorespiratory fitness and baseline FMD in middle-aged and older adults.

A key mechanism promoting vascular endothelial dysfunction is mitochondrial-derived reactive oxygen species (mtROS). Aerobic exercise preserves endothelial function in preclinical models by lowering mtROS. However, the effects of mtROS on endothelial function in exercising and non-exercising adults is limited. In a double-blind, randomized, placebo-controlled crossover study design 23 (10 M/13 F, age 62.1 ± 11.5 years) middle-aged and older (MA/O, ≥45 years) adults were divided into two groups: exercisers (EX, n = 11) and non-exercisers (NEX, n = 12). All participants had endothelial function (brachial artery flow-mediated dilatation, FMDBA) measured before and ∼1 h after mitoquinone mesylate (MitoQ) (single dose, 80 mg) and placebo supplementation. A two-way repeated measures ANOVA was used to determine the effects of MitoQ and placebo on FMDBA. Pearson correlations assessed the association between the change in FMDBA with MitoQ and baseline FMDBA and cardiorespiratory fitness (CRF). Compared with placebo, MitoQ increased FMDBA in NEX by + 2.1% (MitoQ pre: 4.9 ± 0.4 vs. post: 7.0 ± 0.4 %, P = 0.004, interaction) but not in EX (P = 0.695, interaction). MitoQ also increased endothelial function in adults with a FMDBA <6% (P < 0.0001, interaction) but not >6% (P = 0.855, interaction). Baseline FMDBA and CRF were correlated (r = 0.44, P = 0.037), whereas the change in FMDBA with MitoQ was inversely correlated with CRF (r = -0.66, P < 0.001) and baseline FMDBA (r = -0.73, P < 0.0001). The relationship between the change in FMDBA and baseline FMDBA remained correlated after adjusting for CRF (r = -0.55, P = 0.007). These data demonstrate that MitoQ acutely improves FMDBA in NEX and EX adults who have a baseline FMDBA <6%. KEY POINTS: A key age-related change contributing to increased cardiovascular disease (CVD) risk is vascular endothelial dysfunction due to increased mitochondrial-derived reactive oxygen species (mtROS). Aerobic exercise preserves endothelial function via suppression of mtROS in preclinical models but the evidence in humans is limited. In the present study, a single dose of the mitochondria-targeted antioxidant, mitoquinone mesylate (MitoQ), increases endothelial function in non-exercisers with lower cardiorespiratory fitness (CRF) but not in exercisers with higher CRF. The acute effects of MitoQ on endothelial function in middle-aged and older adults (MA/O) are influenced by baseline endothelial function independent of CRF. These data provide initial evidence that the acute MitoQ-enhancing effects on endothelial function in MA/O adults are influenced, in part, via CRF and baseline endothelial function.

Cardiorespiratory fitness is associated with estimates of myocardial perfusion: influence of age and sex.

Cardiorespiratory fitness (CRF) and the subendocardial viability ratio (SEVR) decline with age and predict future cardiovascular disease (CVD) events in a sex-dependent manner. However, the relation between CRF and SEVR in apparently healthy males and females across the age span is largely unknown. We hypothesized higher CRF is associated with greater SEVR in older females but not in males. Two-hundred sixty-two (126 M/136 F, age range 20-84 yr) participants underwent measures of CRF (maximal O2 consumption, V̇o2max) and SEVR (pulse wave analysis, PWA). A two-way analysis of variance (ANOVA) was used to examine differences in baseline characteristics between younger (<45 yr) and middle-aged and older (MA/O, ≥45 yr) males and females. Bivariate correlations assessed the relation between CRF, SEVR, and age in males and females. Partial correlations adjusted for CVD risk factors and medications. MA/O females had the lowest CRF and SEVR compared with all other groups (P < 0.05, both). SEVR was negatively correlated with age (r = -0.29) and positively correlated with CRF (r = 0.53) in females (P < 0.05, both) that persisted after controlling for CVD risk factors and medications (P < 0.05, all). SEVR was correlated with CRF in males only after adjusting for CVD risk factors and medications (r = 0.26, P < 0.05). These findings collectively demonstrate higher CRF is associated with greater SEVR in males and females after adjusting for CVD risk factors and medications, therefore highlighting subtle sex-specific nuances that warrant further investigation.NEW & NOTEWORTHY Cardiorespiratory fitness (CRF) and the subendocardial viability ratio (SEVR) are independent predictors of mortality and decline with age. However, the sex-specific relationship between CRF and SEVR with aging in adult males and females is unknown. Our findings demonstrate higher CRF is associated with greater age-related SEVR in males and females, after adjusting for traditional cardiovascular disease (CVD) risk factors and medications. However, subtle sex-related nuances exist in the relationship between SEVR and CRF that require further investigation.

Cardiorespiratory and Muscular Fitness in Children and Adolescents with Obesity.

PURPOSE OF REVIEW: Examine the current state of literature related to the impact of obesity in children and adolescents on health-related physical fitness and the resultant cardiometabolic disease risk. RECENT FINDINGS: Cardiorespiratory fitness of children and adolescents has declined over the past few decades which corresponds with an increase in obesity rates. Children with obesity are more likely to have low cardiorespiratory fitness which is associated with higher cardiometabolic disease risk and poorer mental health. The impact of obesity on muscular fitness in children and adolescents is more difficult to ascertain, but in general measures of physical function are lower in children with obesity which has also been associated with higher cardiometabolic disease risk. Components of health-related physical fitness are trending negatively in children and adolescents and appear to be related to the increase in prevalence of obesity. The resultant cardiometabolic disease risk has also risen which suggests a greater disease burden in the future. These disparaging findings highlight the need for aggressive interventions to improve physical fitness in children and adolescents.

Postabsorptive muscle protein synthesis is higher in outpatients as compared to inpatients.

Several factors affect muscle protein synthesis (MPS) in the postabsorptive state. Extreme physical inactivity (e.g., bedrest) may reduce basal MPS, whereas walking may augment basal MPS. We hypothesized that outpatients would have a higher postabsorptive MPS than inpatients. To test this hypothesis, we conducted a retrospective analysis. We compared 152 outpatient participants who arrived at the research site the morning of the MPS assessment with 350 Inpatient participants who had an overnight stay in the hospital unit before the MPS assessment the following morning. We used stable isotopic methods and collected vastus lateralis biopsies ∼2 to 3 h apart to assess mixed MPS. MPS was ∼12% higher (P < 0.05) for outpatients than inpatients. Within a subset of participants, we discovered that after instruction to limit activity, outpatients (n = 13) took 800 to 900 steps in the morning to arrive at the unit, seven times more steps than inpatients (n = 12). We concluded that an overnight stay in the hospital as an inpatient is characterized by reduced morning activity and causes a slight but significant reduction in MPS compared with participants studied as outpatients. Researchers should be aware of physical activity status when designing and interpreting MPS results.NEW & NOTEWORTHY The postabsorptive muscle protein synthesis rate is lower in the morning after an overnight inpatient hospital stay compared with an outpatient visit. Although only a minimal amount of steps was conducted by outpatients (∼900), this was enough to increase postabsorptive muscle protein synthesis rate.

Perivascular adipose tissue-mediated arterial stiffening in aging and disease: An emerging translational therapeutic target?

Cardiovascular diseases (CVD) are the leading cause of mortality in modernized societies. Arterial stiffening with aging and disease is a key pathological event leading to increased CVD morbidity and mortality. Perivascular adipose tissue (PVAT) is a fat depot not widely studied yet has direct and profound effects on arterial stiffening. Identifying PVAT as a novel therapeutic target to lower arterial stiffness and thereby CVD risk has potentially important clinical ramifications. Thus, herein, we will overview the current preclinical evidence and the associated mechanisms for PVAT to promote arterial stiffness with aging and other disease conditions. We will also discuss viable translational lifestyle and pharmacological interventions for altering PVAT function that may de-stiffen arteries. Last, the translational potential for PVAT as a therapeutic target to lower arterial stiffness and CVD risk for clinical populations will be discussed.

Caffeine ingestion alters central hemodynamics following aerobic exercise in middle-aged men.

PURPOSE: To examine the acute influence of caffeine on post-exercise central blood pressures, arterial stiffness, and wave reflection properties. METHODS: In a double-blind randomized placebo-controlled crossover study design, ten middle-aged males (55 ± 5 year) completed two exercise trials after ingestion of caffeine (400 mg) or placebo. Measurements were taken before and 30 min post-ingestion via cuff-based pulse wave analysis (PWA) and carotid-femoral pulse wave velocity (PWV). Participants performed a 40-min cycling bout at 70% HRmax with matched workloads between trials. PWA and PWV were reassessed 30 min post-exercise. RESULTS: Prior to exercise, compared to placebo, caffeine increased brachial systolic blood pressure (bSBP) (+ 12.3 ± 2.4 mmHg; p = 0.004), brachial diastolic blood pressure (bDBP) (+ 7.7 ± 0.9 mmHg; p = 0.011), central systolic blood pressure (cSBP) (+ 11.1 ± 2.1 mmHg; p = 0.005) and central diastolic blood pressure (cDBP) (+ 7.6 ± 1.0 mmHg; p = 0.012). PWV was higher 30 min after pill ingestion (p = 0.021 for time) with a trend for a greater increase in caffeine (p = 0.074 for interaction). bSBP (p = 0.036) and cSBP (p = 0.007) were lower after exercise but remained higher (both p < 0.001) in caffeine compared to placebo. PWV remained higher (p = 0.023) after exercise in caffeine compared to placebo but was not influenced by exercise. At rest, augmentation pressure (AP) and index (AIx) were not influenced by caffeine ingestion. Conversely, AIx was lower (p = 0.009) after exercise in placebo only. CONCLUSION: In healthy and active middle-aged men, pre-exercise caffeine ingestion led to higher central and peripheral systolic blood pressures, PWV and AIx at 30 min post-exercise, indicating an increased left ventricular workload which may have implications for cardiovascular event risk.

Relationship between intermuscular adipose tissue infiltration and myostatin before and after aerobic exercise training.

Intermuscular adipose tissue (IMAT) is associated with impaired skeletal muscle contractile and metabolic function. Myostatin and downstream signaling proteins such as cyclin-dependent kinase 2 (CDK2) contribute to the regulation of adipose and skeletal muscle mass in cell culture and animals models, but this relationship remains incompletely understood in humans. The purpose of this study was to determine if the infiltration of IMAT was associated with skeletal muscle myostatin and downstream proteins before and after 12 wk of aerobic exercise training (AET) in healthy older women (OW; 69 ± 2 yr), older men (OM; 74 ± 3 yr), and young men (YM; 20 ± 1 yr). We found that the infiltration of IMAT was correlated with myostatin and phosphorylated CDK2 at tyrosine 15 [P-CDK2(Tyr15)]. IMAT infiltration was greater in the older subjects and was associated with lower skeletal muscle function and exercise capacity. After 12 wk of AET, there was no change in body weight. Myostatin and P-CDK2(Tyr15) were both decreased after AET, and the reduction in myostatin was associated with decreased IMAT infiltration. The decrease in myostatin and IMAT occurred concomitantly with increased exercise capacity, skeletal muscle size, and function after AET. These findings demonstrate that the reduction in IMAT infiltration after AET in weight stable individuals was accompanied by improvements in skeletal muscle function and exercise capacity. Moreover, the association between myostatin and IMAT was present in the untrained state and in response to exercise training, strengthening the potential regulatory role of myostatin on IMAT.

Short-term intense exercise training reduces stress markers and alters the transcriptional response to exercise in skeletal muscle.

The purpose of this investigation was to examine the influence of short-term intense endurance training on cycling performance, along with the acute and chronic signaling responses of skeletal muscle stress and stability markers. Ten recreationally active subjects (25 ± 2 yr, 79 ± 3 kg, 47 ± 2 ml·kg-1·min-1) were studied before and after a 12-day cycling protocol to examine the effects of short-term intense (70-100% V̇o2max) exercise training on resting and exercise-induced regulation of molecular factors related to skeletal muscle cellular stress and protein stability. Skeletal muscle biopsies were taken at rest and 3 h following a 20-km cycle time trial on days 1 and 12 to measure mRNA expression and protein content. Training improved (P < 0.05) cycling performance by 5 ± 1%. Protein oxidation was unaltered on day 12, while resting SAPK/JNK phosphorylation was reduced (P < 0.05), suggesting a reduction in cellular stress. The maintenance in the myocellular environment may be due to synthesis of cytoprotective markers, along with enhanced degradation of damage proteins, as training tended (P < 0.10) to increase resting protein content of manganese superoxide dismutase and heat shock protein 70 (HSP70), while mRNA expression of MuRF-1 was elevated (P < 0.05). Following training (day 12), the acute exercise-induced transcriptional response of TNF-α, NF-κB, MuRF-1, and PGC1α was attenuated (P < 0.05) compared with day 1 Collectively, these data suggest that short-term intense training enhances protein stability, creating a cellular environment capable of resistance to exercise-induced stress, which may be favorable for adaptation.

Skeletal muscle hypertrophy after aerobic exercise training.

Current dogma suggests that aerobic exercise training has minimal effects on skeletal muscle size. We and others have demonstrated that aerobic exercise acutely and chronically alters protein metabolism and induces skeletal muscle hypertrophy. These findings promote an antithesis to the status quo by providing novel perspective on skeletal muscle mass regulation and insight into exercise countermeasures for populations prone to muscle loss.

The effect of feeding during recovery from aerobic exercise on skeletal muscle intracellular signaling.

We previously reported an increase in skeletal muscle protein synthesis during fasted and fed recovery from nonexhaustive aerobic exercise (Harber et al., 2010). The current study examined skeletal muscle intracellular signaling in the same subjects to further investigate mechanisms of skeletal muscle protein metabolism with and without feeding following aerobic exercise. Eight males (VO2peak: 52 ± 2 ml⁻¹·kg⁻¹·min⁻¹) performed 60-min of cycle ergometry at 72 ± 1% VO2peak on two occasions in a counter-balanced design. Exercise trials differed only in the postexercise nutritional intervention: EX-FED (5 kcal, 0.83 g carbohydrate, 0.37 g protein, 0.03 g fat per kg body weight) and EX-FAST (noncaloric, isovolumic placebo) ingested immediately and one hour after exercise. Muscle biopsies were obtained from the vastus lateralis at rest (on a separate day) and two hours postexercise to assess intracellular signaling via western blotting of p70S6K1, eEF2, 4EBP1, AMPKα and p38 MAPK. p70S6K1 phosphorylation was elevated (p < .05) in EX-FED relative to REST and EX-FAST. eEF2, 4EBP1, AMPKα and p38 MAPK signaling were unaltered at 2 h after exercise independent of feeding status when expressed as the ratio of phosphorylated to total protein normalized to actin. These data demonstrate that feeding after a nonexhaustive bout of aerobic exercise stimulates skeletal muscle p70S6K1 intracellular signaling favorable for promoting protein synthesis which may, as recent literature has suggested, better prepare the muscle for subsequent exercise bouts. These data provide further support into the role of feeding on mechanisms regulating muscle protein metabolism during recovery from aerobic exercise.

Aortic Stiffness Is Associated With Higher Nighttime Ambulatory Blood Pressure in Middle-Aged and Older Adults.

PURPOSE: The objective of this study was to determine the relationship between aortic stiffening and brachial and central ambulatory blood pressure (AMBP) in a nonclinical sample of middle-aged and older adults (MA/O). We hypothesized aortic stiffness would be positively associated with 24-hr, daytime, and nighttime brachial and central AMBP. METHODS: Fifty-one participants aged ≥50 yr (21 males and 30 females, mean age 63.4 ± 9.0 yr) with a body mass index <35 kg/m 2 who also had a resting brachial blood pressure (BP) <160/100 mmHg with or without BP medications were recruited for this cross-sectional analysis. All participants underwent measures of aortic stiffness (carotid-femoral pulse wave velocity [cfPWV]) and 24-hr AMBP monitoring. Bivariate correlations assessed the relationship between cfPWV, brachial, and central AMBP. Partial correlations were used to independently adjust for traditional cardiovascular disease (CVD) risk factors including age, sex, waist circumference, glucose, and augmentation index normalized to heart rate 75 bpm, a surrogate measure of arterial stiffness, and in a multivariable combined model. RESULTS: Nighttime brachial systolic BP ( r = 0.31) and central systolic BP ( r = 0.30) were correlated with cfPWV in the multivariable combined model ( P ≤ .05). Nighttime brachial pulse pressure and central pulse pressure were correlated with cfPWV after independently adjusting for all CVD risk factors ( P ≤ .05, all) but not when combined in the multivariable model ( P > .05). CONCLUSIONS: Higher nighttime brachial and central AMBP with older age are related, in part, to greater aortic stiffening. Therefore, interventions to lower or prevent aortic stiffening may also lower nighttime BP in MA/O adults to lower CVD risk.

Chronic use of Antihypertensive Medications and Peak Exercise Blood Pressure in Adult Men and Women from the BALL ST Cohort.

PURPOSE: To determine if individuals chronically (>1 year) prescribed antihypertensive medications have a normal BP response to peak exercise compared to unmedicated individuals. METHODS: Participants included 2,555 adults from the Ball State Adult Fitness Longitudinal Lifestyle STudy cohort who performed a peak treadmill exercise test. Participants were divided into groups by sex and antihypertensive medication status. Individuals prescribed antihypertensive medications for >1 year were included. Exaggerated and blunted SBP within each group was categorized using the Fitness Registry and the Importance of Exercise: A National Database (FRIEND) and absolute criteria as noted by the Amercian Heart Association. RESULTS: The unmedicated group had a greater prevalence (p < 0.05) of blunted SBP responses, whereas the medicated group had a higher prevalence (p < 0.05) of exaggerated SBP responses using both the FRIEND and absolute criteria. Peak SBP was higher (p < 0.01) in medicated compared to unmedicated participants in the overall cohort when controlling for age and sex, but not after controlling for resting SBP (p = 0.613), risk factors (p = 0.104), or cardiorespiratory fitness (p = 0.191). When men and women were assessed independently, peak SBP remained higher in the medicated women after controlling for age and resting SBP (p = 0.039), but not for men (p = 0.311). Individuals on beta-blockers had a higher peak SBP even after controlling for age, sex, risk factors and cardiorespiratory fitness (p = 0.022). CONCLUSIONS: Individuals on antihypertensive medications have a higher peak SBP response to exercise. Given the prognostic value of exaggerated peak SBP, control of exercise BP should be considered in routine BP assessment and in the treatment of hypertension.

Assessing cardiorespiratory fitness in clinical and community settings: Lessons and advancements in the 100th year anniversary of VO2max.

Cardiorespiratory fitness (CRF) is a well-established biomarker that has applications to all adults across the health and disease spectrum. Despite overwhelming evidence supporting the prognostic utility of CRF, it remains vastly underutilized. CRF is optimally measured via cardiopulmonary exercise testing which may not be feasible to implement on a large scale. Therefore, it is prudent to develop ways to accurately estimate CRF that can be applied in clinical and community settings. As such, several prediction equations incorporating non-exercise information that is readily available from routine clinical encounters have been developed that provide an adequate reflection of CRF that could be implemented to raise awareness of the importance of CRF. Further, technological advances in smartphone apps and consumer-grade wearables have demonstrated promise to provide reasonable estimates of CRF that are widely available, which could enhance the utilization of CRF in both clinical and community settings.

Evaluating current assessment techniques of cardiorespiratory fitness.

INTRODUCTION: Considerable and convincing global data from cohorts across the health spectrum (i.e. apparently healthy to known disease) indicate that cardiorespiratory fitness (CRF) is a major predictor of overall and cardiovascular disease (CVD)-survival, seemingly with greater prognostic resolution compared to other traditional CVD risk factors. Therefore, the assessment of CRF in research and clinical settings is of major importance. AREAS COVERED: In this manuscript, we review the technology of measuring CRF assessed by the 'gold standard,' cardiopulmonary exercise testing (CPET), as well as with various other methods (e.g. estimated metabolic equivalents, 6-minute walk tests, shuttle tests, and non-exercise equations that estimate CRF), all of which provide significant prognostic information for CVD- and all-cause survival. The literature through May 2024 has been cited. EXPERT OPINION: The promotion of physical activity in efforts to improve levels of CRF is needed throughout the world to improve lifespan and, more importantly, healthspan. The routine assessment of CRF should be considered a vital sign that is routinely assessed in clinical practice.

Improving Reporting of Exercise Capacity Across Age Ranges Using Novel Workload Reference Equations.

Exercise capacity (EC) is an important predictor of survival in the general population and in subjects with cardiopulmonary disease. Despite its relevance, considering the percent-predicted workload (%pWL) given by current equations may overestimate EC in older adults. Therefore, to improve the reporting of EC in clinical practice, our main objective was to develop workload reference equations (pWL) that better reflect the relation between workload and age. Using the Fitness Registry and the Importance of Exercise National Database (FRIEND), we analyzed a reference group of 6,966 apparently healthy participants and 1,060 participants with heart failure who underwent graded treadmill cardiopulmonary exercise testing. For the first group, the mean age was 44 years (18 to 79); 56.5% of participants were males and 15.4% had obesity. Peak oxygen consumption was 11.6 ± 3.0 METs in males and 8.5 ± 2.4 METs in females. After partition analysis, we first developed sex-specific pWL equations to allow comparisons to a healthy weight reference. For males, pWL (METs) = 14.1-0.9×10-3×age2 and 11.5-0.87×10-3×age2 for females. We used those equations as denominators of %pWL, and based on their distribution, we determined thresholds for EC classification, with average EC defined by the range corresponding to 85% to 115%pWL. Compared with %pWL using current equations, the new equations yielded better-calibrated %pWL across different age ranges. We also derived body mass index-adjusted pWL equations that better assessed EC in subjects with heart failure. In conclusion, the novel pWL equations have the potential to impact the report of EC in practice.

Local anesthetic effects on gene transcription in human skeletal muscle biopsies.

INTRODUCTION: We examined if epinephrine in the local anesthetic to help control incision-related bleeding interferes with molecular measurements obtained with the Duchenne-Bergström percutaneous needle biopsy technique for sampling human skeletal muscle. METHODS: Three groups received 2.5-3.0 ml of 1% lidocaine in 2 injections: (1) 0.5-1.0 ml superficially, which varied among the groups according to (i) -Epi; intra- and subcutaneous without epinephrine, (ii) +Epi -Fascia; intra- and subcutaneous with epinephrine, avoiding the fascia, and (iii) +Epi +Fascia; intra- and subcutaneous with epinephrine, directing a small amount (∽0.2 ml) into the fascia area; and (2) ∽2.0 ml without epinephrine into the fascia area for all subjects. A muscle biopsy was obtained 5-10 min later for IL-6 and MuRF-1 mRNA levels. RESULTS: IL-6 mRNA levels were low in -Epi and +Epi -Fascia, but ∽300-fold higher in +Epi +Fascia. MuRF-1 mRNA levels were similar among the groups. CONCLUSIONS: Lidocaine with epinephrine can confound intramuscular measurements from needle biopsies, but this can be avoided with a careful injection approach.

Amino acid infusion alters the expression of growth-related genes in multiple skeletal muscles.

BACKGROUND: Exercise and nutritional interventions have been examined independently as countermeasures to offset the loss of skeletal muscle mass with unloading, yet a protocol to completely preserve the soleus has not been identified. Little is known regarding the combined effect of exercise and nutrition on factors regulating skeletal muscle growth. The purpose of this investigation was to evaluate the influence of amino acid (AA) infusion on myogenic (MRF-4, MyoD, and Myogenin), proteolytic (MuRF-1, Atrogin-1, FOXO3A, Calpain-1, Calpain-2, Caspase-3, Cathepsin L1), and cytokine (IL-6, IL-8, and IL-15) mRNA transcripts in two skeletal muscles that respond distinctly to microgravity unloading. METHODS: Muscle biopsies were obtained from the vastus lateralis (VL) and soleus of eight male subjects prior to and after 4 h of AA infusion for analysis of mRNA expression. All subjects performed a standardized exercise bout (45-min treadmill run) 24 h prior to the AA infusion. RESULTS: In the VL, proteolytic factors MuRF-1 and FOXO3A were reduced (44 +/- 9 and 28 +/- 6%, respectively) in response toAA infusion. In the soleus, mRNA transcripts of myogenic factor MRF-4 (91 +/- 36%) and cytokines IL-6, IL-8, and IL-15 were elevated while the proteolytic marker FOXO3A mRNA was reduced by 19 +/- 9%. DISCUSSION: These data suggest that the expression of genes related to skeletal muscle remodeling is altered during acute AA infusion 24 h post-exercise. It appears that increased amino acid availability in concert with exercise may create an intramuscular environment favorable for the prevention of muscle atrophy associated with unloading, which may be particularly beneficial for the soleus.

Mitochondrial-targeted antioxidant ingestion acutely blunts VO2max in physically inactive females.

PURPOSE: To determine the acute effects of a mitochondrial targeting antioxidant (MitoQ) on the metabolic response during exercise. METHODS: Nine (n = 9) physically inactive females (age 47 ± 22 years) performed two trials (Placebo and MitoQ) in a double-blind randomized cross-over design. In both trials, participants performed an exercise protocol consisting of 3-min stages at submaximal workloads followed by a ramp protocol to volitional exhaustion. Participants received either Placebo or MitoQ (80 mg) 1 h prior to exercise. Indirect calorimetry and cardiovascular measurements were collected throughout the duration of the exercise bout. RESULTS: Submaximal metabolic and cardiovascular variables were not different between trials (p > 0.05). VO2max was higher (p = 0.03) during Placebo (23.5 ± 5.7 mL kg min-1 ) compared to MitoQ (21.0 ± 6.6 mL kg min-1 ). Maximal ventilation was also higher (p = 0.02) in Placebo (82.4 ± 17.7 L/min) compared to MitoQ (75.0 ± 16.8 L/min). Maximal cardiovascular variables and blood lactate were not different between trials (p > 0.05). CONCLUSION: An acute dose of MitoQ blunted VO2max , which was primarily mediated by impairment of ventilatory function. These data suggest that the acute accumulation of exercise-induced mitochondrial reactive oxygen species (mtROS) are necessary for maximal aerobic capacity. Further research is warranted on mtROS-antioxidant cell signaling cascades, and how they relate to mitochondrial function during exercise.

Greater aortic perivascular adipose tissue density is associated with aging, aortic stiffness, and central blood pressure in humans.

Aging results in aortic perivascular adipose tissue (aPVAT)-mediated aortic stiffening in preclinical animal models to promote cardiovascular dysfunction. We hypothesized that greater human aPVAT density will be associated with aging, higher aortic stiffness, and blood pressure (BP). Fourteen apparently healthy adults (6 M/8 F, age range 20-79 yr) were recruited for this study. Aortic stiffness, assessed by carotid-femoral pulse wave velocity (cfPWV), resting aortic BP via pulse wave analysis, and aPVAT and abdominal visceral adipose tissue (VAT) density by computed tomography attenuation were acquired. aPVAT and epididymal (visceral) fat from young (4-6 mo) and old (27-29 mo) mice were used for ex vivo-conditioned media intrinsic mechanical stiffness experiments. Compared with younger adults, older adults had higher cfPWV (8.6 ± 0.4 vs. 6.2 ± 0.6 m/s, P < 0.05) and greater aPVAT attenuation (-80.2 ± 2.0 vs. -95.9 ± 1.5 HU, P < 0.05), but not VAT attenuation (P > 0.05). aPVAT-conditioned media from old mice compared with young mice increased intrinsic mechanical stiffness of the aorta (4,519 ± 510 vs. 2,325 ± 563 kPa, P < 0.05), which was not observed with epididymal fat-conditioned media from old mice (P > 0.05). aPVAT, but not VAT density, was positively associated with age (r = 0.89), cfPWV (r = 0.56), resting augmentation index normalized to heart rate 75 (AIxHR75; r = 0.67), aortic systolic BP (r = 0.58), and aortic pulse pressure (PP; r = 0.59; P < 0.05, all) and were independent of VAT density (P < 0.05, all). These data herein provide evidence for aPVAT as a novel fat depot and therapeutic target to lower aortic stiffness and future cardiovascular disease risk with aging in humans.NEW & NOTEWORTHY Aortic perivascular adipose tissue (aPVAT) promotes age-related aortic stiffening in preclinical animal models, but the relation between aPVAT density and cardiovascular function in adults is unknown. We demonstrate that aPVAT, but not abdominal visceral adipose tissue density, is positively associated with aging, aortic stiffness, and higher resting aortic blood pressure in apparently healthy adults. These findings provide novel evidence for aPVAT as a viable therapeutic target for improving cardiovascular function in humans.

Cycle exercise training and muscle mass: A preliminary investigation of 17 lower limb muscles in older men.

Cycling exercise in older individuals is beneficial for the cardiovascular system and quadriceps muscles, including partially reversing the age-related loss of quadriceps muscle mass. However, the effect of cycling exercise on the numerous other lower limb muscles is unknown. Six older men (74 ± 8 years) underwent MRI before and after 12-weeks of progressive aerobic cycle exercise training (3-4 days/week, 60-180 min/week, 60%-80% heart rate reserve, VO2 max: +13%) for upper (rectus femoris, vastii, adductor longus, adductor magnus, gracilis, sartorius, biceps femoris long head, biceps femoris short head, semimembranosus, semitendinosus) and lower (anterior tibial, posterior tibialis, peroneals, flexor digitorum longus, lateral gastrocnemius, medial gastrocnemius, soleus) leg muscle volumes. In the upper leg, cycle exercise training induced hypertrophy (p ≤ 0.05) in the vastii (+7%) and sartorius (+6%), with a trend to increase biceps femoris short head (+5%, p = 0.1). Additionally, there was a trend to decrease muscle volume in the adductor longus (-6%, p = 0.1) and biceps femoris long head (-5%, p = 0.09). In the lower leg, all 7 muscle volumes assessed were unaltered pre- to post-training (-2% to -3%, p > 0.05). This new evidence related to cycle exercise training in older individuals clarifies the specific upper leg muscles that are highly impacted, while revealing all the lower leg muscles do not appear responsive, in the context of muscle mass and sarcopenia. This study provides information for exercise program development in older individuals, suggesting other specific exercises are needed for the rectus femoris and adductors, certain hamstrings, and the anterior and posterior lower leg muscles to augment the beneficial effects of cycling exercise for older adults.