Bioavailable Sulforaphane Quantitation in Plasma by LC-MS/MS Is Enhanced by Blocking Thiols.

Quantifying sulforaphane (SFN) and its thiol metabolites in biological samples using liquid chromatography-tandem mass spectrometry is complicated by SFN's electrophilic nature and the facile dissociation of SFN-thiol conjugates. SFN can be lost during sample preparation due to conjugation with protein thiols, which are precipitated and discarded. We observe that only 32 ± 3% of SFN is recovered 2 h after spiking into fetal bovine serum. The SFN-glutathione conjugate prepared at 10 mM in 0.1% formic acid in water (pH 3) dissociated by approximately 95% to free SFN, highlighting the difficulty in preparing thiol metabolite standards. We used the alkylating agent iodoacetamide (IAA) to both release SFN from protein thiols and force the dissociation of SFN metabolites. This thiol-blocking method increased SFN percent recovery from serum from 32 to 94 ± 5%, with a 4.7 nM method limit of quantitation. Applying the method to clinical samples, SFN concentrations were on average 6 times greater than when IAA was omitted. The IAA thiol-blocking method streamlines the analysis of bioavailable SFN in plasma samples.

High intensity muscle stimulation activates a systemic Nrf2-mediated redox stress response.

High intensity exercise is a popular mode of exercise to elicit similar or greater adaptive responses compared to traditional moderate intensity continuous exercise. However, the molecular mechanisms underlying these adaptive responses are still unclear. The purpose of this pilot study was to compare high and low intensity contractile stimulus on the Nrf2-mediated redox stress response in mouse skeletal muscle. An intra-animal design was used to control for variations in individual responses to muscle stimulation by comparing a stimulated limb (STIM) to the contralateral unstimulated control limb (CON). High Intensity (HI - 100Hz), Low Intensity (LI - 50Hz), and Naïve Control (NC - Mock stimulation vs CON) groups were used to compare these effects on Nrf2-ARE binding, Keap1 protein, and downstream gene and protein expression of Nrf2 target genes. Muscle stimulation significantly increased Nrf2-ARE binding in LI-STIM compared to LI-CON (p = 0.0098), while Nrf2-ARE binding was elevated in both HI-CON and HI-STIM compared to NC (p = 0.0007). The Nrf2-ARE results were mirrored in the downregulation of Keap1, where Keap1 expression in HI-CON and HI-STIM were both significantly lower than NC (p = 0.008) and decreased in LI-STIM compared to LI-CON (p = 0.015). In addition, stimulation increased NQO1 protein compared to contralateral control regardless of stimulation intensity (p = 0.019), and HO1 protein was significantly higher in high intensity compared to the Naïve control group (p = 0.002). Taken together, these data suggest a systemic redox signaling exerkine is activating Nrf2-ARE binding and is intensity gated, where Nrf2-ARE activation in contralateral control limbs were only seen in the HI group. Other research in exercise induced Nrf2 signaling support the general finding that Nrf2 is activated in peripheral tissues in response to exercise, however the specific exerkine responsible for the systemic signaling effects is not known. Future work should aim to delineate these redox sensitive systemic signaling mechanisms.

Aerobic exercise training partially reverses the impairment of Nrf2 activation in older humans.

Nuclear factor erythroid-2-related factor 2 (Nrf2), is an inducible transcription factor that improves redox balance through stimulating antioxidant gene expression. In older humans the Nrf2 response to a single bout of acute exercise is blunted compared to young indicating impaired redox signaling. The purpose of this randomized controlled trial was to investigate if the signaling impairment could be reversed with exercise training in older men and women, while also comparing to young. Young (18-28y, n = 21) and older (≥60y, n = 19) men and women were randomized to 8-week aerobic exercise training (ET; 3 d/wk, 45 min/d) or a non-exercise control group (CON). Nrf2 nuclear localization, gene expression for NQO1, HO1, and GCLC, and GCLC protein were measured in PBMCs in response to acute exercise trial (AET; 30-min cycling at 70% VO2 peak pre- and post-intervention at 7 timepoints (Pre, +10 m, +30 m, +1 h, +4 h, +8 h, +24 h). Young had greater Nrf2 signaling response compared to older at pre-intervention (p = 0.05), whereas the older had significantly higher basal Nrf2 levels (p = 0.004). ET decreased basal Nrf2 expression compared to CON (p = 0.032) and improved the Nrf2 signaling response in both young and older (p < 0.05). The degree of restoration in Nrf2 signaling response was related to the degree of change in basal Nrf2 (p = 0.039), which was driven by older adults (p = 0.014). Lower basal nuclear Nrf2 levels were associated with changes seen in AET responses for Nrf2 and GCLC protein, as well as NQO1 and GCLC mRNA. Together these data demonstrate that exercise training improves Nrf2 signaling and downstream gene expression and that lower basal Nrf2 levels are associated with a more dynamic acute response. Our results provide evidence that the impaired Nrf2 signaling in sedentary older adults can be restored to a degree with moderate exercise training, albeit not to the level seen in young. CLINICALTRIALS.GOV ID: NCT03419988.

The Stair Climb Power Test as an Efficacy Outcome in Randomized Trials of Function Promoting Therapies in Older Men.

BACKGROUND: Standardization of performance-based physical function measures that are reliable and responsive to intervention is necessary for efficacy trials of function promoting anabolic therapies (FPTs). Herein, we describe a standardized method of measuring stair climbing power (SCP) and evaluate its ability to assess improvements in physical function in response to an FPT (testosterone) compared to gait speed. METHODS: We used a 12-step SCP test with and without carrying a load (loaded, LSCP or unloaded, USCP) in two testosterone trials in older men. SCP was determined from mass, total step-rise, and time of ascent measured with an electronic timing system. Associations between SCP and leg press performance (strength and power), testosterone levels, and gait speed were assessed. Test-retest reliability was evaluated using interclass correlation and Bland-Altman analyses. RESULTS: Baseline SCP was negatively associated with age and positively with leg strength and power and gait speed. Both tests of SCP were safe and showed excellent reliability (intra-class correlation 0.91-0.97 in both cohorts). Changes in testosterone concentrations were associated with changes in USCP and LSCP, but not gait speed in mobility-limited men. Changes in leg press performance were associated with SCP in both trials. CONCLUSIONS: Both USCP and LSCP are safe and have high test-retest reliability. Compared to gait speed, SCP is associated more robustly with leg press performance and is sensitive to testosterone therapy. The LSCP might be a more responsive outcome than gait speed to evaluate the efficacy of FPT in randomized trials.

Long-Term Testosterone Supplementation in Older Men Attenuates Age-Related Decline in Aerobic Capacity.

Context: Testosterone increases skeletal muscle mass and strength, but long-term effects of testosterone supplementation on aerobic capacity, or peak oxygen uptake (V̇O2peak), in healthy older men with low testosterone have not been evaluated. Objective: To determine the effects of testosterone supplementation on V̇O2peak during incremental cycle ergometry. Design: A double-blind, randomized, placebo-controlled, parallel-group trial (Testosterone's Effects on Atherosclerosis Progression in Aging Men). Setting: Exercise physiology laboratory. Participants: Healthy men aged ≥ 60 years with total testosterone levels of 100 to 400 ng/dL (3.5 to 13.9 nmol/L) or free testosterone levels < 50 pg/mL (174 pmol/L). Interventions: Randomization to 1% transdermal testosterone gel adjusted to achieve serum levels of 500 to 950 ng/dL or placebo applied daily for 3 years. Main Outcome Measures: Change in V̇O2peak. Results: Mean (±SD) baseline V̇O2peak was 24.2 ± 5.2 and 23.6 ± 5.6 mL/kg/min for testosterone and placebo, respectively. V̇O2peak did not change in men treated with testosterone but fell significantly in men receiving placebo (average 3-year decrease, 0.88 mL/kg/min; 95% CI, -1.39 to 0.38 mL/kg/min; P = 0.035); the difference in change in V̇O2peak between groups was significant (average 3-year difference, 0.91 mL/kg/min; 95% CI, 0.010 to 0.122 mL/kg/min; P = 0.008). The 1-g/dL mean increase in hemoglobin (P < 0.001) was significantly associated with changes in V̇O2peak in testosterone-treated men. Conclusion: The mean 3-year change in V̇O2peak was significantly smaller in men treated with testosterone than in men receiving placebo and was associated with increases in hemoglobin. The difference in V̇O2peak change between groups may indicate attenuation of its expected age-related decline; the clinical meaningfulness of the modest treatment effect remains to be determined.

Effect of exercise intensity on Nrf2 signalling in young men.

INTRODUCTION: The transcription factor Nrf2 is the master regulator of antioxidant defence. Recent data indicate a single bout of moderate-intensity stationary cycling at a constant workload upregulates Nrf2 signalling in young, but not older men; however, the role of exercise intensity on Nrf2 activation has not been tested. We hypothesised that a high-intensity interval session would elicit a greater Nrf2 response than moderate aerobic exercise. METHODS: Nrf2 signalling in response to two 30-min cycling protocols (high-intensity interval and constant workload) was compared in young men (25 ± 1y, n = 16). Participants completed exercise trials in random order with blood collected pre-, immediately post-, and 30-mins post exercise. Five participants completed a control trial without any physical activity. Nrf2 signalling was determined by measuring protein expression of Nrf2 in whole cell and nuclear fractions. Plasma 8-isoprostanes as well as peripheral mononuclear cell glutathione reductase (GR) and superoxide dismutase activity were measured as markers of oxidative stress. RESULTS: The exercise trials elicited significant increases in nuclear Nrf2 (p < .01), but increases in whole cell Nrf2 did not reach statistical significance. GR activity and plasma 8-isoprostanes increased significantly in response to exercise (p < .05), and GR response was higher in the high-intensity trial (p < .05). CONCLUSION: Our findings indicate that acute aerobic exercise elicits activation of nuclear Nrf2, regardless of exercise intensity, but that higher-intensity exercise results in greater activity of GR. Future experiments should explore the effect of exercise mode and duration on Nrf2 signalling, and the role of intensity in compromised populations.

Preliminary evidence that age and sex affect exercise-induced hTERT expression.

The ability to repair cellular damage is reduced with aging, resulting in cellular senescence. Telomeres shorten as cells divide but the rate of telomere attrition is modulated by telomerase, an enzyme that adds nucleotides to the chromosome. Shelterin is a protein complex that acts as a negative regulator of telomerase. The aim of the present study was to investigate age-related differences in telomerase and shelterin responses to acute exercise. We hypothesized that acute exercise would stimulate an increased activity of telomerase (measured by telomerase reverse transcriptase, hTERT) without an increase in activity of shelterin (measured by telomeric repeat binding factor 2, TRF2) in both young and older individuals and that hTERT response would be attenuated in older individuals. Young (22±2y, n=11) and older (60±2y, n=8) men and women performed 30min of cycling. Blood was collected pre-exercise and 30, 60, and 90-min post-exercise. The trial induced a significant hTERT response in the cohort as a whole (p<0.05) with greater increases in the young as compared to the older group (time-by-group interaction p<0.05). As expected, TRF2 did not change in response to the trial, however older individuals had a higher TRF2 response at 60min (p<0.05). There was an unexpected sex difference, regardless of age, where men had significantly greater hTERT and TRF2 responses to the acute exercise as compared to women (p<0.05). These data support the hypothesis that aging is associated with attenuated telomerase activation in response to high-intensity exercise; however, this was only evident in men.

Effects of Testosterone Supplementation for 3 Years on Muscle Performance and Physical Function in Older Men.

Context: Findings of studies of testosterone's effects on muscle strength and physical function in older men have been inconsistent; its effects on muscle power and fatigability have not been studied. Objective: To determine the effects of testosterone administration for 3 years in older men on muscle strength, power, fatigability, and physical function. Design, Setting, and Participants: This was a double-blind, placebo-controlled, randomized trial of healthy men ≥60 years old with total testosterone levels of 100 to 400 ng/dL or free testosterone levels <50 pg/mL. Interventions: Random assignment to 7.5 g of 1% testosterone or placebo gel daily for 3 years. Outcome Measures: Loaded and unloaded stair-climbing power, muscle strength, power, and fatigability in leg press and chest press exercises, and lean mass at baseline, 6, 18, and 36 months. Results: The groups were similar at baseline. Testosterone administration for 3 years was associated with significantly greater performance in unloaded and loaded stair-climbing power than placebo (mean estimated between-group difference, 10.7 W [95% confidence interval (CI), -4.0 to 25.5], P = 0.026; and 22.4 W [95% CI, 4.6 to 40.3], P = 0.027), respectively. Changes in chest-press strength (estimated mean difference, 16.3 N; 95% CI, 5.5 to 27.1; P < 0.001) and power (mean difference 22.5 W; 95% CI, 7.5 to 37.5; P < 0.001), and leg-press power were significantly greater in men randomized to testosterone than in those randomized to placebo. Lean body mass significantly increased more in the testosterone group. Conclusion: Compared with placebo, testosterone replacement in older men for 3 years was associated with modest but significantly greater improvements in stair-climbing power, muscle mass, and power. Clinical meaningfulness of these treatment effects and their impact on disability in older adults with functional limitations remains to be studied.

Nrf2 mediates redox adaptations to exercise.

The primary aim of this review is to summarize the current literature on the effects of acute exercise and regular exercise on nuclear factor erythroid 2-related factor 2 (Nrf2) activity and downstream targets of Nrf2 signaling. Nrf2 (encoded in humans by the NFE2L2 gene) is the master regulator of antioxidant defenses, a transcription factor that regulates expression of more than 200 cytoprotective genes. Increasing evidence indicates that Nrf2 signaling plays a key role in how oxidative stress mediates the beneficial effects of exercise. Episodic increases in oxidative stress induced through bouts of acute exercise stimulate Nrf2 activation and when applied repeatedly, as with regular exercise, leads to upregulation of endogenous antioxidant defenses and overall greater ability to counteract the damaging effects of oxidative stress. The evidence of Nrf2 activation in response to exercise across variety of tissues may be an important mechanism of how exercise exerts its well-known systemic effects that are not limited to skeletal muscle and myocardium. Additionally there are emerging data that results from animal studies translate to humans.

Aerobic exercise increases resistance to oxidative stress in sedentary older middle-aged adults. A pilot study.

Older individuals who exercise regularly exhibit greater resistance to oxidative stress than their sedentary peers, suggesting that exercise can modify age-associated loss of resistance to oxidative stress. However, we recently demonstrated that a single bout of exercise confers protection against a subsequent oxidative challenge in young, but not older adults. We therefore hypothesized that repeated bouts of exercise would be needed to increase resistance to an oxidative challenge in sedentary older middle-aged adults. Sedentary older middle-aged men and women (50-63 years, n = 11) participated in an 8-week exercise intervention. Maximal oxygen consumption was measured before and after the intervention. The exercise intervention consisted of three sessions per week, for 45 min at an intensity corresponding to 70-85 % maximal heart rate (HRmax). Resistance to oxidative stress was measured by F2-isoprostane response to a forearm ischemia/reperfusion (I/R) trial. Each participant underwent the I/R trial before and after the exercise intervention. The intervention elicited a significant increase in maximal oxygen consumption (VO2max) (P < 0.0001). Baseline levels of F2-isoprostanes pre- and post-intervention did not differ, but the F2-isoprostane response to the I/R trial was significantly lower following the exercise intervention (time-by-trial interaction, P = 0.043). Individual improvements in aerobic fitness were associated with greater improvements in the F2-isoprostane response (r = -0.761, P = 0.011), further supporting the role of aerobic fitness in resistance to oxidative stress. These data demonstrate that regular exercise with improved fitness leads to increased resistance to oxidative stress in older middle-aged adults and that this measure is modifiable in previously sedentary individuals.

A Quasi Experiment to Determine the Effectiveness of a "Partially Flipped" versus "Fully Flipped" Undergraduate Class in Genetics and Evolution.

Two sections of Genetics and Evolution were taught by one instructor. One group (the fully flipped section) had the entire class period devoted to active learning (with background material that had to be watched before class), and the other group (the partially flipped section) had just a portion of class time spent on active learning (with the background material presented during class time). The same materials and assessments were used for both sections. Analysis of objective measures revealed that there was no significant difference between the learning outcomes of students in the two sections. There was no main effect of gender, major, or ethnicity on success in the whole cohort or in either section. There appeared to be a significant main effect of class standing, with freshmen performing significantly less well than sophomores, juniors, or seniors (who all performed equally well) in both sections (p < 0.01); however, this was a very preliminary observation, as there were very few freshmen in either section. The only predictor of success in the two sections was prior grade point average. An anonymous end-of-semester survey showed no significant difference between the two sections in interest in the subject matter.

Exercise-induced Nrf2-signaling is impaired in aging.

PURPOSE: The transcription factor nuclear erythroid-2 like factor-2 (Nrf2) is the master regulator of antioxidant defense. Data from animal studies suggest exercise elicits significant increases in Nrf2 signaling, and that signaling is impaired with aging resulting in decreased induction of phase II detoxifying enzymes and greater susceptibility to oxidative damage. We have previously shown that older adults have lower resistance to an oxidative challenge as compared to young, and that this response is modified with physical fitness and phytonutrient intervention. We hypothesized that a single bout of submaximal exercise would elicit increased nuclear accumulation of Nrf2, and that this response to exercise would be attenuated with aging. METHODS: Nrf2 signaling in response to 30-min cycling at 70% VO2max was compared in young (23±1y, n=10) and older (63±1, n=10) men. Blood was collected at six time points; pre-exercise, and 10min, 30min, 1h, 4h, and 24h post-exercise. Nrf2 signaling was determined in peripheral blood mononuclear cells by measuring protein expression by western blot of Nrf2 in whole cell and nuclear fractions, and whole cell SOD1, and HMOX, as well as gene expression (RT-PCR) of downstream Nrf2-ARE antioxidants SOD1, HMOX, and NQO1. RESULTS: Baseline differences in protein expression did not differ between groups. The exercise trial elicited significant increase in whole cell Nrf2 (P=0.003) for both young and older groups. Nuclear Nrf2 levels were increased significantly in the young but not older group (P=0.031). Exercise elicited significant increases in gene expression of HMOX1 and NQO1 in the young (P=0.006, and P=0.055, respectively) whereas gene expression in the older adults was repressed. There were no significant differences in SOD1 or HMOX1 protein expression. CONCLUSION: These findings indicate a single session of submaximal aerobic exercise is sufficient to activate Nrf2 at the whole cell level in both young and older adults, but that nuclear import is impaired with aging. Additionally we have shown repressed gene expression of downstream antioxidant targets of Nrf2 in older adults. Together these translational data demonstrate for the first time the attenuation of Nrf2 activity in response to exercise in older adults.

Brief quiet ego contemplation reduces oxidative stress and mind-wandering.

Excessive self-concern increases perceptions of threat and defensiveness. In contrast, fostering a more inclusive and expanded sense of self can reduce stress and improve well-being. We developed and tested a novel brief intervention designed to strengthen a student's compassionate self-identity, an identity that values balance and growth by reminding them of four quiet ego characteristics: detached awareness, inclusive identity, perspective taking, and growth. Students (N = 32) in their first semester of college who reported greater self-protective (e.g., defensive) goals in the first 2 weeks of the semester were invited to participate in the study. Volunteers were randomly assigned to one of three conditions: quiet ego contemplation (QEC), QEC with virtual reality (VR) headset (QEC-VR), and control. Participants came to the lab three times to engage in a 15-min exercise in a 30-days period. The 15-min QEC briefly described each quiet ego characteristic followed by a few minutes time to reflect on what that characteristic meant to them. Those in the QEC condition reported improved quiet ego characteristics and pluralistic thinking, decreases in a urinary marker of oxidative stress, and reduced mind-wandering on a cognitive task. Contrary to expectation, participants who wore the VR headsets while listening to the QEC demonstrated the least improvement. Results suggest that a brief intervention that reduces self-focus and strengthens a more compassionate self-view may offer an additional resource that individuals can use in their everyday lives.

Feasibility of Measuring Ventilatory Threshold in Adults With Stroke-Induced Hemiparesis: Implications for Exercise Prescription.

OBJECTIVES: To assess the feasibility of measuring ventilatory threshold (VT) in adults with walking impairments due to stroke. Secondary objectives are to assess reliability of VT over trials; assess whether participants could sustain treadmill walking at VT; and compare mean heart rate during sustained treadmill walking to estimated heart rate reserve (HRR). DESIGN: Cross-sectional, single-group design. SETTING: University research laboratory. PARTICIPANTS: Volunteer sample of adults (N=8) with impaired walking resulting from chronic stroke. INTERVENTIONS: Three submaximal treadmill walking tests on 3 separate days; a 30-minute treadmill walking session on a fourth day. MAIN OUTCOME MEASURES: Gas exchange variables were measured, and 2 independent observers identified VT. Mean heart rate response to treadmill walking at VT was measured and compared with estimated 40% of HRR. RESULTS: VT was measured successfully in 88% of all trials. There was no difference in VT among trials (P=.17). After multiple imputations to account for 3 missing data points, the intraclass correlation coefficient was .87 (95% confidence interval, .80-.95). All participants were able to walk for 20 minutes at VT. Mean ± SD heart rate during the session was 66.0%±8.0% of estimated maximal heart rate. There was no significant difference between mean heart rate and estimated HRR values (P=.70). CONCLUSIONS: In adults with impaired walking resulting from stroke, VT can be safely measured during submaximal treadmill walking. Participants were able to sustain walking at VT, and this value may provide an appropriate stimulus for aerobic exercise prescription in this population.

A tale of two sections: an experiment to compare the effectiveness of a hybrid versus a traditional lecture format in introductory microbiology.

Two sections of an introductory microbiology course were taught by one instructor. One was taught through a hybrid format and the other through a traditional format. Students were randomly assigned to the two sections. Both sections were provided with identical lecture materials, in-class worksheets, in-class assessments, and extra credit opportunities; the main difference was in the way the lecture material was delivered-online for the hybrid section and in person for the traditional section. Analysis of final grades revealed that students in the traditional section did significantly better than those in the hybrid section (p<0.001). There was a significant main effect of class standing (p<0.01). When performance in the two sections was compared for each class year separately, the differences were only significant for sophomores (p<0.001); freshmen, juniors, and seniors did not perform differently in the hybrid versus the traditional section. An anonymous midterm survey suggested factors likely contributing to the overall lower success of students in the hybrid section: some students in the hybrid section did not take lecture notes and/or use the audio component of the online lectures, suggesting minimal interaction with the lecture material for these students.

Acute exercise increases resistance to oxidative stress in young but not older adults.

A single bout of acute exercise increases oxidative stress and stimulates a transient increase in antioxidant enzymes. We asked whether this response would induce protection from a subsequent oxidative challenge, different from that of exercise, and whether the effects were affected by aging. We compared young (20 ± 1 years, n = 8) and older (58 ± 6 years, n = 9) healthy men and women. Resistance to oxidative stress was measured by the F2-isoprostane response to forearm ischemia/reperfusion (I/R) trial. Each participant underwent the I/R trial twice, in random order; once after performing 45 min of cycling on the preceding day (IRX) and a control trial without any physical activity (IRC). Baseline F2-isoprostane levels were significantly lower at IRX compared to IRC (P < 0.05) and not different between groups. F2-isoprostane response to IRX was significantly lower compared to IRC in young (P < 0.05) but not different in the older group. Superoxide dismutase activity in response to acute exercise was significantly higher in young compared to older adults (P < 0.05). These data suggest that signal transduction of acute exercise may be impaired with aging. Repeated bouts of transient reactive oxygen species production as seen with regular exercise may be needed to increase resistance to oxidative stress in older individuals.

Oxidative stress in older adults: effects of physical fitness.

Acute exercise results in transient change in redox balance. High concentrations of reactive oxygen species (ROS) can lead to oxidative damage to macromolecules. However, moderate periodic increases in ROS, such as experienced with habitual exercise, may activate signal transduction pathways which stimulate increases in endogenous antioxidant systems. This study tested the hypothesis that physically fit older adults would have less oxidative stress than unfit age-matched controls, due to greater circulating concentrations of non-enzymatic antioxidants and greater capacity to upregulate antioxidant enzymes. We compared 37 fit (mean age 65.2 ± 5 years) and 35 unfit (mean age 67.7 ± 4 years) men and women. Fitness status was classified by VO(2 max) and maximal leg power. Basal levels of oxidative stress were assessed by measuring urinary markers of nucleic acid damage and lipid peroxidation. Antioxidant status was assessed by measuring total antioxidant power and ratios of reduced to oxidized glutathione in plasma, at rest. The capacity to counteract an oxidative insult was assessed by measuring changes in plasma F(2)-isoprostanes in response to forearm ischemia-reperfusion. The fit individuals had significantly lower levels of urinary markers of oxidative damage (all P <0.05) and lower F(2)-isoprostane response to the oxidative challenge (P < 0.05), but there were no group differences in antioxidant status. The lower levels of oxidative stress in the fit individuals were not mediated by known effects of exercise training such as adiposity, HDL concentrations, or small molecular weight antioxidants. These data suggest that reduced oxidative stress associated with physical fitness results from differences in activity of antioxidant enzymes.

Tart cherry juice decreases oxidative stress in healthy older men and women.

Compared with young adults, older adults have significantly impaired capacities to resist oxidative damage when faced with acute stress such as ischemia/reperfusion. This impairment likely contributes to increased morbidity and mortality in older adults in response to acute trauma, infections, and the susceptibility to diseases such as atherosclerosis, cancer, diabetes, and Alzheimer's disease. Consumption of foods high in polyphenols, particularly anthocyanins, have been associated with improved health, but the mechanisms contributing to these salutary effects remain to be fully established. This study tested the hypothesis that consumption of tart cherry juice containing high levels of anthocyanins improves the capacity of older adults to resist oxidative damage during acute oxidative stress. In a double-blind, placebo-controlled, crossover design, 12 volunteers [6 men and 6 women; age 69 +/- 4 y (61-75 y)] consumed in random order either tart cherry juice or placebo (240 mL twice daily for 14 d) separated by a 4-wk washout period. The capacity to resist oxidative damage was measured as the changes in plasma F(2)-isoprostane levels in response to forearm ischemia-reperfusion (I/R) before and after each treatment. The tart cherry juice intervention reduced the I/R-induced F(2)-isoprostane response (P < 0.05), whereas placebo had no significant effect. The tart cherry juice intervention also reduced basal urinary excretion of oxidized nucleic acids (8-hydroxy-2'-deoxyguanosine, 8-hydroxyguanosine) (P < 0.05) but not urinary excretion of isoprostanes. These data suggest that consumption of tart cherry juice improves antioxidant defenses in vivo in older adults as shown by an increased capacity to constrain an oxidative challenge and reduced oxidative damage to nucleic acids.

Functional and physiological effects of yoga in women with rheumatoid arthritis: a pilot study.

CONTEXT: Stress, both psychological and physiological, has been implicated as having a role in the onset and exacerbations of rheumatoid arthritis (RA). OBJECTIVE: This study investigated whether neuroendocrine and physical function in women with RA can be altered through a yoga intervention. DESIGN: Exercise intervention. SETTING: University research conducted at a medical clinic. PARTICIPANTS: Sixteen independently living, postmenopausal women with an RA classification of I, II, or III according to the American College of Rheumatology functional classification system served as either participants or controls. INTERVENTION: The study group participated in three 75-minute yoga classes a week over a 10-week period. MAIN OUTCOME MEASURES: At baseline and on completion of the 10-week intervention, diurnal cortisol patterns and resting heart rate were measured. Balance was measured using the Berg Balance Test. Participants completed the Health Assessment Questionnaire (HIQ), a visual analog pain scale, and the Beck Depression Inventory. RESULTS: Yoga resulted in a significantly decreased HAQ disability index, decreased perception of pain and depression, and improved balance. Yoga did not result in a significant change in awakening or diurnal cortisol patterns (P = .12).

Ischemia/reperfusion unveils impaired capacity of older adults to restrain oxidative insult.

Age independently predicts poor outcome in a variety of medical settings, including sepsis, trauma, severe burns, and surgery. Because these conditions are associated with oxidative stress, we hypothesized that the capacity to constrain oxidative insult diminishes with age, leading to more extensive oxidative damage during trauma. To test this hypothesis, we used suprasystolic inflation of an arm blood pressure cuff to safely induce localized forearm ischemia/reperfusion (I/R) and quantified plasma F(2)-isoprostane (IsoP) levels in serial blood samples. Before I/R, IsoP levels were similar in young (20-33 years) and older adults (62-81 years). After I/R challenge, the magnitude and duration of increased IsoP levels was significantly greater in older adults. Because aging is associated with declining levels of sex hormones that contribute to the regulation of antioxidant enzyme expression, we then examined the response to I/R in older women receiving hormone replacement therapy and found that these women did not manifest the amplified IsoP response found in untreated older women. These findings demonstrate that aging impairs the ability to restrain oxidative damage after an acute insult, which may contribute to the increased vulnerability of older adults to traumatic conditions and establishes a useful method to identify effective interventions to ameliorate this deficiency.