Effects Of Exercise In Humans Research Articles

Direct assessment of leukocyte signalling and cytokine secretion reveals exercise intensity-dependent reductions in anti-inflammatory cytokine action.

Circulating interleukin (IL)-6 and IL-10 concentrations are widely used to evaluate the anti-inflammatory effects of exercise but do not capture cytokine action at the cellular level. Whether and how acute exercise impacts anti-inflammatory cytokine action in humans is unknown. To determine how exercise intensity and pattern impact IL-6 and IL-10 action in blood leukocytes, 16 active adults (eight males/eight females; age: 30±3years; body mass index: 22.8±2.3kg/m2; : 51±6mL/kg/min) completed a no-exercise control condition (CTL) or isocaloric bouts of cycling performed below (moderate continuous exercise; MCE) or above (heavy continuous or heavy intermittent exercise; HCE or HIE, respectively) lactate threshold. Venous blood (before, after, 30min after and 90min after exercise) was analysed for immune cell subpopulations, plasma cytokine concentrations, anti-inflammatory cytokine action and monocyte phenotype. Exercise induced rapid leukocytosis (P<0.001) and increased plasma IL-6 (P<0.001), IL-10 (P=0.0145) and tumour necrosis factor-⍺ (TNF-⍺) (P=0.0338) concentrations in an intensity-dependent manner (HCE and/or HIE vs. CTL). These systemic changes coincided with a diminished ability of IL-10/6 to phosphorylate STAT3 (P<0.001) and inhibit TNF-⍺ secretion (P=0.0238) in blood leukocytes following HCE and HIE. Monocyte polarization experiments revealed lower CD80 [MCE (P=0.0933) and HIE (P=0.0187) vs. CTL] and a tendency for higher CD163 expression (HCE vs. CTL, P=0.0985), suggesting that hyporesponsiveness to anti-inflammatory cytokine action does not impede the ability of exercise to promote an anti-inflammatory monocyte phenotype. These findings provide novel insights into the immunomodulatory effects of exercise in humans and highlight the importance of directly measuring cellular cytokine action when evaluating the anti-inflammatory effects of exercise. KEY POINTS: Circulating cytokine concentrations are frequently used to evaluate the anti-inflammatory effects of exercise but may not capture changes in cytokine action occurring at the cellular level. We directly assessed anti-inflammatory cytokine action - measured using a combination of intracellular signalling and cytokine secretion ex vivo - in distinct immune cell subpopulations after acute calorie-matched exercise bouts differing in intensity and pattern. Anti-inflammatory cytokine action was blunted following higher intensity exercise despite corresponding increases in circulating cytokine concentrations and immune cell counts. Changes in cytokine action were not explained by changes in cytokine receptor expression on circulating immune cells. Our findings provide new insights into the immunomodulatory effects of exercise in humans and highlight the importance of directly measuring cellular cytokine action when evaluating the anti-inflammatory effects of exercise.

Late-life voluntary wheel running reverses age-related aortic stiffness in mice: a translational model for studying mechanisms of exercise-mediated arterial de-stiffening.

Aortic stiffening, assessed as pulse-wave velocity (PWV), increases with age and is an important antecedent to, and independent predictor of, cardiovascular diseases (CVD) and other clinical disorders of aging. Aerobic exercise promotes lower levels of aortic stiffness in older adults, but the underlying mechanisms are incompletely understood, largely due to inherent challenges of mechanistic studies of large elastic arteries in humans. Voluntary wheel running (VWR) is distinct among experimental animal exercise paradigms in that it allows investigation of the physiologic effects of aerobic training without potential confounding influences of aversive molecular signaling related to forced exercise. In this study, we investigated whether VWR in mice may be a suitable model for mechanistic studies (i.e., "reverse translation") of the beneficial effects of exercise on arterial stiffness in humans. We found that 10weeks of VWR in old mice (~ 28months) reversed age-related elevations in aortic PWV assessed in vivo (Old VWR: 369 ± 19 vs. old sedentary: 439 ± 20cm/s, P < 0.05). The de-stiffening effects of VWR were accompanied by normalization of age-related increases in ex vivo mechanical stiffness of aortic segments and aortic accumulation of collagen-I and advanced glycation end products, as well as lower levels of aortic superoxide and nitrotyrosine. Our results suggest that late-life VWR in mice recapitulates the aortic de-stiffening effects of exercise in humans and indicates important mechanistic roles for decreased oxidative stress and extracellular matrix remodeling. Therefore, VWR is a suitable model for further study of the mechanisms underlying beneficial effects of exercise on arterial stiffness.

Gonadal hormones and voluntary exercise interact to improve discrimination ability in a set-shift task.

Exercise has been demonstrated to improve multiple facets of health, including cognitive function. Rodent studies have suggested that exercise has robust effects on the hippocampus and on tasks that require the hippocampus. However, studies of the effects of exercise in humans often focus on the benefits to cognitive processes that engage areas outside of the hippocampus, such as executive function. Additionally, when exercise's cognitive benefits are examined, consideration of both males and females, and gonadal hormones, is rarely made. Here we looked at the interaction of gonadal hormones and exercise in terms of the ability of male and female rats to learn to discriminate rewarded from unrewarded arms in a T maze based on either brightness (white vs. black) or texture (rough vs. smooth) and then to set-shift (a measure of executive function), where this required discrimination is based on the opposite dimension. Gonadectomized or intact males and females had access to running wheels for 2 weeks before being tested. Intact males and females given access to unlocked running wheels performed better at the initial discrimination (Set 1) compared with intact males and females with locked running wheels but not at the set shift (Set 2). No advantage of exercise was observed in gonadectomized rats.

Exercise for Better ALS Management?

Exercise for Better ALS Management?

Interview with Michael Ristow

Interview with Michael Ristow on his highly cited paper on his highly cited paper: Ristow M, Zarse K, Oberbach A, Klöting N, Birringer M, Kiehntopf M, Stumvoll M, Kahn CR, Bl?her M. "Antioxidants prevent health-promoting effects of physical exercise in humans". Proc Natl Acad Sci U S A. 2009 May 26; 106(21):8665-70. By January 2012, "Antioxidants prevent health-promoting effects of physical exercise in humans" was cited more than 177 times. At the time of the interview it was 125 times so it is ranked as number 5 among 100,000 papers on aging in 2009.

Not a fine wine: the ATP hypothesis may not get better with age

Not a fine wine: the ATP hypothesis may not get better with age

Antioxidants prevent health-promoting effects of physical exercise in humans

Antioxidants prevent health-promoting effects of physical exercise in humans

Antioxidants prevent health-promoting effects of physical exercise in humans

Exercise promotes longevity and ameliorates type 2 diabetes mellitus and insulin resistance. However, exercise also increases mitochondrial formation of presumably harmful reactive oxygen species (ROS). Antioxidants are widely used as supplements but whether they affect the health-promoting effects of exercise is unknown. We evaluated the effects of a combination of vitamin C (1000 mg/day) and vitamin E (400 IU/day) on insulin sensitivity as measured by glucose infusion rates (GIR) during a hyperinsulinemic, euglycemic clamp in previously untrained (n = 19) and pretrained (n = 20) healthy young men. Before and after a 4 week intervention of physical exercise, GIR was determined, and muscle biopsies for gene expression analyses as well as plasma samples were obtained to compare changes over baseline and potential influences of vitamins on exercise effects. Exercise increased parameters of insulin sensitivity (GIR and plasma adiponectin) only in the absence of antioxidants in both previously untrained (P < 0.001) and pretrained (P < 0.001) individuals. This was paralleled by increased expression of ROS-sensitive transcriptional regulators of insulin sensitivity and ROS defense capacity, peroxisome-proliferator-activated receptor gamma (PPARgamma), and PPARgamma coactivators PGC1alpha and PGC1beta only in the absence of antioxidants (P < 0.001 for all). Molecular mediators of endogenous ROS defense (superoxide dismutases 1 and 2; glutathione peroxidase) were also induced by exercise, and this effect too was blocked by antioxidant supplementation. Consistent with the concept of mitohormesis, exercise-induced oxidative stress ameliorates insulin resistance and causes an adaptive response promoting endogenous antioxidant defense capacity. Supplementation with antioxidants may preclude these health-promoting effects of exercise in humans.