Does metabolic reprogramming underpin age-associated changes in T cell phenotype and function?

T cells are required for an effective adaptive immune response. The principal function of T cells is to promote efficient removal of foreign material by identifying and mounting a specific response to nonself. A decline in T cell function in aging is thought to contribute to reduced response to infection and vaccination and an increase in autoimmunity. This may in part be due to the age-related decrease in naïve CD4+ T cells and increase in antigen-experienced CD4+ T cells, loss of redox homeostasis, and impaired metabolic switching. Switching between subsets is triggered by the integration of extracellular signals sensed through surface receptors and the activation of discrete intracellular metabolic pathways. This article explores how metabolic programming and loss of redox homeostasis during aging may contribute to age-associated changes in T cell phenotype and function. © 2014 Elsevier Inc.

Effects of short-term detraining on postprandial metabolism, endothelial function, and inflammation in endurance-trained men:dissociation between changes in triglyceride metabolism and endothelial function

Endurance-trained athletes experience a low level of postprandial lipaemia, but this rapidly increases with detraining. We sought to determine whether detraining-induced changes to postprandial metabolism influenced endothelial function and inflammation. Eight endurance-trained men each undertook two oral fat tolerance tests [blood taken fasted and for 6 h following a high-fat test meal (80 g fat, 80 g carbohydrate)]: one during a period of their normal training (trained) and one after 1 wk of no exercise (detrained). Endothelial function in the cutaneous microcirculation was assessed using laser Doppler imaging with iontophoresis in the fasted state and 4 h postprandially during each test. Fasting plasma triglyceride (TG) concentrations increased by 35% with detraining (P = 0.002), as did postprandial plasma (by 53%, P = 0.002), chylomicron (by 68%, P = 0.02) and very low-density lipoprotein (by 51%, P = 0.005) TG concentrations. Endothelial function decreased postprandially in both the trained (by 17%, P = 0.03) and detrained (by 22%, P = 0.03) conditions but did not differ significantly between the trained and detrained conditions in either the fasted or the postprandial states. These results suggest that, although fat ingestion induces endothelial dysfunction, interventions that alter postprandial TG metabolism will not necessarily concomitantly influence endothelial function.

Can the Q Link Ally,® a form of sympathetic resonance technology (SRT™), sttenuate scute mobile phone-related changes to neural function?

OBJECTIVES: Exposure to active mobile phones (MP) has been shown to affect human neural function as shown by the electroencephalogram (EEG). Although it has not been determined whether such effects are harmful, a number of devices have been developed that attempt to minimize these MP-related effects. One such device, the Q Link Ally® (QL; Clarus Products, International, L.L.C., San Rafael, CA), is argued to affect the human organism in such a way as to attenuate the effect of MPs. The present pilot study was designed to determine whether there is any indication that QL does alter MP-related effects on the human EEG. DESIGN: Twenty-four (24) subjects participated in a single-blind, fully counterbalanced crossover design in which subjects' resting EEG and phase-locked neural responses to auditory stimuli were assessed under conditions of either active MP or active MP plus QL. RESULTS: The addition of QL to the MP condition increased resting EEG in the gamma range and did so as a function of exposure duration, and it attenuated MP-related effects in the delta and alpha range (at trend-level). The addition of the QL also affected phase-locked neural responses, with a laterality reversal in the alpha range and an alteration to changes over time in the delta range, a reduction of the MP-related beta decrease over time at fronto-posterior sites, and a global reduction in the gamma range that increased as a function of exposure duration. No unambiguous relations were found between these changes and either performance or psychologic state. CONCLUSIONS: This pilot study suggests that the addition of the QL to active MP-exposure does affect neural function in humans, altering both resting EEG patterns and the evoked neural response to auditory stimuli, and that there is a tendency for some MP-related changes to the EEG to be attenuated by the QL.

Author response: can vascular function be assessed by the interpretation of retinal vascular diameter changes?

A protocol with repeated stimulation cycles should be analyzed stepwise, in that each stimulation is evaluated, and a reaction pattern is identified. No two subjects will react identically, in that dilation and recovery times can vary; however, this is not reason enough to abandon a multiple stimulation cycle with fixed recovery and stimulation times. Furthermore, it enables us to examine and determine the range in which a normal subject will be placed and can then be compared to different pathophysiological states (i.e., smokers and different diseases). The purpose of our paper was to highlight the importance of evaluating these different cycles and the danger of false interpretation when averaging results. There are many different ways of evaluating dilatory responses and elasticity, but each of them must be carefully evaluated and should not be overaveraged, which can result in a loss of sensitivity and specificity.

STRUCTURAL AND FUNCTIONAL CORRELATES OF EXERCISE VENTILATORY INEFFICIENCY IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE PATIENTS WITH MILD-TO-MODERATE SPIROMETRIC ABNORMALITIES

Background: Individuals with chronic obstructive pulmonary disease (COPD) have higher than normal ventilatory equivalents for carbon dioxide (VE/VCO2) during exercise. There is growing evidence that emphysema on thoracic computed tomography (CT) scans is associated with poor exercise capacity in COPD patients with only mild-to-moderate airflow obstruction. We hypothesized that emphysema is an underlying cause of microvascular dysfunction and ventilatory inefficiency, which in turn contributes to reduced exercise capacity. We expected ventilatory inefficiency to be associated with a) the extent of emphysema; b) lower diffusing capacity for carbon monoxide; c) a reduced pulmonary blood flow response to exercise; and d) reduced exercise capacity. Methods: In a cross-sectional study, 19 subjects with mild-to-moderate COPD (mean ± SD FEV1= 82 ± 13% predicted, 12 GOLD grade 1) and 26 age-, sex-, and activity-matched controls underwent a ramp-incremental symptom-limited exercise test on a cycle ergometer. Ventilatory inefficiency was assessed by the minimum VE/VCO2 value (nadir). A subset of subjects also completed repeated constant work rate exercise bouts with non-invasive measurements of pulmonary blood flow. Emphysema was quantified as the percentage of attenuation areas below -950 Housefield Units on CT scans. An electronic scoresheet was used to keep track of emphysema sub-types. Results: COPD subjects typically had centrilobular emphysema (76.8 ± 10.1% of total emphysema) in the upper lobes (upper/lower lobe ratio= 0.82 ± 0.04). They had lower peak oxygen uptake (VO2), higher VE/VCO2 nadir and greater dyspnea scores than controls (p<0.05). Lower peak O2 and worse dyspnea were found in COPD subjects with VE/VCO2 nadirs ≥ 30. COPD subjects had blunted increases in pulmonary blood flow from rest to iso-VO2 exercise (p<0.05). Higher VE/VCO2 nadir in COPD subjects correlated with emphysema severity (r= 0.63), which in turn correlated with reduced lung diffusing capacity (r= -0.72) and blunted changes in pulmonary blood flow from rest to exercise (r= -0.69) (p<0.01). Conclusions: Ventilation “wasted” in emphysematous areas is associated with reduced exercise ventilatory efficiency in mild-to-moderate COPD. Exercise ventilatory inefficiency links structure (emphysema) and function (gas transfer) to a key clinical outcome (reduced exercise capacity) in COPD patients with modest spirometric abnormalities.