Dermatomyositis (DM) is an autoimmune disease associated with enhanced type I interferon (IFN) signalling in skeletal muscle, but the mechanisms underlying muscle dysfunction and inflammation perpetuation remain unknown. Transcriptomic analysis of early untreated DM muscles revealed that the main cluster of down-regulated genes was mitochondria-related. Histochemical, electron microscopy, and in situ oxygraphy analysis showed mitochondrial abnormalities, including increased reactive oxygen species (ROS) production and decreased respiration, which was correlated with low exercise capacities and a type I IFN signature. Moreover, IFN-β induced ROS production in human myotubes was found to contribute to mitochondrial malfunctions. Importantly, the ROS scavenger N-acetyl cysteine (NAC) prevented mitochondrial dysfunctions, type I IFN-stimulated transcript levels, inflammatory cell infiltrate, and muscle weakness in an experimental autoimmune myositis mouse model. Thus, these data highlight a central role of mitochondria and ROS in DM. Mitochondrial dysfunctions, mediated by IFN-β induced-ROS, contribute to poor exercise capacity. In addition, mitochondrial dysfunctions increase ROS production that drive type I IFN-inducible gene expression and muscle inflammation, and may thus self-sustain the disease. Given that current DM treatments only induce partial recovery and expose to serious adverse events (including muscular toxicity), protecting mitochondria from dysfunctions may open new therapeutic avenues for DM.

This study explored mitochondrial capacities to oxidize carbohydrate and fatty acids and functional optimization of mitochondrial respiratory chain complexes in athletes who regularly train at high exercise intensity (ATH, n = 7) compared with sedentary (SED, n = 7). Peak O(2) uptake (Vo(2max)) was measured, and muscle biopsies of vastus lateralis were collected. Maximal O(2) uptake of saponin-skinned myofibers was evaluated with several metabolic substrates [glutamate-malate (V(GM)), pyruvate (V(Pyr)), palmitoyl carnitine (V(PC))], and the activity of the mitochondrial respiratory complexes II and IV were assessed using succinate (V(s)) and N,N,N',N'-tetramethyl-p-phenylenediamine dihydrochloride (V(TMPD)), respectively. Vo(2max) was higher in ATH than in SED (57.8 +/- 2.2 vs. 31.4 +/- 1.3 ml.min(-1).kg(-1), P < 0.001). V(GM) was higher in ATH than in SED (8.6 +/- 0.5 vs. 3.3 +/- 0.3 micromol O(2).min(-1).g dry wt(-1), P < 0.001). V(Pyr) was higher in ATH than in SED (8.7 +/- 1.0 vs. 5.5 +/- 0.2 micromol O(2).min(-1).g dry wt(-1), P < 0.05), whereas V(PC) was not significantly different (5.3 +/- 0.9 vs. 4.4 +/- 0.5 micromol O(2).min(-1).g dry wt(-1)). V(S) was higher in ATH than in SED (11.0 +/- 0.6 vs. 6.0 +/- 0.3 micromol O(2).min(-1).g dry wt(-1), P < 0.001), as well as V(TMPD) (20.1 +/- 1.0 vs. 16.2 +/- 3.4 micromol O(2).min(-1).g dry wt(-1), P < 0.05). The ratios V(S)/V(GM) (1.3 +/- 0.1 vs. 2.0 +/- 0.1, P < 0.001) and V(TMPD)/V(GM) (2.4 +/- 1.0 vs. 5.2 +/- 1.8, P < 0.01) were lower in ATH than in SED. In conclusion, comparison of ATH vs. SED subjects suggests that regular endurance training at high intensity promotes the enhancement of maximal mitochondrial capacities to oxidize carbohydrate rather than fatty acid and induce specific adaptations of the mitochondrial respiratory chain at the level of complex I.

Formerly considered as a passive process, the resolution of acute inflammation is now recognized as an active host response, with a cascade of coordinated cellular and molecular events that promotes termination of the inflammatory response and initiates tissue repair and healing. In a state of immune fitness, the resolution of inflammation is contained in time and space enabling the restoration of tissue homeostasis. There is increasing evidence that poor and/or inappropriate resolution of inflammation participates in the pathogenesis of chronic inflammatory diseases, extending in time the actions of pro-inflammatory mechanisms, and responsible in the long run for excessive tissue damage and pathology. In this review, we will focus on how resolution can be the target for therapy in “Th1/Th17 cell-driven” immune diseases and “Th2 cell-driven” immune diseases, with inflammatory bowel diseases (IBD) and asthma, as relevant examples. We describe the main cells and mediators stimulating the resolution of inflammation and discuss how pharmacological and dietary interventions but also life style factors, physical and psychological conditions, might influence the resolution phase. A better understanding of the impact of endogenous and exogenous factors on the resolution of inflammation might open a whole area in the development of personalized therapies in non-resolving chronic inflammatory diseases.

Interval aerobic training programs (IATP) improve cardiorespiratory and endurance parameters. They are, however, unsuitable to seniors as frequently associated with occurrence of exhaustion and muscle pain. The purpose of this study was to measure the benefits of an IATP designed with recovery bouts (IATP-R) in terms of cardiorespiratory and endurance parameters and its acceptability among seniors (≥70 years). Sedentary healthy volunteers were randomly assigned either to IATP-R or sedentary lifestyle. All participants performed an incremental cycle exercise and 6-minute walk test (6-MWT) at baseline and 9.5 weeks later. The first ventilatory threshold (VT ); maximal tolerated power (MTP); peak of oxygen uptake (VO ); maximal heart rate (HR ); and distance walked at 6-MWT were thus measured. IATP-R consisted of 19 sessions of 30-minute (6 × 4-min at VT + 1-minute at 40% of VT ) cycling exercise over 9.5 weeks. With an adherence rate of 94.7% without any significant adverse events, 9.5 weeks of IATP-R, compared to controls, enhanced endurance (VT : +18.3 vs -4.6%; HR at baseline VT : -5.9 vs +0.2%) and cardiorespiratory parameters (VO : +14.1 vs -2.7%; HR : +1.6 vs -1.7%; MTP: +19.2 vs -2.3%). The walk distance at the 6-MWT was also significantly lengthened (+11.6 vs. -3.1%). While these findings resulted from an interim analysis planned when 30 volunteers were enrolled in both groups, IATP-R appeared as effective, safe, and applicable among sedentary healthy seniors. These characteristics are decisive for exercise training prescription and adherence.