The role of microRNAs in regulating inflammation and exercise-induced adaptations in rheumatoid arthritis.

MicroRNAs (miRNAs) are endogenously generated single-stranded RNAs that play crucial roles in numerous biological processes, such as cell development, proliferation, differentiation, metabolism and apoptosis. They negatively regulate target gene expression by repressing translation of messenger RNA into a functional protein. Several miRNAs have been implicated in the development and progression of RA. They are involved in inflammatory and immune processes and are associated with susceptibility to RA and disease activity. They are also considered to be potential markers of disease activity or even therapeutic targets. Likewise, several miRNAs are affected acutely by exercise and regulate exercise-related adaptations in the skeletal muscle and cardiovascular system and aerobic fitness. Interestingly, some miRNAs affected by exercise are also important in the context of RA. Investigating these might increase our understanding of the effects of exercise in RA and improve exercise prescription and, potentially, disease management. In this review, we focus on the miRNAs that are associated with both RA and exercise and discuss their roles in (and potential interactions between) RA and exercise-induced adaptations.

Acute effects of exercise on pain symptoms, clinical inflammatory markers and inflammatory cytokines in people with rheumatoid arthritis: a systematic literature review.

Background: Exercise is advocated in the treatment of rheumatoid arthritis (RA). However, uncertainty around the acute effects of exercise on pain and inflammation may be stopping people with RA from exercising more regularly. Objectives: To determine the acute effects of exercise on pain symptoms, clinical inflammatory markers, and inflammatory cytokines in RA. Design: A systematic review of the literature. Data sources and methods: Five databases were searched (PubMed, Cochrane Library, CINAHL, Scopus and SPORTDiscus); inclusion criteria were studies with acute exercise, a definite diagnosis of RA and disease characteristics assessed by clinical function (i.e., disease activity score, health assessment questionnaire and self-reported pain), clinical markers associated with inflammation (i.e., c-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)), and inflammatory cytokines (i.e., interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α)). Results: From a total of 1544 articles, initial screening and full text assessment left 11 studies meeting the inclusion criteria. A total of 274 people were included in the studies (RA = 186; control = 88). Acute bouts of aerobic, resistance, and combined aerobic and resistance exercise did not appear to exacerbate pain symptoms in people with RA. Conclusion: Post-exercise responses for pain, clinical inflammatory markers and inflammatory cytokines were not different between people with or without RA. Exercise prescription was variable between studies, which limited between-study comparisons. Therefore, future investigations in people with RA are warranted, which combine different exercise modes and intensities to examine acute effects on pain symptoms and inflammatory markers. Registration: The PROSPERO international prospective register of systematic reviews - CRD42018091155.

Participation in physical activity decreased more in people with rheumatoid arthritis than the general population during the COVID-19 lockdown: a cross-sectional study.

The COVID-19 pandemic and social distancing restrictions have significantly reduced population-wide physical activity (PA) levels. However, the impact of the pandemic and relevant restrictions on PA participation, and any potential barriers to it, in people with rheumatoid arthritis (RA) are not clear. Furthermore, we are unsure if any such PA changes have affected their body weight, mental wellbeing, and/or quality of life (QoL). Thus, the aim of this study was to examine the impact of the lockdown on PA participation in people with RA, versus people without RA. Participants (n = 128; RA = 27, non-RA = 101) completed a self-administered online survey, which included questions on PA, body weight, mental wellbeing and QoL. PA participation during lockdown was significantly lower among RA versus non-RA participants (p < 0.001). Additionally, a similar profile of results was found where more RA participants vs non-RA participants reported reduced habitual PA (59% vs 33%) and increased body weight (59% vs 35%). Mental wellbeing scores were similarly low in both groups during lockdown (RA: 20.8 ± 4.2; non-RA: 22.2 ± 3.4, p = 0.080). Matched group comparisons identified similar trends to full sample analyses. In the first months of the lockdown, more people with RA reported decreased PA participation and increased body weight than their non-RA counterparts. Access to exercise equipment and facilities appears to be the main cause for these results. Looking beyond COVID-19, specific PA promotion for people with RA will be required to prevent a pandemic of inactivity.

Novel Essential Amino Acid Supplements Following Resistance Exercise Induce Aminoacidemia and Enhance Anabolic Signaling Irrespective of Age: A Proof-of-Concept Trial.

We investigated the effects of ingesting a leucine-enriched essential amino acid (EAA) gel alone or combined with resistance exercise (RE) versus RE alone (control) on plasma aminoacidemia and intramyocellular anabolic signaling in healthy younger (28 ± 4 years) and older (71 ± 3 years) adults. Blood samples were obtained throughout the three trials, while muscle biopsies were collected in the postabsorptive state and 2 h following RE, following the consumption of two 50 mL EAA gels (40% leucine, 15 g total EAA), and following RE with EAA (combination (COM)). Protein content and the phosphorylation status of key anabolic signaling proteins were determined via immunoblotting. Irrespective of age, during EAA and COM peak leucinemia (younger: 454 ± 32 µM and 537 ± 111 µM; older: 417 ± 99 µM and 553 ± 136 µM) occurred ~60-120 min post-ingestion (younger: 66 ± 6 min and 120 ± 60 min; older: 90 ± 13 min and 78 ± 12 min). In the pooled sample, the area under the curve for plasma leucine and the sum of branched-chain amino acids was significantly greater in EAA and COM compared with RE. For intramyocellular signaling, significant main effects were found for condition (mTOR (Ser2481), rpS6 (Ser235/236)) and age (S6K1 (Thr421/Ser424), 4E-BP1 (Thr37/46)) in age group analyses. The phosphorylation of rpS6 was of similar magnitude (~8-fold) in pooled and age group data 2 h following COM. Our findings suggest that a gel-based, leucine-enriched EAA supplement is associated with aminoacidemia and a muscle anabolic signaling response, thus representing an effective means of stimulating muscle protein anabolism in younger and older adults following EAA and COM.