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INTRODUCTION: Muscle strengthening training (MST) and behavioural graded activity (BGA) show comparable effects on knee osteoarthritic (KOA) pain, but the mechanisms of action remain unclear. Both exercise-induced anti-inflammation and central sensitisation are promising pathways for pain relief in response to exercise therapy in patients with KOA: MST has the potential to decrease inflammation and BGA has the potential to decrease central sensitisation. Hence, this study aims to examine inflammation and central sensitisation as mediators for the effect of MST and/or BGA on pain in patients with KOA. METHODS AND ANALYSIS: The Knee OsteoArthritis PAIN trial started on 10 January 2020 (anticipated end: April 2024). The three-arm clinical trial aims to recruit 90 KOA patients who will be randomly allocated to 12 weeks of (1) MST, (2) BGA or (3) care as usual. Assessments will be performed at baseline, 13 and 52 weeks after finishing the intervention. Outcomes, including pain (Knee injury and Osteoarthritis Outcome Score), were chosen in line with the OARSI recommendations for clinical trials of rehabilitation interventions for OA and the IMMPACT/OMERACT recommendations for the assessment of physical function in chronic pain clinical trials. Inflammation as well as features of central sensitisation (including conditioned pain modulation, offset analgesia, temporal summation of pain and event-related potentials following electrical stimulation), will be considered as treatment mediators. A multiple mediators model will be estimated with a path-analysis using structural equation models. In July 2023, all 90 KOA patients have been included and 42 participants already finished the study. ETHICS AND DISSEMINATION: This study obtained ethics approval (B.U.N. 143201941843). Unravelling the mechanisms of action of exercise therapy in KOA will not only be extremely valuable for researchers, but also for exercise immunology and pain scientists and clinicians. TRIAL REGISTRATIO

Aims: This systematic review and meta-analysis evaluates the additional effect of exercise to hypocaloric diet on body weight, body composition, glycaemic control and cardio-respiratory fitness in adults with overweight or obesity and type 2 diabetes. Methods: Embase, Medline, Web of Science and Cochrane Central databases were evaluated, and 11 studies were included. Random-effects meta-analysis was performed on body weight and measures of body composition and glycaemic control, to compare the effect of hypocaloric diet plus exercise with hypocaloric diet alone. Results: Exercise interventions consisted of walking or jogging, cycle ergometer training, football training or resistance training and duration varied from 2 to 52 weeks. Body weight and measures of body composition and glycaemic control decreased during both the combined intervention and hypocaloric diet alone. Mean difference in change of body weight (−0.77 kg [95% CI: −2.03; 0.50]), BMI (−0.34 kg/m2 [95% CI: −0.73; 0.05]), waist circumference (−1.42 cm [95% CI: −3.84; 1.00]), fat-free mass (−0.18 kg [95% CI: −0.52; 0.17]), fat mass (−1.61 kg [95% CI: −4.42; 1.19]), fasting glucose (+0.14 mmol/L [95% CI: −0.02; 0.30]), HbA1c (−1 mmol/mol [95% CI: −3; 1], −0.1% [95% CI: −0.2; 0.1]) and HOMA-IR (+0.01 [95% CI: −0.40; 0.42]) was not statistically different between the combined intervention and hypocaloric diet alone. Two studies reported VO2max and showed significant increases upon the addition of exercise to hypocaloric diet. Conclusions: Based on limited data, we did not find additional effects of exercise to hypocaloric diet in adults with overweight or obesity and type 2 diabetes on body weight, body composition or glycaemic control, while cardio-respiratory fitness improved.

Nowadays, life expectancy is increasing but is not systematically accompanied by a decent quality of life during aging. With the overall aging of the population, it is urgent to highlight strategies to promote the maintenance of autonomy at old age. While the effects of exercise training on limiting the loss of functional autonomy in the elderly are well-established, the molecular mechanisms by which it may slowdown the hallmarks of skeletal muscle aging, notably through the regulation of telomere health and cellular senescence, need to be further investigated. In this thesis, we found that even if endurance training did not effectively reduce senescence, the training status might attenuate the senescence-associated secretory phenotype in human skeletal muscle. Moreover, the age-dependent increase in TERRA expression might represent a novel biological marker of aging which is alleviated by endurance training., (MOTR - Sciences de la motricité) -- UCL, 2022

Ageing is characterized by a low-grade chronic inflammation marked by elevated circulating levels of inflammatory mediators. This chronic inflammation occurring in the absence of obvious infection has been coined as inflammageing and represents a risk factor for morbidity and mortality in the geriatric population. Also, with ageing, important perturbations in the gut microbiota have been underlined and a growing body of literature has implicated age-related gut dysbiosis as contributing to a global inflammatory state in the elderly. Notwithstanding, very little attention has been given to how gut microbiota impact inflammageing. Here, we investigate the available evidence regarding the association between inflammageing and gut microbiota during ageing. PubMed, Web of Science and Scopus were systematically screened, and seven relevant articles in animals or humans were retrieved. The animal studies reported that Parabacteroides, Mucispirillum, Clostridium and Sarcina positively associate with the pro-inflammatory MCP-1 while Akkermansia, Oscillospira, Blautia and Lactobacillus negatively correlate with MCP-1. Furthermore, "aged"-type microbiota were associated with increased levels of IL6, IL-10, Th1, Th2, Treg, TNF-α, TGF-β, p16, SAMHD1, Eotaxin, and RANTES; activation of TLR2, NF-κB and mTOR; and with decreased levels of cyclin E and CDK2. On the other hand, the study on humans demonstrated that bacteria of the phylum Proteobacteria exhibited a positive correlation with IL-6 and IL-8, while Ruminococcus lactaris et rel. portrayed a negative correlation with IL-8. We conclude that changes in "aged"-type gut microbiota are associated with inflammageing., info:eu-repo/semantics/published

Aims Safety and tolerability of prolonged supplementation with a vitamin D, calcium and leucine-enriched whey protein medical nutrition drink (WP-MND) was evaluated in sarcopenic older adults. Methods A 13-week double-blinded, randomized, isocaloric placebo-controlled trial (PROVIDE study;n = 380) was extended with a voluntary 13-week open-label extension (OLE). OLE participants were randomized to receive daily 1 or 2 servings of WP-MND (21 g protein, 3 g leucine, 10 mu g vitD and 500 mg calcium per serving). Gastro-intestinal tolerability, kidney function and serum levels of calcidiol, parathyroid hormone (PTH) and calcium were evaluated at week 0, 13 and 26. Results and discussion In response to the high daily protein intake (median1.5; IQR: 1.3, 1.7 g/kg BW/day), the estimated glomerular filtration rate (eGFR) increased in the test group during the RCT (p = 0.013). The same trend was observed for those participants with moderate chronic kidney disease. During OLE no eGFR change was observed in any of the groups. Serum calcidiol and calcium reached a plateau after 13-week WP-MND supplementation. As expected, PTH significantly changed in the opposite direction, decreasing during RCT in the test group (T vs C:p < 0.001) and during OLE in former control groups. During RCT, 20/366 participants with normal baseline calcidiol reached levels >= 100 nmol/L (T:n = 18; C:n = 2) and 6 developed albumin-corrected calcium levels > 2.55 mmol/L (T:n = 3; C:n = 3), without associated adverse events. Conclusion A 6 months intervention with up to 2 servings of WP-MND did neither result in kidney function deterioration nor symptoms of vitamin D or calcium toxicity. The product was overall well tolerated.

Background: Fatigue resistance (FR) was here defined as the time during which grip strength (GS) drops to 50% of its maximum during sustained contraction. Since different GS systems exist, we compared FR obtained with Pneumatic (Pneu) and Hydraulic (Hydr) handgrip systems. Hand pain induced by both systems was also investigated since this might influence FR-outcomes. Methods: 618 young controls (Y: reference group), 426 middle-aged (MA) and 234 old community-dwelling adults (OLD), and 50 hospitalized patients (HOSP) participated. FR was recorded with Pneu and Hydr. Grip work corrected for body weight (area under the strength-time curve; GWBW = 0.75 ∗ maximal GS ∗ FR / body weight) was calculated. We corrected for body weight since heavier or more obese participants will have to engage more strength and sustain the effort over time. Thereafter GWBW was expressed as T-scores representing the deviation from the mean score of the sex-specific reference group. Experienced pain, its intensity and whether pain hindered participants to sustain the contraction were questioned. Results: Overall, although significant correlation between FR measured with both systems was found (r = 0.418, p < 0.001), FR measured by Pneu (55.7 ± 35.0 s) was higher compared to Hydr (34.2 ± 18.4 s). There was a proportional difference in FR measured with both systems (R2 = 0.36, p < 0.001), highlighting the longer participants could sustain FR test, the higher the difference in FR measured with both systems. Overall, there was no difference in pain variables between both systems. Independent of sex and system, GWBW deviated less from reference group in MA compared to OLD and HOSP. In OLD, GWBW deviated less from reference group than HOSP, independent of sex and system. Conclusion: Participants were unable to sustain the contraction with Hydr as long as with Pneu. Hydr seems less able to identify subjects with higher levels of muscle endurance. Based on the GWBM-scores we can conclude that either s, SCOPUS: ar.j, info:eu-repo/semantics/published

Advanced cancers are associated with a chronic inflammation, especially high interleukin-6 (IL-6) and with various levels of adipokines (leptin and adiponectin), while ghrelin counteracts the anorexigenic effect of leptin in cancer-induced anorexia-cachexia syndrome. We aimed to understand how IL-6, adipokines and ghrelin plasma levels could be influenced by cancer on the one hand, and by age, frailty, and nutritional status in old cancer patients on the other hand. Ninety-nine patients aged 79[76–83] years old were included. Sixty-six percent had advanced stages of cancer, and 34% had cachexia. Fifty percent were at risk of malnutrition, and 10% had overt malnutrition. None of the variables studied was significantly correlated with the advanced stage, or cachexia. In multiple regression, the only parameter significantly and positively associated with age was adiponectin (p = 0.008). Despite a high prevalence of frailty in our study, we did not find any independent association of frailty (assessed by G8) with IL-6, leptin, adiponectin, or ghrelin in multivariate analysis. We observed that a low albumin level was independently associated with a higher level of IL-6 (p < 0.0001), but not with the MNA score. However, leptin showed a positive correlation with BMI (p < 0.0001), confirming the persistence of a relationship between leptin and adiposity, even in older cancer patients. Finally, high IL-6 level was associated with a higher mortality rate (p = 0.027). In conclusion, IL-6, leptin, adiponectin, and ghrelin are not associated with advanced stages of cancer or cancer-induced cachexia in older subjects with cancer, but they are significantly correlated with anthropometric factors and body composition., SCOPUS: ar.j, info:eu-repo/semantics/published

Alterations in musculoskeletal health with advanced age contribute to sarcopenia and decline in bone mineral density (BMD) and bone strength. This decline may be modifiable via dietary supplementation. To test the hypothesis that a specific oral nutritional supplement can result in improvements in measures of bone health. Participants (n 380) were participants of the PROVIDE study, a 13-week, multicenter, randomized, controlled, double-blind, 2 parallel-group study among non-malnourished older participants (≥ 65 years) with sarcopenia [determined by Short Physical Performance Battery (SPPB; 0-12) scores between 4 and 9, and a low skeletal muscle mass index (SMI; skeletal muscle mass/BW × 100) ≤ 37% in men and ≤ 28% in women using bioelectric impedance analysis] Supplementation of a vitamin D, calcium and leucine-enriched whey protein drink that comprises a full range of micronutrients (active; 2/day) was compared with an iso-caloric control. Serum 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), biochemical markers of bone formation (osteocalcin; OC, procollagen type 1 amino-terminal propeptide; P1NP) and resorption (carboxy-terminal collagen crosslinks; CTX), insulin like growth factor 1 (IGF-1) and total-body BMD were analysed pre- and post-intervention. Serum 25(OH)D concentrations increased from 51.1 ± 22.9 nmol/L (mean ± SD) to 78.9 ± 21.1 nmol/L in the active group (p < 0.001 vs. control). Serum PTH showed a significant treatment difference (p < 0.001) with a decline in the active group, and increase in the control group. Serum IGF-1 increased in the active group (p < 0.001 vs. control). Serum CTX showed a greater decline in the active group (p = 0.001 vs. control). There were no significant differences in serum OC or P1NP between groups during the intervention. Total body BMD showed a small (0.02 g/cm2; ~ 2%) but significant increase in the active group after supplementation (p = 0.033 vs. control). Consuming a vitamin D, calcium and leucine

Background A chronic low-grade infammatory profle (CLIP) is associated with sarcopenia in older adults. Protein and Vitamin (Vit)D have immune-modulatory potential, but evidence for efects of nutritional supplementation on CLIP is limited. Aim To investigate whether 13 weeks of nutritional supplementation of VitD and leucine-enriched whey protein afected CLIP in subjects enrolled in the PROVIDE-study, as a secondary analysis. Methods Sarcopenic adults (low skeletal muscle mass) aged ≥ 65 years with mobility limitations (Short Physical Performance Battery 4–9) and a body mass index of 20–30 kg/m2 were randomly allocated to two daily servings of active (n=137, including 20 g of whey protein, 3 g of leucine and 800 IU VitD) or isocaloric control product (n=151) for a double-blind period of 13 weeks. At baseline and after 13 weeks, circulating interleukin (IL)-8, IL-1 receptor antagonist (RA), soluble tumor-necrosis-factor receptor (sTNFR)1, IL-6, high-sensitivity C-reactive protein, pre-albumin and 25-hydroxyvitamin(OH) D were measured. Data-analysis included repeated measures analysis of covariance (corrected for dietary VitD intake) and linear regression. Results IL-6 and IL-1Ra serum levels showed overall increases after 13 weeks (p=0.006 and p<0.001, respectively). For IL-6 a signifcant time × treatment interaction (p=0.046) was observed, with no signifcant change over time in the active group (p=0.155) compared to control (signifcant increase p=0.012). IL-8 showed an overall signifcant decrease (p=0.03). The change in pre-albumin was a signifcant predictor for changes in IL-6 after 13 weeks. Conclusions We conclude that 13 weeks of nutritional supplementation with VitD and leucine-enriched whey protein may attenuate the progression of CLIP in older sarcopenic persons with mobility limitations.

OBJECTIVES: The aim of this systematic review is to provide an overview of the efficacy of different exercise interventions to counter sarcopenia in older adults. This review will allow the Belgian Society of Gerontology and Geriatrics and other scientific societies to formulate specific exercise recommendations in their Clinical Guidelines for Sarcopenia. DESIGN: We used the method of a systematic umbrella-review. Based on the level of evidence, we formulated specific recommendations for clinical practice. METHODS: Two databases (Pubmed and Web Of Science) were searched systematically and methodological quality of the reviews was assessed. Extracted data was than mapped to an exercise category and an overall synthesis (bottom line statements) was formulated for each of these exercise categories. Subsequently, we assigned a rating of the quality of the evidence supporting each bottom line statement. RESULTS: We identified 14 systematic reviews or meta-analyses, encompassing four exercise categories: resistance training, resistance training + nutritional supplementation, multimodal exercise programmes and bloodflow restriction training. Importantly, very few systematic reviews or meta-analyses clearly mentioned baseline sarcopenia status. There is high quality evidence for a positive and significant effect of resistance training on muscle mass, muscle strength, and physical performance. The added effect of nutritional supplementation for resistance training on muscle function appears limited. Blood flow restriction training is a novel training method that has a significant impact on muscle strength. CONCLUSION: Since sarcopenia is affecting all skeletal muscles in the body, we recommend training the large muscle groups in a total body approach. Although low-intensity resistance training (≤50% 1RM) is sufficient to induce strength gains, we recommend a high-intensity resistance training program (i.e. 80% 1RM) to obtain maximal strength gains. Multimodal exercises and

Objectives: Previously, we developed and validated an easy test to measure muscle fatigability during sustained maximal handgrip contraction in older persons using a Martin Vigorimeter device. This study aimed at validating the equation to estimate grip work (GW) during sustained maximal handgrip contraction, by monitoring continuously the grip strength (GS) decay using a Jamar Dynamometer-like (JD) device. Design: Cross sectional, explorative study. Setting: Data collection took place at The National Research Centre for the Working Environment in Copenhagen, Denmark. Participants: 962 subjects, belonging to a subgroup of the Copenhagen Aging and Midlife Biobank, were enrolled. Methods: GS was recorded continuously during sustained maximal contraction until it dropped to 50% of its maximum and fatigue resistance (FR, time to fatigue) was noted. GW, area under the force-time curve, was compared to its estimate which was calculated as GWestimated=GSmax*0.75*FR. Results: Excellent correlation was found between GWestimated and GWmeasured (R2=0.98 p<0.001). The equation slightly overestimated GW by 6.04 kg*s (95% CI[-0.08, 12.15]) with a coefficient of variation method error of 6%. Conclusion: GW estimation is a valid parameter reflecting muscle work output during a sustained maximal grip effort in healthy middle-aged community-dwelling persons when using a JD. GW estimation is a promising outcome parameter in comprehensive geriatric assessment and its validation for commonly used instruments in geriatric practice will increase its clinical implementation.