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Recently, we showed that three months of resistance exercise significantly alters 18 canonical pathways related to chronic inflammation in PBMCs of older adults. In this exploratory sub-study, the aim is to explore whether resistance exercise enhances the PBMCs stress response by mimicking an acute infection through in vitro LPS stimulation. Women (≥65 years) were randomly divided into intensive strength training (IST), strength endurance training (SET), or flexibility training (as control group, CON) groups. PBMCs were isolated and cultured with and without LPS for 24 h. Their RNA was analyzed via targeted RNA sequencing of 407 inflammation-related genes, with relevant fold-changes defined as ≤0.67 or ≥1.5 (3 months vs. baseline). A pathway analysis using ingenuity pathway analyses identified significant pathways among 407 genes with p < 0.05 and z-scores of ≤-2 or ≥2. Fourteen women were included in the analyses. A total of 151 genes with a significant fold-change were identified. In the CON group, a less-pronounced effect was observed. Strength training altered 23 pathways in the LPS-stimulated PBMCs, none of which overlapped between the IST and SET groups. A balanced exercise program that includes both IST and SET could beneficially adapt the immune responses in older adults by inducing alterations in the inflammatory stress response of PBMCs through different genes and pathways.

Background: Chronic low-grade inflammatory profile (CLIP) is one of the pathways involved in type 2 diabetes (T2D). Currently, there is limited evidence for ameliorating effects of combined lifestyle interventions on CLIP in type 2 diabetes. We investigated whether a 13-week combined lifestyle intervention, using hypocaloric diet and resistance exercise plus high-intensity interval training with or without consumption of a protein drink, affected CLIP in older adults with T2D., Methods: In this post-hoc analysis of the PROBE study 114 adults (≥55 years) with obesity and type 2 (pre-)diabetes had measurements of C-reactive protein (CRP), pro-inflammatory cytokines interleukin (IL)-6, tumor-necrosis-factor (TNF)-α, and monocyte chemoattractant protein (MCP)-1, anti-inflammatory cytokines IL-10, IL-1 receptor antagonist (RA), and soluble tumor-necrosis-factor receptor (sTNFR)1, adipokines leptin and adiponectin, and glycation biomarkers carboxymethyl-lysine (CML) and soluble receptor for advanced glycation end products (sRAGE) from fasting blood samples. A linear mixed model was used to evaluate change in inflammatory biomarkers after lifestyle intervention and effect of the protein drink. Linear regression analysis was performed with parameters of body composition (by dual-energy X-ray absorptiometry) and parameters of insulin resistance (by oral glucose tolerance test)., Results: There were no significant differences in CLIP responses between the protein and the control groups. For all participants combined, IL-1RA, leptin and adiponectin decreased after 13 weeks (p = 0.002, p < 0.001 and p < 0.001), while ratios TNF-α/IL-10 and TNF-α/IL-1RA increased (p = 0.003 and p = 0.035). CRP increased by 12 % in participants with low to average CLIP (pre 1.91 ± 0.39 mg/L, post 2.13 ± 1.16 mg/L, p = 0.006) and decreased by 36 % in those with high CLIP (pre 5.14 mg/L ± 1.20, post 3.30 ± 2.29 mg/L, p < 0.001). Change in leptin and IL-1RA was positively associated with change in fat mass (β = 0.133, p < 0.001; β = 0.017, p < 0.001) and insulin resistance (β = 0.095, p = 0.024; β = 0.020, p = 0.001). Change in lean mass was not associated with any of the biomarkers., Conclusion: 13 weeks of combined lifestyle intervention, either with or without protein drink, reduced circulating adipokines and anti-inflammatory cytokine IL-1RA, and increased inflammatory ratios TNF-α/IL-10 and TNF-α/IL-1RA in older adults with obesity and T2D. Effect on CLIP was inversely related to baseline inflammatory status., Competing Interests: Declaration of competing interest JdV-vdB is an employee of Danone Nutricia Research. SW is an employee of the Netherlands Organisation for Applied Scientific Research (TNO), which is a not-for-profit research organisation collaborating in several public-private partnerships or business-to-business research projects that receive funding from companies. All other authors declare no conflicts of interest related to this research., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Ageing-related low-grade inflammation is suggested to aggravate sarcopenia and frailty. This systematic review investigates the influence that drugs with anti-inflammatory effects (AIDs) have on inflammation and skeletal muscle., Methods: PubMed and Web of Science were systematically screened for articles reporting the effects of AIDs on inflammation on one hand and on muscle mass and/or performance on the other., Results: Twenty-eight articles were included. These articles were heterogeneous in terms of the subjects studied, intervention components, setting, and outcome measures. Articles on older humans with acute inflammation showed evidence that celecoxib and piroxicam could reduce inflammation and improve performance and that ibuprofen improves exercise-induced muscle hypertrophy and gains in strength. In younger humans, only the effects of AIDs combined with exercise were investigated; no significant benefits of non-selective COX-inhibitors were reported, but improved strength gains with etanercept and reduced muscle soreness with celecoxib were noted. Indomethacin increased acute exercise-induced inflammation and reduced satellite cell differentiation in exercising muscle. Most articles did not systematically report occurrences of side effects., Conclusions: Although AIDs showed significant reduction in inflammation-induced muscle weakness in older hospitalised patients with acute inflammation, robust evidence is still lacking. When combined with exercise, AIDs presented a protective effect against age-related loss of muscle mass, thus enhancing muscle mass and performance. The mechanism regulating muscle strength and its mass seems to differ between individuals of old and young age. However, the effects seem drug-specific and dose-dependent and appear to be influenced by subjects' trainability and the clinical context. In addition, the balance between benefits and harm remains unclear., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Chronic inflammation and Advanced Glycation End products (AGE) are associated with sarcopenia. Decreased voluntary muscle activation and increased antagonist coactivation can contribute to age-related muscle weakness. The influence of chronic inflammation and AGE in these neuromuscular mechanisms is not clear. We studied whether a relation exists between circulating levels of inflammatory cytokines and AGEs as well as the interplay between agonist and antagonist muscle activation. We studied 64 community-dwelling old subjects, during a maximal isometric voluntary contraction (MVC) and a reaction-time (RT) test of the upper limb. Twenty-five circulating inflammatory biomarkers were determined. Linear regression showed significant relationships between chronic inflammation and six muscle activation parameters. MIP-1β showed a significant negative relation with antagonist coactivation (during MVC) and antagonist muscle activity during pre-movement time (PMT) and movement time (MT) (during RT). A higher level of pentosidine (AGE) was predictive for a longer PMT. We conclude that in older relatively healthy persons antagonist muscle activation is influenced by chronic inflammation, contributing to age-related muscle weakness. Our results also suggest a mechanical and inflammatory influence of pentosidine in upper limb slowing of movement. These findings show novel insight in underlying mechanisms of age-related muscle weakness., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Hospital-associated deconditioning due to a combination of illness and inactivity is a serious problem for elderly adults. Here we investigate whether persistence in inflammatory status affects changes in physical function during short-term hospitalization., Methods: This was a prospective observational study in elderly medical patients at a geriatric department. Measurements were obtained at admission and one week after admission and included de Morton Mobility Index (DEMMI) test, 30-second chair stand test (30-s CST), 4-m gait speed (4-m GST) test, handgrip strength, activity levels determined with ActivPALs, and concentrations of circulating C-reactive protein (CRP) from blood samples. Only patients with inflammation (C-reactive protein levels ≥10mg·L -1 ) at admission were included in this study. They were divided into those with continued inflammation (CI: CRP remained ≥10mg·L -1 ) and those that became non-inflammatory (BN: CRP decreased to <10mg·L -1 ) after one week of admission., Results: On admission 214 patients (67% female) with a median (IQR) age of 86 (81-91) years were categorized as inflammatory. There were no baseline differences in physical function between CI (n=138, 67% female) and BN (n=76, 68% female). DEMMI-score increased similarly in both groups (P<0.05). When normalized to days between tests, only changes in handgrip strength were significantly different between the CI- and BN-group (-0.05 [-0.27-0.28] vs. 0.16 [-0.10-0.41] kg·day -1 , respectively, P<0.01). There was a positive association between changes in CRP and length of hospital stay (r s =0.30, P<0.001)., Conclusion: Hospitalized geriatric patients admitted with inflammation showed only moderate improvement of general mobility during hospital stay, regardless of changes in their inflammatory status. However, handgrip strength increased only in those patients who became non-inflammatory during hospitalization., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Geriatric patients with acute infection show increased muscle weakness and fatigability but the relative contribution of central and peripheral factors is unclear. Hospitalised patients with acute infection (82±6years, N=10) and community-dwelling controls (76±6years, N=19) sustained a maximal voluntary isometric contraction of the M. Adductor Pollicis until strength dropped to 50% of its maximal value. Voluntary muscle activation (VA) was assessed before and at the end of the fatigue protocol using twitch interpolation method and muscle activity was monitored using surface electromyography. Twenty-five circulating inflammatory biomarkers were determined. At pre-fatigue, no significant difference in VA was found between groups. VA decreased to similar levels (~50%) at the end of the fatigue protocol with no association with inflammatory biomarkers. In geriatric patients, muscle activity decreased significantly (p<0.05) during the fatigue protocol, whereas it increased in the controls (time∗group interaction p<0.05). The decrease in muscle activity was significantly related to higher levels of inflammation. Although slower muscle contraction and relaxation were significantly related to higher levels of inflammation, no statistical differences were found between groups. Our results confirm that muscle activity is significantly altered in older patients with acute infection and that local processes are involved., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Little is known about the effects of resistance training (RT) on circulating cytokines in older adults. Also, dose-response relationships remain unclear. This study investigated the impact of RT at different external loads on circulating inflammatory mediators in older community-dwelling individuals., Methods: Fifty-six community-dwelling older (68 ± 5 years) volunteers were randomized to 12 weeks of supervised RT (×3/week) at either high-resistance training [8 males, 10 females, 2 × 10-15 repetitions at 80% 1 repetition maximum (RM)], low-resistance training (9 males, 10 females, 1 × 80-100 repetitions at 20% 1 RM), or mixed low-resistance training (9 males, 10 females, 1 × 60 repetitions at 20% 1 RM followed by 1 × 10-20 repetitions at 40% 1 RM). Serum was available from 51 out of 56 participants at baseline and after 12 weeks for determination of interleukin (IL)-6, IL-8, IL-10, IL-1β, soluble tumor necrosis factor receptor (sTNFR)1, granulocyte macrophage colony-stimulating factor, and IL-1 receptor antagonist (ra)., Results: Twelve weeks of RT significantly increased sTNFR1 from 2.48 ± 0.57 ng/mL to 2.58 ± 0.59 ng/mL (overall time-effect P = .033) and Log IL-8 from 0.38 ± 0.18 pg/mL to 0.53 ± 0.32 pg/mL (overall time-effect P = .007). No time X group interaction (P = .916) was observed. In males of the high-resistance training group, there was an increase in Log IL-8 (from 0.45 ± 0.16 pg/mL to 0.68 ± 0.19 pg/mL; P = .005) and IL-1ra (from 68.60 ± 24.12 pg/mL to 79.56 ± 29.07 pg/mL; P = .007). No significant changes were found for the other markers., Conclusions: Our results show that 12 weeks of supervised RT induced an overall significant increase of circulating IL-8 and sTNFR1, independently from the external load applied. We suggest that exercising until volitional fatigue is the main trigger for exercise-induced responses. However, training at high external load also increased anti-inflammatory IL-1ra in male participants, which might be beneficial in combating low-grade inflammation., (Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Aging is associated with a chronic low-grade inflammatory status that contributes to chronic diseases such as age-related muscle wasting, kidney disease, and diabetes mellitus. Since advanced glycation end products (AGEs) are known to be proinflammatory, this systematic review examined the relation between the dietary intake of AGEs and inflammatory processes. The PubMed and Web of Science databases were screened systematically. Seventeen relevant studies in humans or animals were included. The intervention studies in humans showed mainly a decrease in inflammation in subjects on a low-AGE diet, while an increase in inflammation in subjects on a high-AGE diet was less apparent. About half of the observational studies found a relationship between inflammatory processes and AGEs in food. When the results are considered together, the dietary intake of AGEs appears to be related to inflammatory status and the level of circulating AGEs. Moreover, limiting AGE intake may lead to a decrease in inflammation and chronic diseases related to inflammatory status. Most of the trials were conducted in patients with chronic kidney disease or diabetes, and thus additional studies in healthy individuals are needed. Further investigation is needed to elucidate the effects of lifetime exposure of dietary AGEs on aging and health., (© 2014 International Life Sciences Institute.)

In older persons, vitamin D insufficiency and a subclinical chronic inflammatory status frequently coexist. Vitamin D has immune-modulatory and in vitro anti-inflammatory properties. However, there is inconclusive evidence about the anti-inflammatory role of vitamin D in older subjects. Thus, we investigated the hypothesis of an inverse relationship between 25-hydroxyvitamin D (25(OH)D) and inflammatory markers in a population-based study of older individuals. After excluding participants with high-sensitivity C-reactive protein (hsCRP) ≥ 10 mg/dl and those who were on chronic anti-inflammatory treatment, we evaluated 867 older adults ≥65 years from the InCHIANTI Study. Participants had complete data on serum concentrations of 25(OH)D, hsCRP, tumor necrosis factor (TNF)-α, soluble TNF-α receptors 1 and 2, interleukin (IL)-1β, IL-1 receptor antagonist, IL-10, IL-18, IL-6, and soluble IL-6 receptors (sIL6r and sgp130). Two general linear models were fit (model 1-adjusted for age, sex, and parathyroid hormone (PTH); model 2-including covariates of model 1 plus dietary and smoking habits, physical activity, ADL disability, season, osteoporosis, depressive status, and comorbidities). The mean age was 75.1 ± 17.1 years ± SD. In model 1, log(25OH-D) was significantly and inversely associated with log(IL-6) (β ± SE = -0.11 ± 0.03, p = <0.0001) and log (hsCRP) (β ± SE = -0.04 ± 0.02, p = 0.04) and positively associated with log(sIL6r) (β ± SE = 0.11 ± 0.04, p = 0.003) but not with other inflammatory markers. In model 2, log (25OH-D) remained negatively associated with log (IL-6) (β ± SE = -0.10 ± 0.03, p = 0.0001) and positively associated with log(sIL6r) (β ± SE = 0.11 ± 0.03, p = 0.004) but not with log(hsCRP) (β ± SE = -0.01 ± 0.03, p = 0.07). 25(OH)D is independently and inversely associated with IL-6 and positively with sIL6r, suggesting a potential anti-inflammatory role for vitamin D in older individuals.

Purpose of Review: Age-related chronic low-grade inflammatory profile (CLIP) has been recognized as an important causative factor for sarcopenia. Here, we report the recent evidence concerning CLIP and sarcopenia., Recent Findings: Twenty-one studies were included (12 observational, five interventional studies and four randomized controlled trials). Observational studies strengthen the association between CLIP and sarcopenia in cross-sectional and longitudinal designs. Interleukin (IL)-6 and tumour necrosis factor-α are the most reported inflammatory parameters. Biopsy studies confirm the role of oxidative mechanisms, protein kinase B and nuclear factor kappa-light-chain-enhancer of activated B cells pathways and implicate stress response mechanisms and heat shock protein. Adipose tissue as source of inflammatory cytokines remains unclear and correction for fat mass is advisable in new research. Exercise interventions (both aerobic and resistance training) demonstrate beneficial effects on CLIP even in the absence of decreases in weight, BMI or fat mass. IL-6 is also released during exercise, in hormone-like fashion unrelated to inflammation, and exercise-induced IL-6 changes require careful interpretation. Soy supplementation in one study showed no influence on CLIP and no recent pharmacological trials were retrieved., Summary: Associations between CLIP and sarcopenia are observed quite consistently and underlying mechanisms become apparent. Exercise remains the mainstay intervention to lower CLIP and counter sarcopenia. More research is warranted to unravel the exact dose-response relationship.

Background: Inflammation is the main cause of disease-associated muscle wasting. In a previous single blind study we have demonstrated improved recovery of muscle endurance following celecoxib treatment in hospitalized geriatric patients with acute infection. Here we further evaluate NSAID treatment with piroxicam in a double blind RCT and investigate the role of cytokines and heat shock proteins (Hsp) with respect to muscle performance. We hypothesized that NSAID treatment would preserve muscle performance better than antibiotic treatment alone, by reducing infection-associated inflammation and by increasing expression of cytoprotective Hsp., Methods: Consecutive admissions to the geriatric ward were screened. 30 Caucasian patients, median age 84.5 years, with acute infection-induced inflammation and serum levels of CRP > 10 mg/L were included and randomized to active treatment with 10 mg piroxicam daily or placebo. Assessment comprised general clinical and biochemical parameters, 25 cytokines in serum, intra-and extracellular Hsp27 and Hsp70, Elderly Mobility Scale (EMS) scores, grip strength (GS), fatigue resistance (FR) and lean body mass (LBM). Patients were evaluated until discharge with a maximum of 3 weeks after treatment allocation., Results: EMS scores, FR and grip work (GW), a measure taking into account GS and FR, significantly improved with piroxicam, but not with placebo. Early decreases in IL-6 serum levels with piroxicam correlated with better muscle performance at week 2. Basal expression of Hsp27 in monocytes without heat challenge (WHC) was positively correlated with FR at baseline and significantly increased by treatment with piroxicam compared to placebo. Profound modifications in the relationships between cytokines or Hsp and changes in muscle parameters were observed in the piroxicam group., Conclusions: Piroxicam improves clinically relevant measures of muscle performance and mobility in geriatric patients hospitalized with acute infection-induced inflammation. Underlying mechanisms may include modifications in the cytokine network and increases in monocytic expression of cytoprotective Hsp27., Trial Registration Number: ISRCTN: ISRCTN96340690.

We have used a multiplex bead array assay to detect simultaneously 25 different circulating cytokines in 35 control subjects (young versus old) and 29 patients (young versus old) with acute infection. Intracellular PBMC levels of heat shock proteins (Hsp) were determined using flow cytometry. Levels of MIG and IL-6 were higher in the elderly normal subjects and patients, respectively, compared to their young counterparts. Hsp32, Hsp70 and Hsp90 were higher in elderly compared to young normal subjects. This difference disappeared for patients with inflammation who had increased levels of Hsp32, Hsp70 and Hsp90 compared to normal subjects. Most striking, a different pattern of association between cytokines and Hsp was noticed in healthy elderly subjects compared to the other groups of participants. It is concluded that age-related stress, possibly oxidative, which can down-regulate cytokine production with a concomitant up-regulation of Hsp production, could be involved in this differential pattern of association.

Background: Acute inflammation has a negative effect on the muscular system in elderly patients, compromising the outcome of the underlying disease., Objective: The aim of this study was to evaluate the effect of cyclooxygenase-2 (COX-2) inhibition on muscle performance and mobility in hospitalized elderly patients with acute inflammation of infectious origin., Methods: In this single-blind, controlled trial, consecutively hospitalized elderly patients (age > or = 70 years) with inflammation (C-reactive protein [CRP] levels > or =10 mg/L) due to acute infection were randomly assigned to receive 2 weeks of treatment with the COX-2-selective inhibitor celecoxib, acetaminophen, or no supplementary medication (control). The following variables were assessed at baseline and at 1 and 2 weeks' follow-up: muscle fatigue resistance (primary outcome measure); grip strength and mobility (secondary outcome measures); and levels of the acute-phase markers CRP, interleukin (IL)-1beta, IL-6, IL-10, tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor-beta (TGF-beta) as explanatory variables., Results: Forty-three consecutively hospitalized elderly patients (31 women, 12 men; mean [SD] age, 84 [6] years) were enrolled. Fourteen patients received celecoxib, 14 received acetaminophen, and 15 received no supplementary medication. The change in fatigue resistance was significantly different between groups (P = 0.021, Kruskal-Wallis chi-square test), with significantly greater improvement in patients receiving celecoxib compared with the acetaminophen and control groups (63% increase from baseline; P < 0.05). There were no significant between-group differences in changes in grip strength, mobility, IL-1beta, IL-6, TNF-alpha, or TGF-beta. The changes in levels of IL-10 differed significantly between groups (P = 0.020, Kruskal-Wallis chi-square test), with greater improvement in the celecoxib group compared with the acetaminophen group (P = 0.032)., Conclusion: The results of this study suggest that COX-2-selective inhibition has a beneficial effect on muscle fatigue resistance in hospitalized elderly patients with acute inflammation of infectious origin. However, until further trials are conducted, the use of COX-2-selective inhibitors for this indication is not recommended.

Background/Objectives: To investigate if intra-articular biomarkers relate to peripheral and central sensitization in patients with late-stage knee osteoarthritis (KOA). Methods: A total of 17 (6M, 11F) patients (aged 69 ± 10 years) were assessed for peripheral (pressure pain thresholds (PPT)) and central (temporal summation (TS) and conditioned pain modulation (CPM)) sensitization the day before total knee arthroplasty. Synovial fluid was collected during surgery and assayed for IL-6, IL-8, IL-10, TNF-α, CXCL-10, BDNF, NGF, CCL2, CCL5, VEGF, IL-1RI, MMP-1, MMP-7, IL-1β, and CXCL-9. Associations of biomarkers and their combinations reflecting chronic (CXCL-9) and acute ((CCL2×CXCL-10)/IL-10)) inflammation, cartilage degeneration (MMP-1×MMP-7), and neurotrophy (NGF×BDNF) with PPT, TS, and CPM were analyzed by bivariate correlations and by multiple linear regression analyses corrected for BMI, sex, and age. Results: The medial joint line and the superior medial joint region showed the lowest PPT. Higher acute inflammation related significantly to worse pressure tenderness at the superior medial joint region (R2 = 0.642; p = 0.010). Cartilage degeneration and chronic inflammation were associated with both absolute (R2 = 0.827; p = 0.001) and relative CPM (R2 = 0.882; p < 0.001). Acute inflammation and neurotrophy were related to relative TS at the m. tibialis anterior (R2 = 0.728; p = 0.02). Conclusions: This study demonstrates that increased levels of intra-articular biomarkers of acute inflammation are related to peripheral sensitization and that biomarkers of cartilage degeneration and chronic inflammation are associated with central sensitization. These results may be a stepping-stone toward a better understanding of the working mechanism of peripheral and central sensitization in KOA pain and the development of more targeted therapeutic interventions. [ABSTRACT FROM AUTHOR]

In stroke rehabilitation there is a growing body of evidence that not all patients have the same potential to recover. Understanding the processes that give rise to the heterogeneous treatment responses in stroke survivors will lay foundations for any conceivable advance in future rehabilitation interventions. This review was set out to shine new light on the debate of biomarkers in stroke rehabilitation by linking fundamental insights from biogerontological sciences to neurorehabilitation sciences. In particular, skeletal muscle changes and inflammation are addressed as two potential constructs from which biomarkers for stroke rehabilitation can be derived. Understanding the interplay between these constructs as well as their relation to recovery could enhance stroke rehabilitation in the future. The rationale for the selection of these constructs is three-fold: first, recent stroke literature emphasizes the importance of identifying muscle wasting (also called stroke-induced muscle wasting) in stroke patients, a concept that is widely investigated in geriatrics but less in the stroke population. Second, insights from transdisciplinary research domains such as gerontology have shown that inflammation has severe catabolic effects on muscles, which may impede rehabilitation outcomes such as gait recovery. Last, it has been proven that (high-intensity) muscle strengthening exercises have strong anti-inflammatory effects in a non-stroke population. Therefore, an evidence-based rationale is presented for developing research on individual changes of muscle and inflammation after a stroke. [ABSTRACT FROM AUTHOR]

Frailty is highly prevalent in old age and confers an important mortality risk. Although the causes of frailty are multiple, immunosenescence (IS)-predominantly driven by cytomegalovirus (CMV)-has been implicated in its pathophysiology. Thus far, research examining the association between IS and frailty states is sparse and equivocal. On the other hand, evidence is mounting in support of the view that frailty can be reversed, especially for those in the pre-frail stage. Therefore, we aimed to clarify the impact of CMV on IS and its relevance to pre-frailty. One hundred seventy-three persons aged 80 to 99 years were enrolled. Pre-frailty was defined according to Fried's criteria. Anti-CMV IgG and serum IL-6 were measured using Architect iSystem and Luminex, respectively. T-cell phenotypes were determined using flow cytometry. The prevalence of pre-frailty was 52.6%, increased with age (p = .001), and was greater in men than women (p = .044). No relationship was found between pre-frailty and positive CMV serology. Further, CMV-seropositivity was significantly associated with less naïve cells, more memory and senescence-prone phenotypes (all p < .001). After adjusting for potential confounders, only IL-6, age and sex were predictive of pre-frailty. We conclude that the presence of pre-frailty is independent from CMV infection in very old subjects. [ABSTRACT FROM AUTHOR]

Purpose: Suppressing inflammaging at an early stage in life via exercise might prevent chronic diseases later in life. The aim was to investigate the influence of resistance training at different external loads on inflammatory markers in healthy young adults.Methods: Serum was collected for basal levels of cytokines (IL-1beta, IL-6, IL-8, sTNFR1, IL-1RA, IL-10 and GM-CSF) before and after 9 weeks exercise from 36 young (22 ± 2 years) healthy subjects who were randomized to three times weekly supervised resistance training at either HImax (n = 12, 1 × 10-12 repetitions at 80% 1RM), LO (n = 12, 1 × 10-12 repetitions at 40% 1RM), or LOmax (n = 12, 1 × 10-12 repetitions at 40% 1RM preceded by 60 repetitions at 20-25% 1RM) respectively.Results: Overall, IL-8 increased (p < 0.001) and IL-6 decreased (p = 0.001) after training, but no significant time*group interaction was found (respectively, p = 0.283 and p = 0.058 for IL-8 and IL-6). When analyzed separately, IL-8 increased significantly in HImax (p = 0.022) and LOmax (p = 0.024); and IL-6 decreased significantly in LOmax (p = 0.009) and LO (p = 0.013). No significant overall time effect was observed for sTNFR1 and IL-1RA; however, in HImax sTNFR1 (p = 0.031) and IL-1RA (p = 0.014) increased significantly, but remained unchanged in LOmax and LO. IL-1beta, IL-10 and GM-CSF levels remained undetectable in most participants.Conclusions: Nine weeks of resistance training-irrespective of the external load-have beneficial effects on circulating IL-8 and IL-6. In addition, training at high external load increases the anti-inflammatory cytokines sTNFR1 and IL-1RA. The results of this study show that resistance training has anti-inflammatory effects in healthy young persons and that the response of the different inflammatory mediators depends on the magnitude of the external load. [ABSTRACT FROM AUTHOR]

Ageing is associated with a chronic low-grade inflammatory profile (CLIP). Physical exercise could circumvent the deleterious effects of CLIP by influencing circulating inflammatory mediators and neurotrophic growth factors. This study aimed at assessing whether 12 weeks of progressive strength training (PST) influences circulating brain-derived neurotrophic factor (BDNF), interleukin (IL)-6 and IL-10 in elderly individuals. Forty community-dwelling persons aged 62–72 years participated. Twenty participants were assigned to 12-week PST (70–80 % of maximal strength, three times per week). Matched control individuals (n = 20) maintained daily activity levels. Serum was collected for BDNF, IL-6 and IL-10 assay from all participants before and after 12 weeks (for PST subjects 24–48 h after the last training). In PST, muscle strength was significantly improved (+49 % for leg extension, p = 0.039), and basal IL-6 levels significantly reduced (p = 0.001), which remained unchanged in control (p = 0.117). No significant change in BDNF was observed in PST subjects (p = 0.147) or control (p = 0.563). IL-10 was below the detection limit in most subjects. Gender and health status did not influence the results. Our results show that after 12-week PST, muscle performance improved significantly, and basal levels of IL-6 were significantly decreased in older subjects. However, serum BDNF was not altered. The lack of an observable change in BDNF might be due to a short-lived BDNF response, occurring acutely following exercise, which might have been washed out when sampling. Furthermore, blood levels of BDNF may not reflect parallel increases that occur locally in the brain and muscle. These hypotheses need confirmation by further studies. [ABSTRACT FROM AUTHOR]

In older persons, vitamin D insufficiency and a subclinical chronic inflammatory status frequently coexist. Vitamin D has immune-modulatory and in vitro anti-inflammatory properties. However, there is inconclusive evidence about the anti-inflammatory role of vitamin D in older subjects. Thus, we investigated the hypothesis of an inverse relationship between 25-hydroxyvitamin D (25(OH)D) and inflammatory markers in a population-based study of older individuals. After excluding participants with high-sensitivity C-reactive protein (hsCRP) ≥ 10 mg/dl and those who were on chronic anti-inflammatory treatment, we evaluated 867 older adults ≥65 years from the InCHIANTI Study. Participants had complete data on serum concentrations of 25(OH)D, hsCRP, tumor necrosis factor (TNF)-α, soluble TNF-α receptors 1 and 2, interleukin (IL)-1β, IL-1 receptor antagonist, IL-10, IL-18, IL-6, and soluble IL-6 receptors (sIL6r and sgp130). Two general linear models were fit (model 1-adjusted for age, sex, and parathyroid hormone (PTH); model 2-including covariates of model 1 plus dietary and smoking habits, physical activity, ADL disability, season, osteoporosis, depressive status, and comorbidities). The mean age was 75.1 ± 17.1 years ± SD. In model 1, log(25OH-D) was significantly and inversely associated with log(IL-6) ( β ± SE = −0.11 ± 0.03, p = <0.0001) and log (hsCRP) ( β ± SE = −0.04 ± 0.02, p = 0.04) and positively associated with log(sIL6r) ( β ± SE = 0.11 ± 0.04, p = 0.003) but not with other inflammatory markers. In model 2, log (25OH-D) remained negatively associated with log (IL-6) ( β ± SE = −0.10 ± 0.03, p = 0.0001) and positively associated with log(sIL6r) ( β ± SE = 0.11 ± 0.03, p = 0.004) but not with log(hsCRP) ( β ± SE = −0.01 ± 0.03, p = 0.07). 25(OH)D is independently and inversely associated with IL-6 and positively with sIL6r, suggesting a potential anti-inflammatory role for vitamin D in older individuals. [ABSTRACT FROM AUTHOR]

Here, we investigate changes in inflammation-related gene-expression in peripheral mononuclear blood cells (PBMC) by strength training. A total of 14 women aged ≥65 years were randomized into 3 months of either 3×/week intensive strength training (IST: 3×10 rep at 80% 1RM), strength endurance training (SET: 2×30 reps at 40% 1RM) or control (CON: 3×30 sec stretching). Differentially expressed genes (fold change ≤0.67 or ≥1.5) were identified by targeted RNA-sequencing of 407 inflammation-related genes. A total of 98 genes (n = 61 pro-inflammatory) were significantly affected. IST and SET altered 14 genes in a similar direction and 19 genes in the opposite direction. Compared to CON, IST changed the expression of 6 genes in the same direction, and 17 genes in the SET. Likewise, 18 and 13 genes were oppositely expressed for, respectively, IST and SET compared to CON. Changes in gene expression affected 33 canonical pathways related to chronic inflammation. None of the altered pathways overlapped between IST and SET. Liver X Receptor/Retinoid X Receptor Activation (LXR/RXR) and Triggering Receptor Expressed On Myeloid Cells 1 (TREM1) pathways were enriched oppositely in both training groups. We conclude that three months IST and SET can induce changes in CLIP-related gene expression in PBMC, but by affecting different genes and related pathways. [ABSTRACT FROM AUTHOR]

Objectives: To validate muscle endurance estimation and to examine relationships with dependency and inflammation in elderly persons. Design: Cross sectional validation and explorative study. Setting: Hospitalized geriatric patients and community-dwelling controls. Participants: 91 elderly patients (aged 83±5 years), 100 elderly controls (aged 74±5 years) and 100 young controls (aged 23±3 years). Measurements: Grip strength (GS) was recorded continuously during sustained maximal contraction until exhaustion. Fatigue resistance (FR) was expressed as the time during which GS drops to 50% of its maximum. Grip work (GW) was estimated as GW=GS*0.75*FR, and compared to the measured GW. In the elderly participants, relationships (controlling for age and physical activity) of GS, FR, GW and GW corrected for body weight (GW/BW) with dependency (Katz-scale) and inflammation (circulating IL-6 and TNF-alpha) were analyzed. Results: Excellent correlation between estimated and measured GW was found (r=0.98, p<0.001). The method error coefficient of variance was 10% for all participants; 7% for all elderly and 8% for young controls. Better GS, FR, GW and GW/BW was significantly related with less dependency (all p<0.05 or p<0.01, except for FR in the male) and with lower circulating IL-6 (all p<0.05 or p<0.01, except for GS in both genders). Higher IL-6 was significantly related to worse dependency (p<0.01). No significant relationships with TNF-alpha were found. Conclusion: GW estimation is a valid parameter reflecting muscle endurance in elderly persons presenting diverse clinical conditions. GW is significantly related to both dependency and circulating IL-6, and is a promising outcome parameter in comprehensive geriatric assessment. [ABSTRACT FROM AUTHOR]

Background: Heat shock proteins (Hsp) are ubiquitously synthesised in virtually all species and it is hypothesised that they might have beneficial health effects. Recent studies have identified circulating Hsp as an important mediator in inflammation - the effects of low-grade inflammation in the aging process are overwhelming. While much is known about intracellular Hsp70, scant data exist on circulating Hsp70 in the aging context. Therefore, the objectives of this study were to investigate the effect of age and disease on circulating Hsp70 and, in particular, to evaluate the association between circulating Hsp70 and inflammatory parameters. Results: Serum Hsp70, Interleukin (IL) -10, IL-6 and Tumor Necrosis Factor (TNF) alpha concentrations were determined in 90 hospitalised geriatric patients (aged 83 ± 6 years) and in 200 community-dwelling control subjects (100 elderly, aged 74 ± 5 years, and 100 young, aged 23 ± 3 years). In the community-dwelling elderly, serum Hsp70 and IL-10 concentrations were significantly lower and IL-6 was significantly higher when compared to healthy young control subjects. Elderly patients presenting inflammation (CRP serum levels ≥5 mg/L) showed significantly (p = 0.007) higher Hsp70 values; and Hsp70 correlated positively (p < 0.001) with IL-6 and CRP, but not with TNF-alpha or IL-10. A significant association was also noted between Hsp70 levels and the degree of dependency and cognitive decline in geriatric patients. Conclusions: The present data provide new evidence that serum concentration of Hsp70 decreases with age in a normal population. Our study also shows that higher levels of Hsp70 are associated with inflammation and frailty in elderly patients. [ABSTRACT FROM AUTHOR]

Background: There is growing evidence for the significant involvement of inflammatory processes in the development of muscle wasting in old age. Therefore, any disease accompanied by inflammation can be threatening to the muscle function in geriatric patients.Methods: Sixty-three hospitalized geriatric patients (42 female, 21 male; mean age 84.2 +/- 5.7 years) were monitored weekly for muscle function (grip strength, fatigue resistance, shoulder extension strength, and hip extension strength) and for concentration of circulating C-reactive protein (CRP), fibrinogen, interleukin 6 (IL-6), and tumor necrosis factor-alpha alpha (TNF-alpha).Results: On the basis of circulating CRP and fibrinogen concentrations, 42 patients were categorized on admission as inflammatory and 21 as noninflammatory. Inflammatory patients presented significantly weaker grip strength, shoulder extension strength, and a worse fatigue resistance than did noninflammatory patients. These muscle functions were negatively correlated with the concentrations of circulating CRP and IL-6, but not with fibrinogen or TNF-alpha. In noninflammatory patients, the fatigue resistance improved significantly during the first week of hospitalization. In patients admitted with inflammation, no improvement of muscle function was observed. Patients who remained inflammatory for 2 weeks or more presented a significant worsening of fatigue resistance.Conclusions: Geriatric hospitalized patients presenting with inflammation show significantly worse muscle functions, which do not improve during hospitalization despite adequate treatment of the primary disease. Reduced strength and fatigue resistance are significantly related to the concentration of circulating CRP and IL-6. Standard treatment of the underlying illness and classic physical therapy are not sufficient to normalize the skeletal muscle strength and fatigue resistance in these hospitalized patients. [ABSTRACT FROM AUTHOR]

Inflammageing – characterized by age-related chronic low-grade inflammation is considered to be positively influenced by physical exercises. The aim of this systematic review is to provide an update of the most recent literature regarding exercise effects on the inflammatory profile in older adults. This review is an update of an earlier published literature review and was performed according to the NICE guidelines. Databases PubMed and Web-of-Science were systematically searched by two independent authors screening for papers published since 2016. Effect sizes of outcome parameters related to the inflammatory profile were calculated where possible. Twenty-three articles were included. Resistance training (RT) was the most investigated type of exercise (13 articles: 8 in healthy, 1 in frail and 4 in older adults with a specific condition or disease). Aerobic training (AT) was investigated in 8 articles, including 5 studies in older adults with a specific disease or condition. Combined resistance & aerobic training (CT) was investigated in 7 articles: 3 were in healthy, 1 in frail and 3 in older adults with a specific condition or disease. 1 study investigated the effects of Tai Chi in older adults with mild cognitive impairment. In frail older subjects, IGF-1 - sole marker investigated - significantly increased after 8 weeks RT and CT, whereas AT showed no significant effects compared to control. Most consistent exercise effects consisted in lowering of circulating levels of CRP, IL-6 and TNF-α; which seemed more prominent in healthy older adults compared to those with a specific disease or condition. None of the studies reported an exacerbation of inflammation following exercise and all studied exercise protocols were feasible and safe for older adults. Overall, significant anti-inflammatory effects of exercise in older persons were reported. Literature remains extremely scarce regarding the exercise-induced effects in frail older persons. Therefore, there is an urgent need for more studies focusing on the frail elderly. There is growing literature data on exercise interventions in older adults with a specific condition or disease; however, it appears more challenging to reduce inflammageing through exercise in these specific patient groups. Importantly, the exercise interventions performed in all studies appeared to be feasible and safe for older patients, thus the presence of a specific condition or disease should not be considered as a contra-indication to perform physical exercise. [ABSTRACT FROM AUTHOR]

Impaired motor function is a prominent characteristic of aging. Inflammatory processes and oxidative stress from advanced glycation end-products are related to impaired motor function and could plausibly be a contributing factor to the pathogenesis of paratonia, a specific motor disorder in people with dementia. Severe paratonia results in a substantial increase of a caretaker's burden and a decrease in the quality of life. The pathogenesis of paratonia is not well understood, and no effective interventions are available to combat it. Intensive glycaemic control, reducing oxidative stress, possibly combined with a low AGE diet and AGE targeting medication may be the key method for preventing advanced glycation end-product accumulation and reducing the inflammatory burden as well as possibly postponing or preventing paratonia. • Inflammatory processes from AGEs are related to paratonia. • AGE induced viscoelastic changes in muscle tissue might be responsible. • Glycaemic control could possibly be an effective way to address AGE accumulation and prevent paratonia. • This new perspective on paratonia is a beginning point for further research. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]