Molecular inflammation: Underpinnings of aging and age-related diseases

Chung, Hae Young; Cesari, Matteo; Anton, Stephen D.; Marzetti, Emanuele; Giovannini, Silvia; Seo, Arnold Y.; Carter, Christy S.; Yu, Byung Pal; Leeuwenburgh, Christiaan

doi:10.1016/j.arr.2008.07.002

Cited by 1,050 publications

(876 citation statements)

References 191 publications

(194 reference statements)

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“…We observed a weak correlation between age and PR3 levels, but this association was in the positive direction, with the younger paediatric cases (aged 15 years) in our cohort showing lower PR3 levels than adults. This result is not unexpected, as chronic up-regulation of inflammatory mediators are associated with ageing [17]. Extrapolating from these data, we do not expect that younger T1D cases in our population are likely to display elevation in NETosis markers, although it cannot be ruled out, particularly for subjects with early-onset age and short disease duration.…”

Section: Discussionmentioning

confidence: 68%

NETosis-associated serum biomarkers are reduced in type 1 diabetes in association with neutrophil count

Qin¹,

Song²,

Speake³

et al. 2016

Clinical and Experimental Immunology

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1These authors contributed equally to this study. SummaryAs the immune pathways involved in the pathogenesis of type 1 diabetes (T1D) are not fully understood, biomarkers implicating novel mechanisms of disease are of great interest and call for independent evaluation. Recently, it was reported that individuals with T1D display dramatic elevations in circulating components of neutrophil extracellular traps (NETs), indicating a potential role for NETosis in T1D. Our aim was to evaluate further the potential of NET-associated proteins as novel circulating biomarkers in T1D. We tested serum from subjects with T1D (n 5 44) with a median age of 26Á5 years and a median duration of 2Á2 years, along with 38 age-matched controls. T1D subjects did not show elevations in either neutrophil elastase (NE) or proteinase 3 (PR3), as reported previously. In fact, both NE and PR3 levels were reduced significantly in T1D subjects, particularly in subjects within 3 years of diagnosis, consistent with the known reduction in neutrophil counts in recent-onset T1D. Indeed, levels of both NE and PR3 correlated with absolute neutrophil counts. Therefore, while not ruling out potential local or transient spikes in NETosis activity, the levels of these serum markers do not support a role for systemically elevated NETosis in the T1D population we studied. Rather, a modest reduction in these markers may reflect other important aspects of disease activity associated with reduced neutrophil numbers.

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Section: Discussionmentioning

confidence: 68%

NETosis-associated serum biomarkers are reduced in type 1 diabetes in association with neutrophil count

Qin¹,

Song²,

Speake³

et al. 2016

Clinical and Experimental Immunology

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“…n = 4; representative images are depicted. system (53) or altered redox homeostasis (54). Increased numbers of T cells and inflammatory macrophages also are observed in aged adipose tissue (44).…”

Section: Discussionmentioning

confidence: 99%

JAK inhibition alleviates the cellular senescence-associated secretory phenotype and frailty in old age

Tchkonia

Ding

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

638

519

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Chronic, low grade, sterile inflammation frequently accompanies aging and age-related diseases. Cellular senescence is associated with the production of proinflammatory chemokines, cytokines, and extracellular matrix (ECM) remodeling proteases, which comprise the senescence-associated secretory phenotype (SASP). We found a higher burden of senescent cells in adipose tissue with aging. Senescent human primary preadipocytes as well as human umbilical vein endothelial cells (HUVECs) developed a SASP that could be suppressed by targeting the JAK pathway using RNAi or JAK inhibitors. Conditioned medium (CM) from senescent human preadipocytes induced macrophage migration in vitro and inflammation in healthy adipose tissue and preadipocytes. When the senescent cells from which CM was derived had been treated with JAK inhibitors, the resulting CM was much less proinflammatory. The administration of JAK inhibitor to aged mice for 10 wk alleviated both adipose tissue and systemic inflammation and enhanced physical function. Our findings are consistent with a possible contribution of senescent cells and the SASP to age-related inflammation and frailty. We speculate that SASP inhibition by JAK inhibitors may contribute to alleviating frailty. Targeting the JAK pathway holds promise for treating age-related dysfunction.JAK/STAT pathway | cellular senescence | ruxolitinib | interleukin-6 | frailty

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“…Whereas the acute inflammatory process induced by infection or tissue injury is clear, considerably less is known about the deleterious effects of chronic low-grade inflammation. The oxidative stress-induced redox imbalance and the sustained upregulation of pro inflammatory mediators are believed to act as the patho-physiological basis underpinning inflammatory disorders including cardiovascular diseases, cancer, diabetes, dementia and also sarcopenia [1].…”

Section: Introductionmentioning

confidence: 99%

Inflammation and sarcopenia: A systematic review and meta-analysis

et al. 2017

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Nicola.Inflammation and sarcopenia: A systematic review and meta-analysis.Maturitas http://dx.doi.org/10.1016/j.maturitas. 2016.11.006 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Highlights Sarcopenia is associated with functional impairment and adverse outcomes.  Highly inflammatory cytokines are negatively related to muscle strength and mass.  Sarcopenia is associated with higher serum inflammatory parameters.  Chronic inflammation could play a role in sarcopenia. AbstractInflammatory cytokines have been shown to prompt muscle wasting, ultimately stimulating protein catabolism and suppressing muscle synthesis. However, the possible association between inflammatory parameters and sarcopenia is poorly understood. We therefore aimed to summarize the current evidence about this topic with a meta-analysis of studies reporting serum inflammatory parameters in patients with sarcopenia vs. people without sarcopenia (controls). An electronic PubMed and Scopus search through to 09/01/2016 and meta-analysis of cross-sectional studies comparing serum levels of inflammatory cytokines between patients with sarcopenia and controls was made, calculating random-effects standardized mean differences (SMDs) ±95% confidence intervals (CIs) as the effect size. Out of 1370 initial hits, 17 studies with a total of 11249 participants (3072 with sarcopenia and 8177 without) were meta-analysed. Sarcopenic participants had significantly higher levels of CRP (SMD=0.51; 95%CI 0.26, 0.77; p<0.0001; I 2 =96%) than controls. Conversely, serum IL6 levels were not significantly different (SMD=0.35; 95%CI: -0.19, 0.89; p=0.21; I 2 =97%) in people with sarcopenia versus controls. Sarcopenic people did not have higher levels of TNF-than controls (SMD=0.28; 95%CI -0.26, 0.83; p=0.31; I 2 =97%). In conclusion, sarcopenia seems to be associated with elevated serum CRP levels; future longitudinal studies are needed to clarify this relationship.

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Molecular inflammation: Underpinnings of aging and age-related diseases

Cited by 1,050 publications

References 191 publications

NETosis-associated serum biomarkers are reduced in type 1 diabetes in association with neutrophil count

NETosis-associated serum biomarkers are reduced in type 1 diabetes in association with neutrophil count

JAK inhibition alleviates the cellular senescence-associated secretory phenotype and frailty in old age

Inflammation and sarcopenia: A systematic review and meta-analysis

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