Association of inflammatory mediators with frailty status in older adults: results from a systematic review and meta-analysis

Marcos-Pérez, Diego; Sánchez-Flores, María; Proietti, Stefania; Bonassi, Stefano; Costa, Solange; Teixeira, João Paulo; Fernández‐Tajes, Juan; Pásaro, Eduardo; Laffón, Blanca; Valdiglesias, Vanessa

doi:10.1007/s11357-020-00247-4

Cited by 99 publications

(66 citation statements)

References 98 publications

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“…NLR, PLR and SII are proposed as inflammatory biomarkers. Inflammation is widely recognized to be associated with frailty, such as for other inflammatory markers like C-reactive protein, interleukin-6 and tumor necrosis factor α [ 31 – 33 ]. The potential mechanism may be that inflammation is associated with reduced synthesis and activity of insulin-like growth factor I (IGF-I), which is essential for muscle regeneration and the maintenance of muscle integrity [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Association of immunity markers with the risk of incident frailty: the Rugao longitudinal aging study

Zhang

Meng

et al. 2022

Immun Ageing

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Background The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) are readily available circulatory immunity markers that are associated with components of frailty. However, few studies have investigated the relationship between these immunity markers and frailty, and it remains unknown whether they are predictive of incident frailty in older adults in general. Hence, we aimed to examine the association of these immunity markers with the risk of incident frailty. Results Overall, 1822 older adults (mean age was 78.03 ± 4.46 years) were included in the Rugao Longitudinal Aging Study. NLR, PLR and SII were calculated from blood cell counts. The frailty definition was based on the Fried phenotype. At baseline, 200 (10.98%) individuals were defined as frailty, and no significant associations of NLR, PLR and SII with frailty were found. During the 2-year follow-up, 180 (15.67%) individuals were new-onset frailty. After adjustment, an increased logNLR (odds ratio [OR] 2.92, 95% confidence interval [CI] 1.20–7.18), logPLR (OR 2.54, 95% CI: 1.01–6.53) and logSII (OR 2.34, 95% CI: 1.16–4.78) were significantly associated with a higher risk of incident frailty in all individuals. Additionally, the associations of logNLR (OR 4.21, 95% CI 1.54–11.62 logPLR (OR 3.38, 95% CI: 1.17–9.91) and logSII (OR 2.56, 95% CI: 1.15–5.72) with incident frailty were remained after excluding individuals with comorbidities. In further analyzed, individuals with higher levels of NLR and SII had higher risk of incident frailty when we stratified individuals by quartiles of these immunity markers. Conclusion NLR and SII are easily obtained immunity markers that could be used to predict incident frailty in clinical practice.

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Section: Discussionmentioning

confidence: 99%

Association of immunity markers with the risk of incident frailty: the Rugao longitudinal aging study

Zhang

Meng

et al. 2022

Immun Ageing

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“…Aging is characterized by dysregulated immune [ 1 ] and metabolic homeostasis [ 2 , 3 ] where there is chronic sterile low-grade inflammation or inflammaging [ 4 ] that involves cellular senescence [ 5 , 6 ], immunosenescence [ 7 , 8 , 9 , 10 ], mitochondrial dysfunction [ 11 , 12 ], defective autophagy [ 13 , 14 ] and mitophagy [ 15 , 16 ], dysregulation of the ubiquitin–proteasome system [ 17 , 18 ], activation of the DNA damage response [ 19 , 20 ], meta-inflammation or metaflammation from chronic overnutrition or obesity [ 21 , 22 ], and gut microbiota dysbiosis [ 5 , 23 , 24 , 25 ]. These are reflected by changes in circulating immune markers including C-reactive protein (CRP) [ 26 ], interleukin-6 (IL-6) [ 27 ], tumor necrosis factor alpha (TNF-α) [ 28 ] and its soluble receptors (tumor necrosis factor receptor I (TNFR-I) and tumor necrosis factor receptor II (TNFR-II)) [ 28 ], vascular cell adhesion molecule I (VCAM-I) [ 29 ], d-dimer [ 30 ], and sirtuin signaling [ 31 , 32 ]. The drawback of chronic subclinical inflammation is that it is an essential risk factor for increasing the incidence of degenerative diseases such as AD [ 33 , 34 , 35 ].…”

Section: Introductionmentioning

confidence: 99%

Neuroinflammation in Alzheimer’s Disease

et al. 2021

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Alzheimer’s disease (AD) is a neurodegenerative disease associated with human aging. Ten percent of individuals over 65 years have AD and its prevalence continues to rise with increasing age. There are currently no effective disease modifying treatments for AD, resulting in increasingly large socioeconomic and personal costs. Increasing age is associated with an increase in low-grade chronic inflammation (inflammaging) that may contribute to the neurodegenerative process in AD. Although the exact mechanisms remain unclear, aberrant elevation of reactive oxygen and nitrogen species (RONS) levels from several endogenous and exogenous processes in the brain may not only affect cell signaling, but also trigger cellular senescence, inflammation, and pyroptosis. Moreover, a compromised immune privilege of the brain that allows the infiltration of peripheral immune cells and infectious agents may play a role. Additionally, meta-inflammation as well as gut microbiota dysbiosis may drive the neuroinflammatory process. Considering that inflammatory/immune pathways are dysregulated in parallel with cognitive dysfunction in AD, elucidating the relationship between the central nervous system and the immune system may facilitate the development of a safe and effective therapy for AD. We discuss some current ideas on processes in inflammaging that appear to drive the neurodegenerative process in AD and summarize details on a few immunomodulatory strategies being developed to selectively target the detrimental aspects of neuroinflammation without affecting defense mechanisms against pathogens and tissue damage.

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“…1H, p=0.00049, ρ=0.45) but not HAM/TSP patients (p=0.16). Among pro-inflammatory cytokines, IL-6 uniquely predicts global functional decline in aging[10] and inflammaging in a systematic review and meta-analysis[11]. Lifelong chronic infection with other latent viruses (CMV and HIV) causes long-term activation of the immune system over time, contributing to inflammaging[12].…”

Section: Resultsmentioning

confidence: 99%

Systemic cytokines and GlycA discriminate inflammaging, disease progression and corticosteroid response in HTLV-1-associated neuroinflammation

Assone

Menezes

Gonçalves

et al. 2021

Preprint

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Background: HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is an incapacitating neuroinflammatory disorder for which no disease-modifying therapy is available, but corticosteroids provide some clinical benefit. Objective: To investigate systemic cytokines and GlycA as possible biomarkers of immunopathogenesis and therapeutic response to corticosteroid pulse therapy in HAM/TSP. Methods: We prospectively followed 110 People living with HTLV-1 (PLwHTLV-1, 67 asymptomatic individuals and 43 HAM/TSP patients), for a total of 906 person-years. Plasma cytokine levels (IL-2/4/6/10/17A, IFN-γ, TNF) and GlycA were quantified by Cytometric Bead Array and 1NMR, respectively. Cytokine signaling and prednisolone response were validated in an independent cohort by nCounter digital transcriptomics. We applied logistic regression and machine learning algorithms to predict disease progression and glucocorticoid response. Results: IL-6 was positively correlated with age and GlycA in asymptomatics but not HAM/TSP patients. Systemic IFN-γ and IL-17A levels were increased in HAM/TSP patients, as compared to asymptomatics. All patients significantly decreased IL-17A levels post-treatment but only prednisolone-responders decreased IFN-γ levels post-treatment. Higher pre-treatment GlycA and TNF levels significantly predicted a negative therapeutic outcome, which was associated with higher post-treatment IFN-γ levels. Low IL-4 and IL-10 levels in incident HAM/TSP can be reverted to increased IL-10 and IL-4/IL-13 signaling by prednisolone in vitro. Conclusions: 1) An age-related increase in systemic IL-6/GlycA levels reveals inflammaging in PLwHTLV-1. 2) IFN-γ and IL-17A are biomarkers of untreated, active HAM/TSP disease, while pre-treatment GlycA and TNF predict therapeutic response to prednisolone pulse therapy. 3) Low IL-4/IL-10 and high IFN-γ signaling in incident HAM/TSP can be normalized by prednisolone.

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Association of inflammatory mediators with frailty status in older adults: results from a systematic review and meta-analysis

Cited by 99 publications

References 98 publications

Association of immunity markers with the risk of incident frailty: the Rugao longitudinal aging study

Association of immunity markers with the risk of incident frailty: the Rugao longitudinal aging study

Neuroinflammation in Alzheimer’s Disease

Systemic cytokines and GlycA discriminate inflammaging, disease progression and corticosteroid response in HTLV-1-associated neuroinflammation

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