Chronic Inflammation Is Associated With Low Physical Function in Older Adults Across Multiple Comorbidities

Brinkley, Tina E.; Leng, Xiaoyan; Miller, Michael E.; Kitzman, Dalane W.; Pahor, Marco; Berry, Michael J.; Marsh, Anthony P.; Kritchevsky, Stephen B.; Nicklas, Barbara J.

doi:10.1093/gerona/gln038

Cited by 257 publications

(223 citation statements)

References 25 publications

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“…However, only those individuals aged 70-79 years who had completed the 7-year follow-up were included. These results could not be confirmed in more representative studies of the elderly (Verghese et al 2011;Brinkley et al 2009), including our findings (Legrand et al 2013). Despite the biological interactions, TNF-α was shown to be less stable than IL-6, and only weak correlations could be found between these markers (Verghese et al 2011) (Pearson r=0.12, p=0.012).…”

Section: Value Of Crp and Other Inflammatory Markerscontrasting

confidence: 79%

“…Consistent with our results, these previous studies reveal that increased IL-6 levels are independent of age, gender, race, body composition, and comorbidities associated with poorer physical function. Furthermore, Brinkley and coworkers showed, with standardized measures across multiple study populations, that these associations were consistent in individuals with chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), high cardiovascular risk, and selfreported disability (Brinkley et al 2009). …”

Section: Discussionmentioning

confidence: 99%

“…Due to the strong relationship between chronic inflammation and impaired functioning across numerous age-related diseases or health conditions (Brinkley et al 2009), various inflammatory biomarkers have been proposed as potential risk indicators for functional decline over time. Interleukin (IL)-6 in particular has consistently been associated with muscle mass, muscle strength, and physical impairment and shown to predict onset of disability in older persons.…”

Section: Introductionmentioning

confidence: 99%

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Interleukin-6 predicts short-term global functional decline in the oldest old: results from the BELFRAIL study

Adriaensen

Matheï

Vaes

et al. 2014

AGE

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The chronic inflammatory state at old age may contribute to the pathophysiology of or reflect chronic conditions resulting in loss of physical and mental functioning. Therefore, our objective was to examine the predictive value of a large battery of serum inflammatory markers as risk indicators for global functional decline and its specific physical and mental determinants in the oldest old. Global functional decline and specific aspects of physical and mental functional decline were assessed during an average of 1.66 years (±0.21) in a sample of 303 persons aged 80 years or older of the BELFRAIL study. Serum levels of 14 inflammatory proteins, including cytokines, growth factors, and acute phase proteins, were measured at baseline. Almost 20 % of the participants had a significant global functional decline over time. Interleukin (IL)-6 serum levels were uniquely positively associated with global functional decline, even after correcting for multiple confounders (odds ratio 1.51). Odds ratios for the individual aspects (physical dependency, physical performance, cognition, and depression) of functioning were lower, and composite scores of physical or mental decline were not significant. The proportion of global functional decline exhibited a dose-response curve with increasing levels of IL-6. Thus, IL-6 is an independent risk indicator for accelerated global functional decline in the oldest old. Our results suggest that simple serum levels of IL-6 may be very useful in short-term identification or evaluation of global functional status in the oldest old.

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Section: Value Of Crp and Other Inflammatory Markerscontrasting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Interleukin-6 predicts short-term global functional decline in the oldest old: results from the BELFRAIL study

Adriaensen

Matheï

Vaes

et al. 2014

AGE

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“…Contrary to the widely recognized role of chronic inflammation in driving sarcopenia and frailty (Brinkley et al 2009;Michaud et al 2013), we failed to confirm the detrimental effect of inflammatory biomarkers, even after taking into consideration the presence of chronic inflammatory conditions or immunosuppressant treatment, although this will need to be clarified in our Functional MBI (median, IQR) 100 (100-100) 100 (100-100) 0.534 100 (100-100) 100 (100-100) 0.746 iADL (median, IQR) 9 (9-9) 9 (9-9) 0.408 9 (9-9) 9 (9-9) 0.420 ongoing follow-up. Further, we failed to detect significant correlations between ABSI which is representative of adiposity and serum IL-6 levels.…”

Section: Discussionmentioning

confidence: 86%

Sex-specific differences in risk factors for sarcopenia amongst community-dwelling older adults

Tay

Ding

Leung

et al. 2015

AGE

140

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With considerable variation including potential sex-specific differential rate of skeletal muscle loss, identifying modifiable factors for sarcopenia will be pivotal to guide targeted interventions. This study seeks to identify clinical and biological correlates of sarcopenia in community-dwelling older adults, with emphasis on the role of anabolic and catabolic stimuli, and special reference to gender specificity. In this crosssectional study involving 200 community-dwelling and functionally independent older adults aged ≥50 years, sarcopenia was defined using the Asian Working Group for Sarcopenia criteria. Comorbidities, cognitive and functional performance, physical activity and nutritional status were routinely assessed. Biochemical parameters included haematological indices, lipid panel, vitamin D level, anabolic hormones [insulin-like growth factor-1 (IGF-1), free testosterone (males only)] and catabolic markers [inflammatory markers (interleukin-6, Creactive protein) and myostatin]. Multiple logistic regression was performed to identify independent predictors for sarcopenia. Age was associated with sarcopenia in both genders. Malnutrition conferred significantly higher odds for sarcopenia in women (OR=5.71, 95 % CI 1.13-28.84.44, p=0.035) while higher but acceptable range serum triglyceride was protective in men (OR=0.05, 95 % CI 0.00-0.52, p=0.012). Higher serum myostatin independently associated with higher odds for sarcopenia in men (OR=1.11, 95 % CI 1.00-1.24, p=0.041). Serum IGF-1 was significantly lower amongst female sarcopenic subjects, with demonstrable trend for protective effect against sarcopenia in multiple regression models, such that each 1 ng/ml increase in IGF-1 was associated with 1 % decline in odds of sarcopenia in women (p=0.095). Our findings support differential pathophysiological mechanisms for sarcopenia that, if corroborated, may have clinical utility in guiding sex-specific targeted interventions for community-dwelling older adults.

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“…Their immunolocalization increases in E 0 mice with age, whereas it was very low in control animals and in young (6 week old) E° mice. There is accumulating evidence that aging is associated with a pro-inflammatory shift in vascular phenotype (Csizar et al, 2007), kidney (Rodwell et al, 2004), liver (Coban et al, 2008) and heart (Brinkley et al, 2009). We must comment that the presence of IL-6 in epithelial cells could be odd, but this result is in agreement with other data suggesting its expression in progressive renal disease (Zhang et al, 2009) presented an increased expression of IL-6.…”

mentioning

confidence: 99%

Apolipoprotein E and its role in aging and survival

Bonomini

Filippini

Hayek

et al. 2010

Experimental Gerontology

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The study of biological aging has seen spectacular progress in the last decade and markers are increasingly employed for understanding physiological processes that change with age. Recently, it has been demonstrated that apolipoprotein E (apoE) has a major impact on longevity, but its mechanisms are still not fully understood. ApoE-deficient (E o ) mice have proved to be a very popular model for studying spontaneous hypercholesterolemia and the subsequent development of atherosclerotic lesions, but only limited data are available with regard to aging and aging changes.We used this murine model to better characterize the involvement of apoE in aging and to evaluate its role in the maintenance of normal organ morphology. Our results show that E 0 mice at different ages (6, 12, 20 weeks old) developed age-dependent morphological and biochemical alterations, including fibrosis (newly formed collagen), pro-inflammatory cytokine (IL-6 and iNOS), lipofuscin accumulation, and decrease of antioxidant enzymes (superoxide dismutase and catalase) in several organs (kidney, liver and heart). It is significant that the observed degenerative findings in E 0 mice at different ages (6, 12, 20 weeks old) were not identified in control mice (C57BL), at 6, 12 and 20 weeks of age. Consequently, since these mice showed enzymatic and structural alterations, normally linked to the age, such as increase of lipofuscin, pro-inflammatory cytokines and decrease of antioxidant enzymes, we can conclude that apoE is a useful player in studies of longevity and age-related diseases, such as inflammatory status and atherosclerosis that are known risk factors for functional decline and early mortality. Moreover, it is possible that apoE may also play a role in other pathological conditions including, for example, cancer, rheumatoid arthritis and macular degeneration.

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Chronic Inflammation Is Associated With Low Physical Function in Older Adults Across Multiple Comorbidities

Cited by 257 publications

References 25 publications

Interleukin-6 predicts short-term global functional decline in the oldest old: results from the BELFRAIL study

Interleukin-6 predicts short-term global functional decline in the oldest old: results from the BELFRAIL study

Sex-specific differences in risk factors for sarcopenia amongst community-dwelling older adults

Apolipoprotein E and its role in aging and survival

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