Cross-sectional and Prospective Relationships of Interleukin-6 and C-Reactive Protein With Physical Performance in Elderly Persons: MacArthur Studies of Successful Aging
Abstract
BACKGROUND: Chronic inflammation has been proposed as a biological mechanism underlying the decline in physical function that occurs with aging. The purpose of this investigation was to examine the cross-sectional and prospective relationships between markers of inflammation, interleukin-6 (IL-6) and C-reactive protein (CRP), with several measures of physical performance in older persons aged 70 to 79 years. METHODS: Subjects were 880 high-functioning men and women participating in the MacArthur Study of Successful Aging (n = 1189), a subset of the Established Populations for Epidemiologic Studies of the Elderly (n = 4030). Plasma IL-6 and CRP levels were determined by enzyme-linked immunosorbent assay and log transformed to normalize the distributions. Physical function measures included handgrip strength, signature time, chair stands (time to complete five repetitions), and 6-m walk time. RESULTS: Women had lower (p < .05) IL-6 levels than men, but there was no significant difference between blacks and whites. IL-6 and CRP levels were higher (p < .05) in current smokers than in nonsmokers and in those with a greater body mass index (BMI). Hours per year undertaking moderate and strenuous physical activity were also related to inflammatory markers with higher (p < .001) IL-6 and CRP levels in less active individuals. After adjusting for age, sex, race, BMI, smoking status, use of nonsteroidal anti-inflammatory drugs, and prevalence of morbidity, those in the top two quartiles for walking speed had lower (p = .012) IL-6 levels than those in the bottom quartile. In addition, there was a trend (p = .038) for lower CRP levels in those with higher walking speed. CRP levels were also lower (p = .04) in individuals in the top quartile for grip strength. No significant differences were noted for chair stands or signature time performance. Repeat performance measures obtained on 405 subjects (67% of those eligible at baseline) obtained 7 years later had declined significantly (grip strength, 18%; signature time, 21%; walking speed, 31%; p < .001), except for the chair rise; however, baseline IL-6 and CRP were not associated with a change in performance. However, those who died or who were unable to undergo testing had higher baseline IL-6 and CRP levels (p < .01) and slower walking speed (p < .05). CONCLUSIONS: Although IL-6 has been shown to predict onset of disability in older persons and both IL-6 and CRP are associated with mortality risk, these markers of inflammation have only limited associations with physical performance, except for walking measures and grip strength at baseline, and do not predict change in performance 7 years later in a high-functioning subset of older adults.
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Higher plasma IL-6 levels are associated with adverse health habits: higher in smokers, less physical activity, impaired sleep, higher BMI.
“Other researchers have demonstrated that higher plasma IL-6 levels are associated with adverse health habits: values are higher in smokers than nonsmokers, in individuals who report less physical activity, in those whose sleep is impaired, and in those with a higher BMI, all behaviors that are adversely affected by stress (14, 34, 37, 50-52).”
From Chronic stress and age-related increases in the proinflammatory cytokine IL-6. (2003) · cites this paper as [50]
The Results and Cross-sectional Analyses report higher IL-6 in smokers, less physically active participants, and those with higher BMI. The paper studies a selected group of high-functioning older adults; our copy does not report an association with impaired sleep or establish that stress adversely affects these habits. (LLM, conf=0.90)
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BackgroundThe hypothalamic–pituitary–adrenal (HPA) axis in habitual smokers
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BackgroundInfluentialEffect of Cytotoxic Chemotherapy on Markers of Molecular Age in Patients With Breast Cancer
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“Cross-sectional studies have shown an association between low-grade systemic inflammation and physical inactivity in healthy subjects (Colbert et al., 2004; Kullo et al., 2007; Pedersen and Bruunsgaard, 2003; Taaffe et al., 2000).”
Exercise Training and Plasma C-reactive Protein and Interleukin-6 in the Elderly
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“Low grip-strength levels or a steep decline thus has associated with recently diagnosed rheumatoid arthritis (31), depressed mood (32), high insulin levels (33), and high levels of serologic markers for inflammation (interleukin 6, tumor necrosis factor a, and C-reactive protein) (34, 35).”
BackgroundBlood-brain barrier permeability and physical exercise
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Editorial: Something About Frailty
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“In the intervention group, the average CRP value decreased from 3.2 to 2.1 mg/L, and the changes in CRP, IL-6 and IL-18 were found to relate to changes in BMI.”
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“High plasma IL-6 levels were associated with self-reported mobility, activity of daily living (ADL) disability in communitydwelling elderly,(25) lower physical activity, and functional performance in high-functioning elderly persons.(26) Although IL-6 levels were not associated with subsequent changes in performance i…”
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“In addition to its tie to cardiovascular disease, chronic inflammation has been suggested as a key biological mechanism that may fuel declines in physical function leading to frailty, disability, and death.(9,13) For example, elevated plasma IL-6 levels indicated future disability in older adults, a finding that may r…”
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“Our observation of increased IL-6 levels in sarcopenia is supported by several analyses, in which correlations between reduced physical performance and increased levels of IL-6 and C-reactive protein (CRP) levels have been reported [8, 10, 11].”
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“Indeed, the health and aging literatures have focused on serum proinflammatory cytokine levels (Farzaneh-Far et al., 2009; Penninx et al., 2003; Taaffe et al., 2000).”
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“More globally, chronic inflammation has been suggested as one key biological mechanism that may fuel declines in physical function leading to frailty, disability, and, ultimately, death (30,46,47).”
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“The decreased IL-6 concentration in the VA group agrees with previous studies that have shown decreased levels of this cytokine in elderly individuals participating in a higher volume of moderate and strenuous physical activity (5,26).”
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“Numerous large cohort studies have consistently found lower levels of systemic inflammatory biomarkers in those who either subjectively reported higher levels of physical activity or objectively demonstrated greater aerobic fitness [185–190].”
Intramuscular fat and inflammation differ in older adults: The impact of frailty and inactivity
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“Older individuals with the highest levels of serum iL-6 experience decreased strength, impaired mobility, and an increased risk of death (10, 11, 39, 40).”
BackgroundSarcopenia and Age-Related Endocrine Function
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“In contrast, there were no longitudinal associations between inflammatory markers and changes in grip strength among high functioning elderly participants from the MacArthur Study of Successful Ageing [53].”
BackgroundPhysical Activity Status, But Not Age, Influences Inflammatory Biomarkers and Toll-Like Receptor 4
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“This finding supports previous reports by others which link hsCRP to physical activity (6,7).”
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“These inflammatory biomarkers, and others (such as erythrocyte sedimentation rate [ESR], albumin, and specific cytokines), have been shown to be predictors of mortality, in particular cardiovascular mortality (17), and to be associated with higher incidence and prevalence of clinicalmanifestation of CHD (18–23).”
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State of the Art Reviews: The Anti-Inflammatory Actions of Exercise Training
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Exercise Training as a Treatment for Chronic Inflammation in the Elderly
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“Although adiposity is a likely contributor, the relationship between inflammatory biomarkers and physical activity is independent of differential levels of obesity (as measured by BMI) in these studies.”
BackgroundInfluentialBiomarkers of Psychological Stress in Health Disparities Research
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Muscular Strength and Adiposity as Predictors of Adulthood Cancer Mortality in Men
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“0001 Lipids, mean (SD), mg/dL Total cholesterol 211 (44) 214 (41) 212 (51) 207 (40) <0.”
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Hostility and pain are related to inflammation in older adults
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Exercise and Biomarkers for Cancer Prevention Studies
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The relative influences of fitness and fatness on inflammatory factors
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“In a prospective trial of highly functioning septuagenarians, baseline IL-6 and CRP levels did not predict a change in performance measures over 7 years but did predict overall mortality.(15) Results from a study of >3000 septuagenarians indi-”
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- Authors
- Taaffe, D. R., Harris, T. B., Ferrucci, L., Rowe, J., & Seeman, T. E.
- Affiliations
- National Institutes of Health (US)
- University of California, Los Angeles (US)
- Venue
- The Journals of Gerontology Series A: Biological Sciences and Medical Sciences
- Publisher
- Oxford University Press (OUP)
- Published
- 2000-12-01
- Volume
- 55
- Issue
- 12
- Pages
- M709-M715
- ISSN
- 1079-5006 (ISSN-L)
- 1758-535X
- OpenAlex
- W2162034682
- Cited by
- 438
- References
- 40
- Citations by year
- 2026: 10 · 2025: 6 · 2024: 10 · 2023: 13 · 2022: 18 · 2021: 15 · 2020: 16 · 2019: 13 · 2018: 22 · 2017: 20 · 2016: 20 · 2015: 19 · 2014: 25 · 2013: 19 · 2012: 20
- FWCI
- 6.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journals of Gerontology Series A (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Keywords
- interleukin-6, C-reactive protein, chronic inflammation, physical performance, older adults, successful aging, grip strength, walking speed, chair stand, physical activity, smoking, body mass index, sex differences, mortality, functional decline, nonsteroidal anti-inflammatory drugs
- MeSH terms
- Aged, Aging, C-Reactive Protein, Cross-Sectional Studies, Female, Handwriting, Humans, Male, Physical Fitness, Prospective Studies, Time Factors, Interleukin-6, Walking, Hand Strength
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