Cross-sectional and Prospective Relationships of Interleukin-6 and C-Reactive Protein With Physical Performance in Elderly Persons: MacArthur Studies of Successful Aging

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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.