Cited by 440Nutrition and Health in AgingAdipokines, Inflammation, and Metabolic DiseasesExercise and Physiological Responses

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

Taaffe, D. R., Harris, T. B., Ferrucci, L., Rowe, J., Seeman, T. E.·2000·The Journals of Gerontology Series A: Biological Sciences and Medical Sciences

DOI 10.1093/gerona/55.12.m709

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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.

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“Table 1 summarises the data from 11 observational studies (2, 14-23) investigating the association between inflammatory mediators and physical activity or cardiorespiratory fitness as a surrogate measure of physical activity.”
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Locomotion, cognition and influences of nutrition in ageing
Ayers, E. I., & Verghese, J. (2013) · Proceedings of The Nutrition Society · doi:10.1017/s0029665113003716 · Cited by 20
Tea consumption and physical function in older adults: A cross-sectional study
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White blood cell counts, insulin resistance, vitamin D levels and sarcopenia in Korean elderly men
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Prediction of Incident Depression in Middle-Aged and Older Adults using Digital Gait Biomarkers Extracted from Large-Scale Wrist Sensor Data
Chan, L. L. Y., Brodie, M. A. D., & Lord, S. R. (2023) · Journal of the American Medical Directors Association · doi:10.1016/j.jamda.2023.04.008 · Cited by 19
Inflammatory markers and physical performance in middle-aged and older people in Indonesia
Sujarwoto, S., & Tampubolon, G. (2015) · Age and Ageing · doi:10.1093/ageing/afv052 · Cited by 19
Mechanisms Associating Physical Activity with Cancer Incidence
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Effect of the menopausal transition and physical activity energy expenditure on inflammatory markers: a MONET group study
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Association Between C-Reactive Protein and Relative Handgrip Strength in Postmenopausal Korean Women Aged 45–80 Years: A Cross-Sectional Study
Son, D., Song, S., & Lee, Y. (2022) · Clinical Interventions in Aging · doi:10.2147/cia.s356947 · Cited by 18
“Several previous studies have shown that elevated hs-CRP is related to low physical performance.(20,29) These findings suggest that chronic inflammation is involved in loss of physical performance, including muscle mass and strength.”
Method
Classification of pro-inflammatory status for interleukin-6 affects relative muscle strength in obese elderly women
Nascimento, D. D. C., de Sousa, N. M. F., Neto, I. V. D. S., Tibana, R. A., Souza, V. C., Vieira, D. C. L., Camarço, N. F., de Oliveira, S., de Almeida, J. A., Navalta, J. W., et al. (2015) · Aging Clinical and Experimental Research · doi:10.1007/s40520-015-0349-9 · Cited by 18
“Nonetheless, the results of the previous study [11, 12] corroborate with the current investigation, demonstrating that a higher pro-inflammatory status classified by IL-6 values certainly affects muscle strength in elderly women and that IL-6 is negatively associated with muscle strength and fat-free mass.”
BackgroundResult
Effects of aerobic exercise on functional capacity, anthropometric measurements and inflammatory markers in diabetic elderly women
dos Anjos, D. M. D. C., Moreira, B. D. S., Kirkwood, R. N., Dias, R. C., Pereira, D. S., & Pereira, L. S. M. (2016) · Journal of Bodywork and Movement Therapies · doi:10.1016/j.jbmt.2016.07.012 · Cited by 18
Editorial: Drugs, Aging, and the Future
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Physical functioning related to C-reactive protein and fibrinogen levels in mid-life women
Tomey, K., Sowers, M. R., Zheng, H. T., & Jackson, E. A. (2009) · Experimental Gerontology · doi:10.1016/j.exger.2009.10.002 · Cited by 17
“Research in the elderly suggests that chronically-elevated inflammatory response may compromise physical capacities, including strength, aerobic capacity, balance and coordination (Taaffe et al., 2000; Cesari et al., 2004; Davì et al., 2002).”
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Low haemoglobin levels contribute to low grip strength independent of low-grade inflammation in Japanese elderly women.
Yamada, E., Takeuchi, M., Kurata, M., Tsuboi, A., Kazumi, T., & Fukuo, K. (2015) · PubMed · doi:10.6133/apjcn.2015.24.3.11 · Cited by 17
“76 mg/L, respectively, in the aforementioned studies.(27-33) They were 22.”
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Physical Activity, Dietary Calorie Restriction, and Cancer
McTiernan, A. (2010) · Springer eBooks · doi:10.1007/978-1-4419-7551-5 · Cited by 17
Enhanced glucocorticoid sensitivity of cytokine release from circulating leukocytes stimulated with lipopolysaccharide in healthy male smokers
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“These inflammatory markers are also elevated in the blood of smokers (Bostrom et al., 1998; Harris et al., 1999; Taaffe et al., 2000; Zoppini et al., 2001) suggesting a link between smoking and systemic up-regulation of inflammation.”
Background
Physical exercise is associated with a reduction in plasma levels of fractalkine, TGF-β1, eotaxin-1 and IL-6 in younger adults with mobility disability
Kumar, P., Stiernborg, M., Fogdell‐Hahn, A., Månsson, K. N. T., Furmark, T., Berglind, D., Melas, P. A., Forsell, Y., & Lavebratt, C. (2022) · PLoS ONE · doi:10.1371/journal.pone.0263173 · Cited by 16
“Higher levels of IL-6 have been found to predict, or to be associated with, physical impairment, disability and mortality in older persons [13,15,17,47,48].”
Background
Relationship between monounsaturated fatty acids and sarcopenia: a systematic review and meta-analysis of observational studies
Alì, S., Corbi, G., Medoro, A., Intrieri, M., Scapagnini, G., & Davinelli, S. (2023) · Aging Clinical and Experimental Research · doi:10.1007/s40520-023-02465-0 · Cited by 18
“Additionally, in aging individuals, there is an elevation of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNFα), interleukin 6 (IL-6) and C-reactive protein (CRP), that contribute to low muscle mass and strength [46].”
Background
Circulating Interleukin-6 (but Not Other Immune Mediators) Associates with Criteria for Fried’s Frailty among Very Old Adults
Morais-Junior, G. S., Pérez, D. I. V., Furioso, A. C. T., Gomes, L., Silva, K. H. C. V. E., Alves, V. P., Moraes, C. F., & Nóbrega, O. D. T. (2020) · Journal of Aging Research · doi:10.1155/2020/6831791 · Cited by 16
“On our behalf, our report places a contribution by specifically investigating the subset of low-functioning very old adults, while most of the literature that evaluates immune mediators (intended as biomarkers for frailty) across performance levels simply addresses older individuals in general and usually includes hig…”
Background
Association between C-reactive protein (CRP) level and physical performance in community-dwelling elderly in Japan
Yoshida, Y., Iwasa, H., Kumagai, S., Yoshida, H., & Suzuki, T. (2009) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2009.10.002 · Cited by 16
“All rights reserved. doi:10.1016/j.archger.2009.10.002 associated with lower physical performance (Taaffe et al., 2000; Niu et al., 2008).”
Influential
Evaluation of humoral immune response to nosocomial pathogen and functional status in elderly patients with sepsis
Jeong, S. J., Yoon, S. S., Han, S. H., Yong, D., Kim, C. O., & Kim, J. M. (2013) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2013.07.001 · Cited by 16
State of the Art Reviews: Health Benefits Related to Exercise in Patients With Chronic Low-Grade Systemic Inflammation
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Elevated Circulating TNF-α in Fat-Free Mass Non-Responders Compared to Responders Following Exercise Training in Older Women
Fisher, G., Bickel, C., & Hunter, G. R. (2014) · Biology · doi:10.3390/biology3030551 · Cited by 15
“levels of inflammatory cytokines are associated with lower muscle mass and strength [16,17].”
Background
Midlife and late‐life diabetes and sarcopenia in a general older Japanese population: The Hisayama Study
Nakamura, K., Yoshida, D., Honda, T., Hata, J., Shibata, M., Hirakawa, Y., Furuta, Y., Kishimoto, H., Ohara, T., Chen, S., et al. (2021) · Journal of Diabetes Investigation · doi:10.1111/jdi.13550 · Cited by 16
Anti-inflammatory effects of exercise training. A systematic review
Onu, I., Iordan, D. A., Codreanu, C. M., Daniela, M., & Galaction, A. (2021) · Balneo and PRM Research Journal · doi:10.12680/balneo.2021.473 · Cited by 17
Serum Acute Phase Protein and Inflammatory Cytokine Network Correlations: Comparison of a Pre-Rheumatoid Arthritis and Non-Rheumatoid Arthritis Community Cohort
Masi, A. T., Rehman, A. A., Elmore, K. B., & Aldag, J. C. (2013) · Journal of Innate Immunity · doi:10.1159/000345700 · Cited by 15
Systemic Inflammation in Sarcopenia Alter Functional Capacity in Thai Community-dwelling Older People: A Preliminary Observational Study
Yuenyongchaiwat, K., & Akekawatchai, C. (2022) · Current Aging Science · doi:10.2174/1874609815666220513141300 · Cited by 14
“, slow gait speed, poor handgrip strength, low muscle mass) in the older people, such as lower muscle mass, decreased physical performance, and decreased muscle strength [18-20].”
Background
The mediating role of cytokine IL-6 on the relationship of FEV1 upon 6-minute walk distance in chronic obstructive pulmonary disease
Baldi, S., Bruschi, C., Maestri, R., Rezzani, A., Bellinzona, E., Fracchia, C., Pinna, G. D., Jose, P. E., Dacosto, E., Crotti, P., et al. (2014) · International Journal of COPD · doi:10.2147/copd.s57845 · Cited by 14
“33,34 The finding that the indirect effect of IL-6 on 6MWD diminishes in elderly COPD patients further reinforces the basis for speculating that cytokines also function as a defense reaction closely connected to the neuroendocrine dysregulation of aging, as previously reported in other research…”
Serum C-Reactive Protein Even at Very Low (<1.0 mg/l) Concentration Is Associated with Physical Performance in a Community-Based Elderly Population Aged 70 Years and Over
Niu, K., Hozawa, A., Guo, H., Kuriyama, S., Ebihara, S., Yang, G., Ohmori‐Matsuda, K., Nakaya, N., Takahashi, H., Fujita, K., et al. (2008) · Gerontology · doi:10.1159/000134286 · Cited by 14
The Interplay between Structural Inequality, Allostatic Load, Inflammation, and Cancer in Black Americans: A Narrative Review
Esdaille, A., Kuete, N., Anyaeche, V. I., Kalemoglu, E., & Kucuk, O. (2024) · Cancers · doi:10.3390/cancers16173023 · Cited by 13
“…Cardiovascular Health Study [76], the Men’s Health Professionals Follow-up Study, the Nurses’ Health Study II [77], the MacArthur Studies of Aging [78], the Multi-Ethnic Study of Atherosclerosis (MESA) [79], the CHIANTI study [80], and the Health, Aging, and Body Composition Study (Health ABC)…”
BackgroundMethod
Association between dietary inflammatory potential and the probable sarcopenia among community-dwelling older adults: a cross-sectional study
Esmaeily, Z., Daei, S., Rezaei, M., Eyvazkhani, A., Tajary, Z., Dara, M. M., & Motlagh, A. D. (2022) · BMC Geriatrics · doi:10.1186/s12877-022-03525-2 · Cited by 13
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Inflammatory Markers in Pediatric Obesity
Stolzman, S. C., & Bement, M. H. (2012) · ICAN Infant Child & Adolescent Nutrition · doi:10.1177/1941406412459344 · Cited by 13
Predictors of improvements in exercise capacity during cardiac rehabilitation in the recovery phase after coronary artery bypass graft surgery versus acute myocardial infarction
Suzuki, Y., Ito, K., Yamamoto, K., Fukui, N., Yanagi, H., Kitagaki, K., Konishi, H., Arakawa, T., Nakanishi, M., & Goto, Y. (2017) · Heart and Vessels · doi:10.1007/s00380-017-1076-2 · Cited by 13
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The Effect of a Community-Based, Primary Health Care Exercise Program on Inflammatory Biomarkers and Hormone Levels
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Low Socioeconomic Status and Body Mass Index as Risk Factors for Inflammation in Older Adults: Conjoint Influence on C-Reactive Protein?
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Consumption of protein-enriched milk has minor effects on inflammation in older adults—A 12-week double-blind randomized controlled trial
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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)
ORCID: Taaffe, D. R.
Harris, T. B.
Ferrucci, L.
Rowe, J.
Seeman, T. E.
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
DOI: 10.1093/gerona/55.12.m709
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 (medical) › Nutrition and Health in Aging
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Physiology (medical) › 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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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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