Biomarkers of oxidative stress are associated with frailty: the Framingham Offspring Study
Open accessAbstract
Cardiovascular disease and frailty frequently occur together. Both are associated with inflammation, which may be partially triggered by oxidative stress, especially in cardiovascular disease. We investigated whether inflammatory and oxidative stress biomarkers linked to cardiovascular disease were associated with frailty and the related outcome of gait speed. We report cross-sectional associations of biomarkers and frailty assessed at Framingham Offspring Study cycle eight. Participants ≥60 years were eligible if they had information on frailty and at least one of the following: C-reactive protein, interleukin-6, tumor necrosis factor receptor 2, 8-epi-FGFα isoprostanes (isoprostanes), lipoprotein phospholipase A2 (LpPLA2) mass or activity, osteoprotegerin, intracellular adhesion molecule-1, monocyte chemoattractant protein-1 or P-selectin. Stepwise logistic models were utilized for frailty and stepwise linear models for gait speed. Covariates included age, sex, body mass index, smoking, and co-morbidities. Odds ratios (ORs) and slope estimates (B) are reported per standard deviation increase of loge-transformed biomarker. Of the 1919 participants, 142 (7 %) were frail. In a stepwise model, frailty odds increased with higher interleukin-6 (OR 1.90, 95 % CI 1.51, 2.38), isoprostanes (OR 1.46, 95 % CI 1.12, 1.92), and LpPLA2 mass (OR 1.29, 95 % CI 1.00, 1.65). Stepwise regression found that slower gait speeds were associated with interleukin-6 (B = -0.025 m/s, 95 % CI 0.04, -0.01), isoprostanes (B = -0.019, 95 % CI -0.03, -0.008), LpPLA2 mass (B = -0.016, 95 % CI -0.03, -0.004), and osteoprotegerin (B = -0.015, 95 % CI -0.03, -0.002, all p < 0.05). Interleukin-6, isoprostanes, and LpPLA2 mass were associated with greater frailty odds and slower gait speeds. Oxidative stress may be a mechanism contributing to frailty.
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The inflammatory milieu further contributes to aging-associated functional decline via reactive oxidative species-mediated exacerbation of telomere dysfunction and accelerated muscle catabolism, promoting cell senescence and subsequent disease, frailty, and mortality.
“This inflammatory milieu further contributes to aging-associated functional decline via reactive oxidative species–mediated exacerbation of telomere dysfunction34 and accelerated muscle catabolism, promoting cell senescence and subsequent disease, frailty, and mortality.33,35,36”
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- Authors
- Liu, C. K., Lyass, A., Larson, M. G., Massaro, J. M., Wang, N., D’Agostino, R. B., Benjamin, E. J., & Murabito, J. M.
- Affiliations
- Boston University (US)
- Corresponding author
- Liu, Christine K.
- Murabito, Joanne M.
- ORCID
- Venue
- AGE
- Published
- 2015-12-23
- Volume
- 38
- Issue
- 1
- Pages
- 1-1
- ISSN
- 0161-9152 (ISSN-L)
- 1574-4647
- PMC
- PMC5005887
- OpenAlex
- W2233881453
- Cited by
- 157
- References
- 56
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 19 · 2023: 11 · 2022: 30 · 2021: 13 · 2020: 18 · 2019: 15 · 2018: 13 · 2017: 15 · 2016: 11 · 2013: 1
- FWCI
- 6.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- AGE (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01-AG029451, 1R01-AG028321)
- National Heart, Lung, and Blood Institute (1R01-HL64753, R01-HL076784, N01-HC-25195)
- American Federation for Aging Research
- John A. Hartford Foundation
- U.S. Department of Agriculture (Agreement no. 1950-51000-068-01S)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Frailty in Older Adults
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Keywords
- frailty, oxidative stress, inflammatory markers, walking speed, interleukin-6, isoprostanes, osteoprotegerin, cardiovascular disease, older adults, Framingham Offspring Study, C-reactive protein, tumor necrosis factor receptor 2, P-selectin, MCP-1
- MeSH terms
- Aged, Aging, Cardiovascular Diseases, Cross-Sectional Studies, Enzyme-Linked Immunosorbent Assay, Female, Follow-Up Studies, Humans, Male, Nephelometry and Turbidimetry, Prospective Studies, Risk Factors, Time Factors, United States, Biomarkers, Body Mass Index, Incidence, Odds Ratio, Frail Elderly, Oxidative Stress
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