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J Gerontol A Biol Sci Med Sci. 2014 Jun;69(6):710-6. doi: 10.1093/gerona/glt155. Epub 2013 Oct 14.

Serum carboxymethyl-lysine, disability, and frailty in older persons: the Cardiovascular Health Study.

Author information

1
Department of Medicine, Duke University, Durham, North Carolina. Durham VA Medical Center, GRECC, Durham, North Carolina. heather.whitson@duke.edu.
2
Department of Biostatistics, University of Washington, Seattle.
3
Department of Medicine, Harvard Medical School, Boston, Massachusetts.
4
Department of Medicine, and Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York.
5
Departments of Medicine & Prevention and Family Medicine, University of California, San Diego. Nephrology Section, Veterans Affairs San Diego Healthcare System, California.
6
Department of Medicine, University of Washington, Seattle.
7
Department of Pathology, University of Vermont, Colchester.
8
Puget Sound VA Medical Center, Seattle, Wahington. Department of Psychiatry, University of Washington, Seattle.
9
Department of Medicine, University of California Davis.
10
Department of Epidemiology, University of Pittsburgh, Pennsylvania.
11
National Institute on Aging, National Institutes of Health, Bethesda, Maryland.

Abstract

BACKGROUND:

Advanced glycation endproducts are biologically active compounds that accumulate in disordered metabolism and normal aging. Carboxymethyl-lysine (CML), a ubiquitous human advanced glycation endproduct, has been associated with age-related conditions and mortality. Our objective was to ascertain the relationship between CML and geriatric outcomes (disability and frailty) in a large cohort of older men and women.

METHODS:

In 1996-1997, serum CML was measured in 3,373 Cardiovascular Health Study participants (mean age 78.1 ± 4.8 years). Disability, defined as difficulty in any of six activities of daily living, was assessed every 6-12 months for 14 years. Frailty was defined according to five standard criteria at the 1996-1997 visit. Cox proportional hazard models estimated the relationship between CML and incident disability (N = 2,643). Logistic regression models estimated the relationship between CML and prevalent frailty.

RESULTS:

Adjusting for multiple potential confounders, higher CML was associated with incident disability (hazard ratio per standard deviation [225 ng/mL] increase: 1.05, 95% CI 1.01-1.11). In men, odds of frailty increased with higher CML values (odds ratio = 1.30 per standard deviation, 95% CI 1.14-1.48), but the relationship was attenuated by adjustment for cognitive status, kidney function, and arthritis. CML was not associated with frailty in women.

CONCLUSIONS:

Higher serum CML levels in late life are associated with incident disability and prevalent frailty. Further work is needed to understand CML's value as a risk stratifier, biomarker, or target for interventions that promote healthy aging.

KEYWORDS:

Biomarkers; Disablement process; Epidemiology; Frailty; Metabolism.

PMID:
24127427
PMCID:
PMC4022092
DOI:
10.1093/gerona/glt155
[Indexed for MEDLINE]
Free PMC Article

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