Elevated Serum Carboxymethyl-Lysine, an Advanced Glycation End Product, Predicts Severe Walking Disability in Older Women: The Women's Health and Aging Study I

Advanced glycation end products (AGEs) have been implicated in the pathogenesis of sarcopenia. Our aim was to characterize the relationship between serum carboxymethyl-lysine (CML), a major circulating AGE, and incident severe walking disability (inability to walk or walking speed < 0 . 4 ？m/sec) over 30 months of followup in 394 moderately to severely disabled women, ≥ 6 5 years, living in the community in Baltimore, Maryland (the Women’s Health and Aging Study I). During followup, 154 (26.4%) women developed severe walking disability, and 23 women died. Women in the highest quartile of serum CML had increased risk of developing of severe walking disability in a multivariate Cox proportional hazards model, adjusting for age and other potential confounders. Women with elevated serum CML are at an increased risk of developing severe walking disability. AGEs are a potentially modifiable risk factor. Further work is needed to establish a causal relationship between AGEs and walking disability. 1. Introduction Mobility difficulties are common among older adults and are associated with poor quality of life [1], increased need for care, and are predictive of death [2–4]. Understanding the processes that lead to disability is important in order to develop strategies to prevent or delay disability in older adults. Lifestyle factors that may influence the pathway to disability include diet. Diet has been incompletely characterized in relation to the development of disability. Recent studies suggest that advanced glycation end products (AGEs), which are active biomolecules formed by the non-enzymatic covalent binding of sugars with proteins and other molecules, may be related to muscle strength and physical performance [5, 6]. The western diet is high in AGEs, which are formed in high concentrations in foods that are prepared at high temperatures. Thus, some foods are considered an important exogenous source of AGEs. AGEs are thought to be absorbed in the process of digestion, circulate in the blood, and can be deposited in different organs and tissues [7]. Sarcopenia, or loss of muscle strength and muscle mass, is an important factor underlying mobility difficulties such as slow walking speed in older adults [8]. Older adults have increased cross-linking of collagen and deposition of AGEs in skeletal muscle [9]. In aging animals, cross-linking of collagen is associated with increased muscle stiffness, reduced muscle function [10, 11], and accumulation of AGEs [12]. AGEs may also play a role in sarcopenia through upregulation of inflammation and endothelial