Hepcidin and the pathogenesis of anemia in older adults.

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DESCRIPTION (provided by applicant): Anemia is common in older adults and is associated with a wide spectrum of adverse outcomes, including reduced quality of life, weakness, fatigue, disability, and increased mortality. Anemia among older adults is caused by renal failure, chronic inflammation, and nutritional deficiencies, and about one-third of the anemia is unexplained. Hepcidin, a recently discovered peptide hormone, may be a major modulator in the anemia of inflammation. Hepcidin appears to be the principal regulator of iron metabolism and is upregulated by an iron-replete state, iron overload, and inflammation. The role of hepcidin in anemia among older adults has not been well characterized. A low grade proinflammatory state is common in older adults, but it is unclear if this state can lead to the upregulation of hepcidin and contribute to anemia. We hypothesize that (i) the low grade proinflammatory state in older adults, even in the absence of clinically apparent disease, can cause anemia through the upregulation of hepcidin, (ii) unexplained anemia is characterized by high urinary hepcidin levels, and (iii) older adults with elevated urinary hepcidin levels at enrollment are at higher risk of remaining anemic or developing anemia. Our specific aims are to characterize different forms of anemia, including overlapping causes of anemia, in older adults, to study the relationship between the proinflammatory state and upregulation of hepcidin, to characterize the relationships between hemoglobin, hepcidin, nutritional status, inflammation, and hormonal status in the different forms of anemia among older adults, to identify predictors (clinical and biological markers, including hepcidin) that are associated with an increased risk of developing anemia, and to characterize longitudinal changes in hepcidin in relation to hemoglobin and inflammation. To address these aims we will measure urinary hepcidin levels in the ongoing NIH-funded InCHIANTI study, a population-based, prospective epidemiological study of aging conducted among 1453 men and women in the Chianti area (Tuscany) of Italy. The subjects were originally recruited in 1998-2000 and are seen every three years until 2007-2009. The study includes a rich database related to inflammation, anemia, nutrition, hormones, and physical performance, chronic disease, disability, and mortality. This study should provide new insight into the epidemiology and biological mechanisms of anemia among older adults and help identify strategies aimed at the prevention and treatment of anemia.