Objectives: To determine the changes in serum erythropoietin with age in patients with and without anemia and to assess the importance of certain comorbidities on changes in erythropoietin level and the development of anemia.

Design: Clinical history, hematological parameters, and serum erythropoietin levels were examined at 1- to 2-year intervals for 8 to 30 years.

Setting: Baltimore Longitudinal Study on Aging (BLSA), National Institute on Aging.

Participants: One hundred forty-three BLSA participants.

Measurements: Complete blood count and serum chemistries were performed at the time of each visit, and archived serum samples were used for erythropoietin level.

Results: Although all subjects were healthy and without anemia at the time of initial evaluation, some developed chronic illness-most notably hypertension and diabetes mellitus. Erythropoietin levels rose significantly for the group as a whole, and the slope of the rise was found to be greater for those who did not have associated diabetes mellitus or hypertension. During the subsequent years, subjects who developed anemia but did not have hypertension or diabetes mellitus had the greatest slope in erythropoietin rise over time, whereas those with hypertension or diabetes mellitus and anemia had the lowest erythropoietin slope.

Conclusion: The increase in serum erythropoietin with aging may be compensation for subclinical blood loss, increased red blood cell turnover, or increased erythropoietin resistance of red cell precursors. It is suspected that, with very advanced age, or in those with compromised renal function (e.g., diabetes mellitus or hypertension), the compensatory mechanism becomes inadequate and anemia results.

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