There are conflicting data regarding expected changes in serum erythropoietin (EPO) with advancing age, primarily because prior reports have been based upon cross-sectional analyses of diverse populations. To examine changes in serum EPO with age, we reviewed the clinical history, hematological parameters and serum EPO levels of 143 participants in the Baltimore Longitudinal Study on Aging (BLSA) who were studied at 1 – 2 year intervals for eight to thirty years. None had anemia at the time of the first visit (by WHO criteria: <12g/dL for women; or <13 g/dL for men) but it developed in 10 (7%) over the period of evaluation. An additional 20 individuals (14%) had a fall in hemoglobin of 1.5 g/dL or more, sustained over at least two visits, and for the purpose of this analysis were also considered anemic. EPO levels rose significantly with age 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 or hypertension. Subjects who developed anemia but did not have hypertension or diabetes had the greatest slope in EPO rise over time. In contrast, those who had, or developed hypertension or diabetes during the period of follow-up within the BLSA, had significantly higher initial EPO levels and a reduced EPO slope over time. The increase in serum EPO with aging may be compensating for increased RBC turnover or increased EPO resistance of red cell precursors. We suspect that with very advanced age, or in those with compromised renal function (e.g., diabetes or hypertension), the compensatory mechanism becomes inadequate.

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