Eligible elderly men and women with anemia will undergo a full hematologic evaluation plus additional laboratory tests to determine the etiology of the anemia. In a subset of subjects, bone marrow aspirate and biopsies will be obtained for a planned analysis of erythroid progenitor and stem cells. Plasma; serum; and bone marrow samples will be will be compared to elderly non-anemic controls. Bone marrow samples will also be compared to non-anemic young controls (purchased).

Eligible elderly men and women with anemia will undergo a full hematologic evaluation (blood sample for complete blood count, CBC) to determine the etiology of the anemia (eg, myelodysplastic syndrome). Peripheral smears; iron studies; serum creatinine; serum erythropoietin; reticulocyte count; vitamin B12; and folate levels may be obtained/conducted. When no etiology is identified (ie, "unexplained anemia"), additional laboratory tests will be performed which will include some or all of urinary hepcidin levels; plasma cytokine levels; serum soluble transferrin receptor; C-reactive protein; erythrocyte sedimentation rate; D-Dimer; neopterin level; tryptophan level; and blood for a cytokine profile that may include IL-1, IL-6, TNF-alpha, and VEGF levels. Serum; plasma; and nucleated peripheral blood cells may be banked for future DNA and other analyses. In a subset of those found to have either unexplained anemia (approximately 6 to 30 subjects) or anemia of chronic inflammation (approximately 6 to 30 subjects) , bone marrow aspirate and biopsies may be performed for a planned analysis of erythroid progenitor and stem cells in these populations. In addition, plasma and serum and bone marrow samples will be obtained from elderly non-anemic controls (approximately 6 to 30 subjects), and bone marrow samples will be purchased for non-anemic young controls (approximately 6 to 30 subjects) .

INCLUSION CRITERIA: Anemic elderly :

• Age 65 or older
• Hemoglobin < 13 g/dL (men) or < 12 g/dL (women) on at least 2 occasions 30 days apart, with the most recent value within at least 14 days of enrollment into the study. In addition, if a CBC is drawn on the date of enrollment, hemoglobin must meet eligibility criteria in order for the patient to enroll.
• Outpatient at either the Stanford Health Care (SHC) Medical Center or VA Palo Alto Health Care System
• Independent/community living
• Ability to understand and the willingness to sign a written informed consent document
• Performance level ECOG 2 or better.

INCLUSION CRITERIA: Non-anemic elderly control, for blood and urine samples, with or without bone marrow biopsy

• Age 65 or older
• Hemoglobin ≥ 13 g/dL (men) or ≥ 12 g/dL (women) within at least 90 days of enrollment into the study
• Normal white blood cell and platelet counts
• Independent / community living
• Ability to understand and the willingness to sign a written informed consent document
• Performance level ECOG 2 or better
• Matched to UA population by gender and 10-year age strata (65 to < 75; 75 to < 85; 85 or older).

INCLUSION CRITERIA: Non-anemic adult control (non-elderly), for blood and urine samples, with bone marrow biopsy

• Age 20 to 35
• Hemoglobin ≥ 13 g/dL (men) or ≥ 12 g/dL (women) within at least 90 days of enrollment into the study
• Normal white blood cell and platelet counts
• Independent / community living
• Written informed consent obtained
• Performance level ECOG 2 or better

Inclusion Criteria: Non-anemic adult control (non-elderly), for blood and urine samples only

• Age 20 to 64
• Hemoglobin ≥ 13 g/dL (men) or ≥ 12 g/dL (women) within at least 90 days of enrollment into the study
• Normal white blood cell and platelet counts
• Independent / community living
• Written informed consent obtained
• Performance level ECOG 2 or better
• Will be recruited by the following age strata: 20 to < 35; 35 to < 50; 50 to < 65.

INCLUSION CRITERIA: Non-anemic adult control (non-elderly), with bone marrow biopsy

• Age 20 to 35
• Hemoglobin ≥ 13 g/dL (men) or ≥ 12 g/dL (women)

EXCLUSION CRITERIA: For all groups

• Substance abuse or mental health or other problems that would make compliance with the protocol unlikely

• Predicted mortality in less than 3 months, based on co-morbidities

• Known diagnosis of bone marrow disorder such as

  • Leukemia
  • Metastatic malignancy with bone marrow involvement
  • Myelodysplastic syndrome
  • Monoclonal gammopathy of undetermined significance (MGUS)

• On any erythropoiesis-stimulating agent in the prior 3 months

• Having received any red blood cell transfusion in the prior 3 months

• End stage renal disease as defined by the need for ongoing hemo or peritoneal dialysis

• Endstage liver disease as defined by the patient¡-s providers in the medical record

• A medical condition which would make participation risky

• On any other study requiring ongoing blood or marrow donation which would make additional blood or marrow collection risky to the subject

EXCLUSION CRITERIA: Additional, for healthy controls:

• History of active malignancy (except non-melanoma skin cancer), or radiation or chemotherapy for treatment of malignancy within the past 24 months
• HIV positivity
• Hepatitis B or Hepatitis C positivity
• Autoimmune disease (including lupus, RA, IBD)
• Known hematologic disorder

Outpatient elderly men and women (aged 65 years or older) with anemia, and corresponding elderly controls and adult non-elderly controls.