Red blood cells (RBCs), also known as erythrocytes, are the most abundant type of blood cell in the human body. RBCs contain hemoglobin, an iron-containing protein that carries oxygen from the lungs to tissues throughout the body. The number of RBCs in the blood is often measured as part of a complete blood count (CBC) test. This measurement, known as the RBC count, indicates the total number of red blood cells per volume of blood.
RBC production, known as erythropoiesis, occurs in the bone marrow and is stimulated by the hormone erythropoietin. New RBCs are constantly being produced to replace old or damaged RBCs that are removed from circulation. RBC production varies based on the body’s needs and is tightly regulated to maintain appropriate RBC counts in the blood.
While RBC counts are quite stable in healthy individuals, many factors can cause variations in RBC counts, including age. This article will examine how RBC counts change across the lifespan and explore the mechanisms behind age-related changes in erythropoiesis and RBC homeostasis.
RBC Counts in Newborns and Infants
At birth, newborns typically have elevated RBC counts compared to older children and adults. The normal RBC reference range for newborns is 4.5 to 7.0 million cells per microliter.[1] This neonatal polycythemia is a normal physiological response to the relatively hypoxic environment in the fetus. Higher RBC counts increase the oxygen-carrying capacity of the blood to better meet metabolic demands after birth.
Shortly after birth, the infant’s RBC count decreases dramatically over the first 2 months of life.[2] This decline is largely due to the breakdown of fetal hemoglobin and associated RBCs combined with increased blood volume as the newborn grows. By 2 to 3 months of age, the RBC reference range is 3.2 to 5.0 million cells per microliter, similar to normal counts in older children.[3]
Infants have higher daily erythropoietic activity and RBC production rates compared to adults.[4] This heightened erythropoiesis during infancy generates sufficient RBCs to accommodate the rapid growth occurring during this period.
RBC Counts in Children and Adolescents
RBC counts in children and adolescents remain relatively stable until puberty. The normal RBC reference ranges are[5]:
- 1-5 years: 3.9-5.3 million cells per microliter
- 6-11 years: 4.0-5.2 million cells per microliter
- 12-17 years girls: 4.0-5.0 million cells per microliter
- 12-17 years boys: 4.5-5.3 million cells per microliter
During puberty, androgen hormones cause a slight increase in RBC production in boys compared to girls. As a result, the average RBC count is slightly higher in adolescent males. However, RBC counts in both genders remain within normal ranges during this period of development.
RBC Counts in Young and Middle-Aged Adults
RBC production reaches its peak by early adulthood. RBC counts are generally highest between the ages of 20 and 50 years. The normal reference range for RBC count in adults is:[6]
- Men: 4.5 to 5.9 million cells per microliter
- Women: 4.0 to 5.1 million cells per microliter
The gender difference in RBC counts reflects the stimulating effects of androgens on erythropoiesis. Estrogen has the opposite effect, partially suppressing RBC production. As a result, adult women tend to have lower RBC counts compared to men of the same age.
Assuming no underlying hematological conditions, RBC counts remain relatively stable during the young and middle adult years. However, around age 50, RBC production slowly begins to decline with advancing age.
RBC Counts in Older Adults
After age 50, both men and women experience a gradual decline in RBC counts as part of the normal aging process. The rate of decrease accelerates significantly after age 70.[7] By age 80, average RBC counts are 10-15% lower compared to younger individuals.[8]
The age-related reduction in RBC counts is multifactorial:
- Diminished bone marrow erythropoietic capacity – The bone marrow contains less regenerative stem cell reserves with advanced age.[9] This contributes to reduced production of RBC precursor cells.
- Increased RBC destruction – Older RBCs are more prone to destruction (hemolysis) due to oxidative damage and reduced cell deformability.[10] The disproportionate loss of older RBCs exceeds the reduced bone marrow production capacity.
- Blunted erythropoietin response – The aged kidney produces less erythropoietin in response to falling RBC counts.[11] Impaired erythropoietin release fails to appropriately stimulate RBC production.
- Nutritional deficiencies – Deficiencies in key nutrients required for RBC production like iron, vitamin B12 and folate are more prevalent in the elderly.[12]
- Comorbidities – Many common age-related diseases such as renal failure, inflammation and malignancies can suppress erythropoiesis.[13]
The combination of these age-related changes results in a 10-20% decline in RBC counts between the ages of 30 and 80 years old.[14] Although RBC counts fall with age, they generally remain within the normal reference ranges. However, anemia is more prevalent in older populations and warrants diagnostic workup.
Normal RBC Count Ranges by Age
The following table summarizes the normal RBC count reference ranges from birth through older adulthood:[15]
| Age | Normal RBC Count Range (million cells/microliter) |
|---|---|
| Newborn | 4.5 – 7.0 |
| 2-6 months | 3.2 – 5.0 |
| 1-5 years | 3.9 – 5.3 |
| 6-11 years | 4.0 – 5.2 |
| 12-17 years (female) | 4.0 – 5.0 |
| 12-17 years (male) | 4.5 – 5.3 |
| Adult (female) | 4.0 – 5.1 |
| Adult (male) | 4.5 – 5.9 |
| >80 years | 3.2 – 4.8 |
When are age-related RBC count changes abnormal?
While RBC counts demonstrate an age-dependent decline across the lifespan, significant deviations below the expected normal ranges may indicate an underlying disorder.
In children and younger adults, persistently low RBC counts could reflect:
- Nutritional deficiencies – Iron, vitamin B12, folate
- Hemoglobinopathies – Thalassemias, sickle cell disease
- Bone marrow disorders – Leukemia, myelodysplastic syndrome, aplastic anemia
- Hereditary RBC abnormalities – Enzyme deficiencies like G6PD and PK deficiency
- Excess RBC destruction – Autoimmune hemolytic anemia
- Kidney disease – Decreased erythropoietin production
- Endocrine disorders – Hypothyroidism, hypopituitarism
In older adults, an accelerated age-related decline in RBC count may indicate:
- Myelodysplastic syndrome – Premalignant blood disorder
- Plasma cell disorders – Multiple myeloma, Waldenstrom macroglobulinemia
- Leukemia – Particularly chronic lymphocytic leukemia
- Anemia of chronic disease
- Advanced kidney disease
- Nutritional deficiencies – Vitamin B12, folate, iron
Any unexpected reductions in RBC count below the normal range for a patient’s age warrant medical evaluation to identify potential underlying causes. Monitoring longitudinal trends in RBC count over time can also provide insight into disease progression or response to treatment.
Does the RBC size change with age?
In addition to RBC counts, the average size of RBCs, measured as mean corpuscular volume (MCV), also changes across the lifespan.
At birth, newborns have a high MCV of 100-120 femtoliters.[16] These larger neonatal RBCs facilitate oxygen transfer across the placenta.
During the first months of life, the MCV declines to reach the normal childhood range of 70-84 femtoliters.[17] Children and younger adults maintain this stable MCV throughout early life.
However, in later decades, the MCV increases again. By age 80, the average MCV is 90-98 femtoliters.[18] This age-related macrocytosis reflects reduced bone marrow regenerative capacity, altered erythropoietin dynamics, and increased nutritional deficiencies in the elderly.
Conclusion
In summary, RBC counts demonstrate dynamic changes across the human lifespan. Counts are elevated at birth, reach maximal levels during young adulthood, and then slowly decline with advancing age. While the age-related reduction in RBC count is considered normal physiology, significant deviations below expected values can indicate underlying hematological or systemic disease. Monitoring RBC counts and relevant indices like MCV can provide key insights into hematopoietic function during both health and disease states.