Research Blog
Welcome to part 8 of ODX's "Biological Age Biomarkers" Series. In the eighth post, you'll learn about MCV's role in cognitive decline and why MCV values outside of optimal are associated with various age-related disorders.
The ODX Biological Age Biomarkers Series
Dicken Weatherby, N.D. and Beth Ellen DiLuglio, MS, RDN, LDN
- Biological Age Biomarkers Part 1: Introduction and Overview
- Biological Age Biomarkers Part 2: Fasting Glucose
- Biological Age BioMarkers Part 3: C-Reactive Protein (CRP)
- Biological Age Biomarkers Part 4: Albumin
- Biological Age BioMarkers Part 5: Alkaline Phosphatase
- Biological Age BioMarkers Part 6: Creatinine
- Biological Age BioMarkers Part 7: Red Cell Distribution Width (RDW)
- Biological Age BioMarkers Part 8: Mean corpuscular volume (MCV)
- Biological Age BioMarkers Part 9: Lymphocytes
- Biological Age BioMarkers Part 10: WBCs
Mean corpuscular volume (MCV) reflects hematological function
Physiological changes associated with elevated MCV
The mean corpuscular volume reflects the average size or volume of a red blood cell and is a part of the RDW calculation. A decreased MCV indicates small “microcytic” RBCs which occur with iron-deficiency anemia, sideroblastic anemia, or thalassemia. A decreased MCV may occur in association with blood loss, lead poisoning, malabsorption, malignancy, and iron, copper, or vitamin B6 deficiency (Cappellini 2015, Maner 2021).
An elevated MCV indicates the RBC is larger than normal and is considered macrocytic, a condition most often associated with folate or B12 deficiency (Maner 2021), which impairs DNA synthesis, causing megaloblastic anemia. Non-megaloblastic anemia may be due to genetic factors, hepatic insufficiency, or alcohol abuse (Lee 2022).
Measurement of MCV is useful in determining the underlying cause of anemia, defined as a hemoglobin below 13 g/dL in males and below 12 g/dL in females. However, MCV may be elevated irrespective of hemoglobin in cases of alcoholism, liver disease, malignancy, chemotherapy, chronic kidney disease, ischemic stroke, and cardiac interventions (Lee 2022)
The increase in MCV is observed with aging may be partly due to a shorter RBC lifespan leading to a compensatory increase in RBCs and increased circulation of younger RBCs that tend to have a higher MCV (Gamaldo 2011). Larger RBCs may have difficulty passing through capillaries, impairing the delivery of oxygen and nutrients. Additional age-related factors that may contribute to a higher MCV include oxidative stress, inflammation, and folate or vitamin B12 insufficiency (Gamaldo 2013).
MCV and cognitive decline
Changes in MCV and in cognitive performance are observed with aging. Analysis of Baltimore Longitudinal Study of Aging data found that a higher MCV significantly correlated with worsening performance on standardized cognitive testing, including attention, global mental status, and verbal long delay memory performance. Circulatory impairment can magnify these deficit. The rate of cognitive decline was accelerated with an MCV of 97 or above. The association of poor cognitive performance and higher MCV was independent of the presence of anemia or inflammation (Gamaldo 2013).
MCV and biological age
Mean corpuscular volume values outside of optimal are associated with various age-related disorders including Alzheimer's, Parkinson’s, and macular degeneration, with an increase in MCV correlating with aging itself. In vivo hematopoietic stem cell research has indicated that cell enlargement is causally related to aging (Davies 2022).
Elevated MCV is considered a risk factor for morbidity and mortality in certain clinical presentations. An MCV above 95 fL was associated with arterial stiffening in young healthy subjects. A higher MCV was associated with endothelial dysfunction, insulin resistance, and all-cause, CVD, and infection-associated mortality in chronic kidney disease patients. Elevated MCV is also associated with cognitive decline. The link between higher MCV and aging has not been clearly defined, though researchers note a definitive increase after age 25, possibly linked to accelerated aging following the reproductive years (Lee 2022).
A mean MCV of 91 fL was associated with mortality in critical care myocardial infarction patients, whereas a mean MCV of 89 fL was associated with survival in a review of ICU hospital records (Huang 2016).
References
Cappellini, M Domenica, and Irene Motta. “Anemia in Clinical Practice-Definition and Classification: Does Hemoglobin Change With Aging?.” Seminars in hematology vol. 52,4 (2015): 261-9. doi:10.1053/j.seminhematol.2015.07.006
Davies, Daniel M et al. “Cellular enlargement - A new hallmark of aging?.” Frontiers in cell and developmental biology vol. 10 1036602. 10 Nov. 2022, doi:10.3389/fcell.2022.1036602
Gamaldo, Alyssa A et al. “Age-related changes in mean corpuscular volume in adult whites and African Americans.” Journal of the American Geriatrics Society vol. 59,9 (2011): 1763-4. doi:10.1111/j.1532-5415.2011.03583.x
Gamaldo, Alyssa A et al. “Relationship between mean corpuscular volume and cognitive performance in older adults.” Journal of the American Geriatrics Society vol. 61,1 (2013): 84-9. doi:10.1111/jgs.12066
Huang, Yuan-Lan, and Zhi-De Hu. “Lower mean corpuscular hemoglobin concentration is associated with poorer outcomes in intensive care unit admitted patients with acute myocardial infarction.” Annals of translational medicine vol. 4,10 (2016): 190. doi:10.21037/atm.2016.03.42
Lee, Jin Young et al. “Age-related changes in mean corpuscular volumes in patients without anaemia: An analysis of large-volume data from a single institute.” Journal of cellular and molecular medicine vol. 26,12 (2022): 3548-3556. doi:10.1111/jcmm.17397
Maner, Brittany S. and Leila Moosavi. “Mean Corpuscular Volume.” StatPearls, StatPearls Publishing, 10 July 2021.
Nagao, Takayo, and Makoto Hirokawa. “Diagnosis and treatment of macrocytic anemias in adults.” Journal of general and family medicine vol. 18,5 200-204. 13 Apr. 2017, doi:10.1002/jgf2.31
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