Age-Associated Changes in Mean Corpuscular Volume and Leukocyte Ratios in U.S. Adults

Background: The associations between mean corpuscular volume (MCV) and leukocyte-derived ratios and chronological aging remain poorly understood. We aimed to evaluate the association between MCV and leukocyte-derived ratios and chronological age in U.S. adults. Methods: This cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES, n = 9259) and the Health and Aging Brain Study–Health Disparities (HABS-HD, n = 770). Participants were aged ≥20 years, and individuals with hemoglobin levels outside 12–18 g/dL or C-reactive protein (CRP) > 1 mg/dL were excluded. Associations between age and MCV, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), neutrophil-to-monocyte ratio (NMR), and platelet-to-white blood cell ratio (PWR) were examined using quartile comparisons and multivariable linear regression adjusted for sex, race/ethnicity, CRP, and red cell folate and hemoglobin. Results: In both cohorts, higher quartiles of MCV, NLR, and MLR were associated with older mean age. In adjusted marker-specific models, MCV, NLR, and MLR were each positively associated with chronological age. In composite models, MCV remained independently associated with older age in both NHANES (β = 0.646, 95% CI 0.567–0.725) and HABS–HD (β = 0.300, 95% CI 0.156–0.445). Conclusions: MCV and selected leukocyte-derived ratios are significantly associated with chronological age across two U.S. cohorts, with MCV showing the most consistent independent association.