Circulating α-Klotho Is Positively Associated with Eosinophil Counts in Community-Dwelling Older Adults: A Cross-Sectional Study

Background: Circulating α-Klotho is a longevity-related protein with anti-inflammatory and cytoprotective functions. Evidence on its relationship with individual leukocyte populations is limited, while eosinophils may have both inflammatory and tissue-homeostatic roles. We examined the association of serum α-Klotho with absolute and relative eosinophil measures in older adults. Methods: This cross-sectional analysis included 502 community-dwelling adults aged ≥60 years with serum α-Klotho data; 493 also had a complete blood count with differential. α-Klotho was analyzed continuously because no universally accepted clinical reference interval or diagnostic cut-point exists. The primary analysis assessed the Spearman correlation between α-Klotho and absolute eosinophil count; eosinophil percentage and the eosinophil-to-lymphocyte ratio were supportive measures. Robust linear regression estimated the percentage difference in α-Klotho per 1-standard-deviation increase in log-eosinophil count after adjustment for demographic, renal, hematological, smoking, and respiratory factors. Results: The median serum α-Klotho concentration was 1354.99 pg/mL (interquartile range 979.54-4047.59), and the median absolute eosinophil count was 0.14 ×10⁹/L (0.09-0.20). α-Klotho correlated positively with absolute eosinophils (Spearman ρ = 0.175; false-discovery-rate-adjusted q = 0.001), eosinophil percentage (ρ = 0.152; q = 0.004), and the eosinophil-to-lymphocyte ratio (ρ = 0.139; q = 0.008). In the fully adjusted model (n = 479), each 1-standard-deviation increase in log-eosinophils was associated with 22.3% higher α-Klotho (95% confidence interval 9.1-37.0%; p < 0.001). The association persisted after restricting α-Klotho to its 1st-99th percentiles (16.9% higher; 95% confidence interval 4.6-30.7%; p = 0.006) and after adjustment for study centre. Conclusion: Higher circulating α-Klotho was independently associated with higher absolute and relative eosinophil measures in this older Central Asian cohort. The direction differs from some population-based reports and should be considered hypothesis-generating. Prospective studies with eosinophil phenotyping, allergy and parasite assessment, and standardized α-Klotho assays are needed before the finding can be interpreted in relation to healthy longevity.