Background: The relation of circulating α-Klotho to individual leukocyte populations is uncertain. An exploratory 13-marker hematological screen identified eosinophils as a candidate signal, motivating this focused analysis. Methods: The grant-funded α-Klotho substudy included 504 assayed serum specimens. After excluding one participant aged < 60 years and one with missing age, 502 participants were eligible. α-Klotho was measured with the FineTest Human SAKL ELISA kit (EH4278; calibration range 93.75–6000 pg/mL). Because results above the upper calibrator had been software-extrapolated without repeat dilution, the primary analysis was restricted to 397 participants with reported concentrations ≤ 6000 pg/mL; 388 had an eosinophil count. Spearman’s correlations were corrected across 13 hematological markers using Benjamini–Hochberg adjustment. Ordinary least-squares models used HC3 heteroskedasticity-consistent standard errors. Results: Median α-Klotho in the primary cohort was 1179.67 pg/mL (IQR 920.07–1686.51). Absolute eosinophil count correlated weakly with α-Klotho (ρ = 0.120; p = 0.018), but the association did not survive correction across the screening family (q = 0.146). In the fully adjusted model (n = 376), each 1 SD higher log-eosinophil count was associated with 8.4% higher α-Klotho (95% CI 2.0–15.2%; p = 0.009). The quartile trend was significant (p = 0.019), whereas median regression produced a smaller estimate (5.4%; bootstrap 95% CI −0.6 to 12.5%). Estimates were similar after recruitment-stratum adjustment and after excluding eosinophilia, chronic respiratory disease, or leukocyte counts > 15 × 10⁹/L. Conclusions: Within the assay calibration range, higher eosinophil counts were associated with modestly higher serum α-Klotho after adjustment for measured covariates. The post hoc origin, assay limitations, and cross-sectional design make this a hypothesis-generating immune association rather than evidence of causality, healthy longevity, or a clinical threshold.

Introduction: Global aging and the growing burden of age-related disease have intensified interest in modifiable biomarkers of biological age. α -Klotho, the product of the KL gene, is a pleiotropic anti-aging protein whose circulating (soluble, s-Klotho) form declines with age and is independently associated with all-cause mortality, sarcopenia, cognitive deficit, and cardiovascular events. We conducted a systematic review and meta-analysis of publications from 2015 to 2025 evaluating the effect of exercise training [aerobic, resistance, high-intensity interval training (HIIT), combined] on circulating α-Klotho in adults, with emphasis on individuals aged ≥60 years and patients with chronic kidney disease (CKD), diabetes, and sarcopenia. Methods: A systematic search of PubMed, Scopus, Web of Science, Cochrane CENTRAL, EMBASE, PEDro, and CINAHL (inception–April 2025) identified randomized and quasi–randomized controlled trials (RCTs) reporting serum or plasma α–Klotho measured by enzyme–linked immunosorbent assay (ELISA). A random–effects model (Hartung–Knapp–Sidik–Jonkman correction) was used; effect size was expressed as Hedges' g or mean difference (MD) with 95% confidence intervals (CI), and heterogeneity was assessed by I2. Results: Fourteen RCTs ( n = 893; age range 30–94 years) were included. The pooled effect of chronic training (≥12 weeks) on s-Klotho was Hedges' g = 1.20 (95% CI 0.85–1.55; P < 0.0001; I2 = 84%). In patients with CKD, exercise significantly increased Klotho (MD = 158.82 pg/mL; 95% CI 122.33-194.31; I2 = 0%; P = 0.001) and reduced fibroblast growth factor 23 (FGF23) (MD = −102.07 pg/mL; 95% CI −176.23 to −27.91; I2 = 97%; P = 0.001). Resistance training and HIIT showed the most robust modality-specific effects, whereas combined aerobic-resistance programs were the least reproducible. In pre-frail older adults ( n = 69, mean age 77 years), 12-week classical resistance, but not power training, significantly increased s-Klotho. Conclusion: Regular exercise, particularly resistance training and HIIT, can be considered a consistent stimulus for increasing circulating α -Klotho across diverse adult populations. Circulating s-Klotho is best regarded as a promising biomarker of the biological response to exercise rather than a validated therapeutic target; the 700–1,000 pg/mL range in adults aged ≥60 years is presented only as an observational reference pending prospective validation. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=1415238 , PROSPERO identifier CRD420261415238.

Introduction. Older adults are vulnerable to insufficient micronutrient intake, altered nutrient metabolism, and cardiometabolic risk. Dietary assessment estimates nutrient exposure, whereas serum biomarkers integrate intake with absorption, distribution, metabolism, chronic disease, and supplement use. Dietary antioxidant scores and serum micronutrient profiles may therefore provide different classifications for the same individuals. Evidence on concordance between these approaches in older adults remains limited. Objective. To evaluate concordance between an energy-adjusted dietary antioxidant index and a serum antioxidant micronutrient index in older adults, identify clinical and behavioral factors associated with the serum index, and examine its relationships with biochemical indicators and risk categories derived from A Body Shape Index. Methods. This cross-sectional study included 215 older adults with demographic, anthropometric, dietary, and laboratory data. Dietary intake was assessed by a twenty-four-hour dietary recall. The energy-adjusted dietary antioxidant index combined standardized residual intakes of vitamins A, C, D, and E and selenium. The serum antioxidant micronutrient index combined standardized concentrations of the same five components; serum vitamin E was adjusted for total cholesterol. Concordance was evaluated using Spearman correlation, a bootstrap confidence interval based on 2000 resamples, tertile agreement, and quadratically weighted Cohen kappa. The Benjamini–Hochberg procedure was applied to component-level comparisons. Factors associated with the serum index were examined using linear regression with robust standard errors. Associations with A Body Shape Index categories were evaluated using nonparametric tests and logistic regression adjusted for age and sex. Results. The median age was 68 years, and 165 participants were women. The dietary index was available for 207 participants and the serum index for all 215 participants. Correlation between the indices was weak and did not reach statistical significance (Spearman correlation coefficient 0.128; 95 percent bootstrap confidence interval from -0.007 to 0.263; p=0.066). Exact tertile agreement was 39.1 percent, and quadratically weighted Cohen kappa was 0.152. After adjustment for multiple comparisons, vitamin D was the only component with a significant association between dietary intake and serum concentration. Use of vitamin or mineral supplements was independently associated with a higher serum index (standardized regression coefficient 0.512; p<0.001). The serum index differed across A Body Shape Index risk categories. Each one-standard-deviation increase in the serum index was associated with lower odds of increased risk after adjustment for age and sex (odds ratio 0.43; 95 percent confidence interval from 0.24 to 0.78; p=0.005). Conclusion. Dietary antioxidant potential and serum antioxidant micronutrient status showed low concordance and should not be interpreted as interchangeable measures. Supplement use, particularly vitamin D supplementation, was more strongly related to circulating status than the dietary index. Combined but separate interpretation of dietary and laboratory assessments may improve personalized nutritional evaluation in older adults. Keywords: aged, antioxidants, micronutrients, nutritional status, biomarkers, anthropometry.

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.