Serum 25-Hydroxyvitamin D, Plasma Klotho, and Lower-Extremity Physical Performance Among Older Adults: Findings From the InCHIANTI Study

Abstract

Background: The hormone klotho is encoded by aging-suppressor gene klotho and has multiple roles, including regulating mineral (calcium and phosphate) homeostasis. Vitamin D also regulates mineral homeostasis and upregulates klotho expression. Klotho positively relates to longevity, upper-extremity strength, and reduced disability in older adults; however, it is unknown whether circulating klotho relates to lower-extremity physical performance or whether the relation of vitamin D with physical performance is mediated by klotho.

Methods: Klotho and 25-hydroxyvitamin D [25(OH)D] were measured in 860 participants aged ≥ 55 years in Invecchiare in Chianti, "Aging in Chianti" (InCHIANTI), a prospective cohort study comprising Italian adults. Lower-extremity physical performance was measured using the Short Physical Performance Battery, a summary score of balance, chair stand ability, and walking speed. Weighted estimating equations related plasma klotho and serum 25(OH)D concentrations measured at one visit to Short Physical Performance Battery measured longitudinally at multiple visits.

Results: Each additional natural log of klotho (pg/mL) was associated with 0.47 higher average Short Physical Performance Battery scores (95% confidence interval: 0.08 to 0.86, p value = .02) after adjustment for covariates, including 25(OH)D. Each natural log of 25(OH)D (ng/mL) was associated with 0.61 higher average Short Physical Performance Battery scores (95% confidence interval: 0.35 to 0.88, p value < .001) after adjustment for covariates, a result that changed little after adjustment for klotho.

Conclusions: Plasma klotho and 25(OH)D both positively related to lower-extremity physical performance. However, the findings did not support the hypothesis that klotho mediates the relation of 25(OH)D with physical performance.

Keywords: Biomarkers; Epidemiology; Metabolism; Physical f; Physical p; erformance.; unction.

Figure 1.

Directed acyclic graphs depicting possible pathways linking 25(OH)D, klotho, and PTH to lower-extremity physical performance. In all pathways (A–C), klotho and PTH are hypothesized mediators of 25(OH)D on lower-extremity physical performance. (A) PTH mediates the effect of klotho on lower-extremity physical performance (Model 2 and Mediation Model 1 appropriate); (B) PTH confounds the effect of klotho on lower-extremity physical performance (Model 3 and Mediation Model 2 appropriate); (C) Klotho and PTH affect lower-extremity physical performance through separate pathways (all models appropriate). 25(OH)D, 25-hydroxyvitamin D; PTH, parathyroid hormone.