Klotho levels and biological age acceleration: Insights from a diverse cohort of middle-aged and elderly individuals.

Abstract

Aging is characterized by progressive physiological and psychological changes, leading to decreased cellular metabolism and increased vulnerability to age-related diseases. In this study, we examined the relationship between circulating Klotho levels and biological age acceleration (BAA) in a representative cohort of middle-aged and older adults. Data were obtained from the National Health and Nutrition Examination Survey (NHANES, 2007-2010), including 5,654 participants aged 45-85 years. Serum Klotho concentrations were quantified using ELISA, while biological age was estimated with the BioAge R package. Linear regression analyses demonstrated a robust inverse association between log-transformed Klotho levels and BAA across all statistical models, with reductions of -1.06 (95% CI: -1.77 to -0.36, p = 0.005), -1.44 (95% CI: -2.15 to -0.73, p < 0.001), and -1.30 (95% CI: -2.20 to -0.40, p = 0.01). Consistent results were observed in logistic regression models, where higher Klotho concentrations were linked to lower odds of accelerated aging (OR = 0.72, 95% CI: 0.59-0.88, p = 0.002; OR = 0.63, 95% CI: 0.51-0.77, p < 0.0001; OR = 0.62, 95% CI: 0.46-0.84, p = 0.01). Subgroup analyses revealed significant associations in women, participants over 60 years of age, and individuals without chronic illnesses. Interaction analyses further indicated that age (p-interaction = 0.002), alcohol intake (p-interaction = 0.04), and diabetes status (p-interaction = 0.03) significantly modified the Klotho-BAA relationship. Moreover, restricted cubic spline analysis showed a non-linear L-shaped dose-response pattern, suggesting that the protective effect of Klotho becomes more pronounced above a certain threshold. Collectively, these findings underscore the pivotal role of Klotho in the biology of aging and emphasize the importance of accounting for demographic and health-related modifiers in future investigations.