Higher circulating Klotho levels were robustly and inversely associated with biological age acceleration in middle-aged and older adults, with a non-linear L-shaped dose-response pattern suggesting the protective effect becomes more pronounced above a certain threshold.
Key Findings
Results
Linear regression analyses demonstrated a robust inverse association between log-transformed Klotho levels and biological age acceleration (BAA) across all statistical models.
Three models showed 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)
Data were from NHANES 2007-2010, including 5,654 participants aged 45-85 years
Serum Klotho concentrations were quantified using ELISA
Biological age was estimated with the BioAge R package
Results
Logistic regression models showed that higher Klotho concentrations were linked to lower odds of accelerated aging.
Three models yielded: OR = 0.72 (95% CI: 0.59-0.88, p = 0.002), OR = 0.63 (95% CI: 0.51-0.77, p < 0.0001), and OR = 0.62 (95% CI: 0.46-0.84, p = 0.01)
Results were described as 'consistent' with the linear regression findings
All three models showed statistically significant inverse associations
Results
Subgroup analyses revealed that the inverse association between Klotho and BAA was significant in specific demographic and health subgroups.
Significant associations were observed in women
Significant associations were found in participants over 60 years of age
Significant associations were also found in individuals without chronic illnesses
Results
Interaction analyses indicated that age, alcohol intake, and diabetes status significantly modified the Klotho-BAA relationship.
Age showed a significant interaction effect (p-interaction = 0.002)
Alcohol intake showed a significant interaction effect (p-interaction = 0.04)
Diabetes status showed a significant interaction effect (p-interaction = 0.03)
Results
Restricted cubic spline analysis revealed a non-linear L-shaped dose-response pattern between Klotho levels and BAA.
The pattern was described as 'L-shaped,' suggesting a threshold effect
The protective effect of Klotho was described as becoming 'more pronounced above a certain threshold'
This non-linear relationship was identified using restricted cubic spline analysis
Methods
The study used a representative cohort of middle-aged and older adults from NHANES spanning 2007-2010.
The cohort included 5,654 participants aged 45-85 years
The dataset was drawn from the National Health and Nutrition Examination Survey (NHANES), 2007-2010
The sample was described as a 'diverse cohort of middle-aged and elderly individuals'
Huang M, Huang G, Wu C, Zhu L, Pei B, Wang H, et al.. (2026). Klotho levels and biological age acceleration: Insights from a diverse cohort of middle-aged and elderly individuals.. PloS one. https://doi.org/10.1371/journal.pone.0343429