Frequent cannabis use was linked to lower levels of Klotho, a protein associated with healthy aging, in middle-aged adults

Frequent cannabis users had significantly lower Klotho levels than never users (adjusted estimate = -57.94, p = 0.027), with a significant dose-dependent trend (p = 0.022). The association persisted in non-smokers (p = 0.047), confirming a cannabis-specific effect. Amplified reductions appeared in those with prolonged sedentary behavior (>240 min/day), higher vitamin D, and cancer.

Cross-sectional analysis of 5,827 adults aged 40-59 from NHANES 2007-2016. Cannabis use was self-reported via computer-assisted interviews. Serum Klotho was measured by ELISA. Weighted multivariable generalized linear models with subgroup analyses, interaction tests, and E-value sensitivity analysis were used.

Klotho is increasingly recognized as a key biomarker of biological aging, with lower levels linked to cardiovascular disease, cognitive decline, and metabolic dysfunction. If frequent cannabis use reduces Klotho, it could accelerate aging-related health problems.

This connects cannabis use to a biological aging marker for the first time using nationally representative data. The finding that the effect was stronger in metabolically healthier subgroups is counterintuitive and warrants further investigation.

Cross-sectional design cannot establish causation. Self-reported cannabis use may be inaccurate. Klotho was measured at a single time point. Cannot determine if lower Klotho preceded or followed cannabis use. The 3.13% population attributable fraction is small.