In the subgroup analyses, significant negative associations between caffeine consumption and Klotho concentrations were observed among participants aged ≥58 years (p = 0.009), with higher education (college or above, p = 0.005), high income (p < 0.001), serum cotinine <1 ng/mL (p < 0.001), normal kidney function (eGFR ≥90 mL/min/1.73 m2, p = 0.021), sedentary activity >480 min daily (p = 0.001), and without diabetes (p = 0.018), hypertension (p = 0.001), CHD (p = 0.014), or cancer (p = 0.004). The gene discussed is KL; the disease is cancer.