(A) Left panel: Relative serum Klotho concentrations in young WT (n = 10), aged WT (n = 7), and young heterozygous Klotho-KO (KL-KO) mice (n = 8) fed a normal-salt (NS) diet. *P < 0.05 vs. young WT. Middle and right panels: Effects of Klotho supplementation (KL) on serum Klotho in aged WT (middle panel, n = 8 each) and KL-KO mice fed a high-salt (HS) diet (right panel, n = 9, 10, and 9 each from left to right). *P < 0.05 vs. aged WT HS diet–fed or KL-KO HS diet–fed mice. (B) Mean arterial BP (MBP) measured by telemetry in young WT (top), aged WT (middle), and KL-KO mice (bottom) that received NS diet, HS diet, or HS diet + KL. Arrows show the onset of the HS diet. Right panels show average MBP over a 24-hour period. n = 4 each. *P < 0.05 vs. HS diet–fed mice. Data are summarized as means ± SEM. Unpaired t tests were used for comparisons between 2 groups. For multiple comparisons, statistical analysis was performed using the Tukey-Kramer post hoc test. N.S., not significant.