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. 2021 Apr 20;10:e61138. doi: 10.7554/eLife.61138

Figure 4. Development and validation of an AAV approach for systemic delivery of Klotho.

(A) Changes in circulating Klotho levels measured via ELISA in young (3–6 months), middle-aged (10-14 months), old (21-24 months), and oldest-old (27-29 months) male (N = 41), and female (N = 47) mice (one-way ANOVAs). (B) Changes in circulating FGF23 levels in male (N = 20) and female (N = 39) mice. Red symbols represent undetectable levels and were set to zero (Kruskal-Wallis tests, KO values were excluded from statistical analysis). (C) Schematic of the AAV-Klotho plasmid design. (D) Liver expression of AAV vector genomes quantified via qPCR (N = 33, Kruskal-Wallis test). (E) Circulating Klotho levels measured via MSD-ELISA in young female (N = 33) mice injected with AAV-Klotho at varying doses (Kruskal-Wallis test). (F) Gene count normalized to library size for Klotho in the gastrocnemius muscle of female mice treated with GFP and AAV-Kl (N = 20, one-way ANOVA). (G,H,I) Serum concentration levels for insulin (N = 29), cholesterol (N = 35), and glucose (N = 20) in GFP- and Kl-treated female mice (one-way ANOVA). All data presented as mean ± SD (*p<0.05, **p<0.01, ***p<0.001, ****p<0.0001).

Figure 4—source data 1. Raw Data for Figure 4A-B, D-I, and Figure 4—figure supplement 1.

Figure 4.

Figure 4—figure supplement 1. Quantification of circulating lipid metabolites in mice receiving AAV-Kl treatment versus controls.

Figure 4—figure supplement 1.

Circulating phospholipids (N = 20), NEFA (N = 20), and triglycerides (N = 20) in young (3–6 months), old (21-24 months), and oldest-old (27-29 months) female mice receiving AAV-GFP or AAV-Kl​.