Research Paper Volume 11, Issue 18 pp 7746—7779

Inadequate control of thyroid hormones sensitizes to hepatocarcinogenesis and unhealthy aging

Figure 1. High or low TH levels compromise murine healthspan and lifespan. (A) Circulating T4 levels at 21 days of age. n = 5 Wt, n = 5 Pax8 +/-, n = 5 Pax8 -/-, n = 5 Wt T4, n = 5 Pax8 +/- T4, n = 3 Pax8 -/- T4. Two-way ANOVA. (B) Kaplan-Meier survival curve. n = 58 Wt, n = 20 Pax8 +/-, n = 10 Pax8 -/-, n = 15 Wt T4, n = 20 Pax8 +/- T4, n = 5 Pax8 -/- T4. Survival log rank test. (C) Basal daily energy intake in 5-weeks old mice. n = 5 Wt, n = 4 Pax8 +/-, n = 3 Pax8 -/-, n= 3 Wt T4, n = 3 Pax8 +/- T4, n = 3 Pax8 -/- T4 (the “n” reflects the number of cages). Two-way ANOVA. (D) Body weight at 21 days of age. n = 21 Wt, n = 15 Pax8 +/-, n = 5 Pax8 -/-, n = 11 Wt T4, n = 11 Pax8 +/- T4, n = 4 Pax8 -/- T4. Two-way ANOVA. (E) Circulating T4 levels at 8 months of age. n = 11 Wt, n = 5 Pax8 +/-, n = 7 Wt T4, n = 5 Pax8 +/- T4. Two-way ANOVA. (F) Circulating T4 levels at 24 months of age. n = 8 per group. T-test two tailed. (G) Body weight during longevity assay. n = all available mice of longevity assay (panel B). One-way ANOVA or ANOVA on ranks if distribution is not normal. * on months 6-17 and 21-28. & on months 12-18. # on months 3, 5-8 and 10-18. x on months 3-12. (H) Representative photographs and hematoxylin and eosin staining of liver tissue from Wt and Pax8 +/- mice at necropsies. Wt liver exhibits normal hepatic parenchyma with acinar architecture. Pax8 +/- liver displays primary liver epithelial neoplasms (T) with disorganized architecture and inflammatory infiltrate (II). Scale bar 100 um. n = 4 per group. See also Supplementary Figure 1K. (I) Histological analysis of liver tissue by hematoxylin and eosin staining at 21 days of age. n = 4 Wt, n = 5 Pax8 +/-, n = 5 Pax8 -/-, n = 5 Wt T4, n = 5 Pax8 +/- T4, n = 3 Pax8 -/- T4. Scale bars; top: 200 μm; down: 100 μm. Data are represented as the mean ± SEM. * p-value < 0.05 between Wt mice and Pax8 +/- mice. + p-value < 0.05 between Wt mice and Pax8 -/- mice. & p-value < 0.05 between Wt mice and Wt T4 mice. # p-value < 0.05 between Wt mice and Pax8 +/- T4 mice. x p-value < 0.05 between Wt mice and Pax8 -/- T4.