Thyroid state in skeletal muscle of progeroid and naturally aged mice.

<p>T3 concentrations (A) and activities of D2 (B) and D3 (C) in muscle of 15-day-old WT and XAA (Csbm/m/Xpa-/-) mice (n = 3/group). T4 (D) and T3 (E) concentrations and activities of D2 (F) and D3 (G) in muscle of 18-week-old WT and MAA (Ercc1-/Δ-7) mice (n = 3/group). T4 (H) and T3 (I) concentrations and activities of D2 (J) and D3 (K) in muscle of 26-, 104-, and 130-week-old WT mice (n = 3-5/group). Values represent mean ± SE per group. * P < 0.05</p

Thyroid state in serum of progeroid and naturally aged mice.

<p>Serum T4 (A) and T3 (B) concentrations in 7-, 12-, 15-, and 18-day-old WT (squares) and XAA (Csbm/m/Xpa-/-) mice (circles) (n = 3/group). Serum T4 (C) and T3 (D) concentrations in 4-, and 18-week-old WT (black bars) and MAA (Ercc1-/Δ-7) (white bars) mice (n = 3/group). Serum T4 and T3 concentrations in 26-, 104-, and 130-week-old WT male mice (n = 3-4/group) (E). Serum TSH levels in 15-day old WT and XAA (Csbm/m/Xpa-/-) mice (F) and in 26-, 104-, and 130-week-old WT male mice (G). Values represent mean ± SE per group. * P < 0.05; ** P < 0.01; *** P < 0.001; # P = 0.054.</p

Thyroid state in brains of progeroid and naturally aged mice.

<p>Homogenates of whole brain or hemispheres were used. T4 (A) and T3 (B) concentrations in brains of 7-, 12-, 15-, and 18-day-old WT (squares) and XAA (Csbm/m/Xpa-/-) mice (n = 3/group). Activities of D2 (C) and D3 (D) brains of 7-, 12-, 15-, and 18-day-old WT and XAA (Csbm/m/Xpa-/-) mice (n = 3/group). T4 (E) and T3 (F) concentrations and D3 activity (G) in brains of 4-, and 18-week-old WT (black bars) and MAA (Ercc-/Δ-7) (white bars) mice (n = 3/group). It was not possible to measure D2 activity due to technical constraints. Values represent mean ± SE per group. * P < 0.05; ** P < 0.01; *** P < 0.001.</p

Liver D1 and D3 activity in DEHP-treated WT mice.

<p>Activities of D1 (A) and D3 (B) in 10-wk-old WT animals after exposure or not to subtoxic doses of the pro-oxidant DEHP for 2, 12 and 39 weeks. Values represent mean ± SE per group (n = 5). * P < 0.05; ** P < 0.01.</p

Schematic representation of the survival response.

<p>Several types of stress (e.g. DNA damage and aging) can trigger a differential response in various tissues. This response ensures decreased TH signalling in liver and kidney, while it preserves TH signalling in brain, muscle and heart.</p

Gene expression changes in livers from progeroid and normal aging mice.

<p>Gene expression of the T3-responsive genes Dio1 and Thrsp in 18-day-old XAA (Csbm/m/Xpa-/-) (A) and 16-week-old MAA (Ercc1-/Δ-7) mice (B). * P < 0.005; # P = 0.12. Expression profiling of a set of known T3-responsive genes in 15-day-old XAA (Csbm/m/Xpa-/-) (C) and 16-week-old MAA (Ercc1-/Δ-7) mice (D) mutants compared to age-matched controls. Values represent mean ± SE * P < 0.05; ** P < 0.005; $ P < 0.1; # P = 0.12.</p

Histological examination of haematoxylin/eosin-stained thyroid glands of 15-day-old WT and XAA (Csbm/m/Xpa-/-) (A) and 16-week-old WT and MAA (Ercc1-/Δ-7) (B) mice (all magnifications 10x).

<p>The thyroid follicles (denoted by asterisk) surrounded by thyrocytes (denoted by arrow) are similar between WT and progeria models.</p

Thyroid state in liver of progeroid and naturally aged mice.

<p>T4 (A) and T3 (B) concentrations in livers of 7-, 12-, 15-, and 18-day-old WT (squares) and XAA (Csbm/m/Xpa-/-) (circles) mice (n = 3/group; each time point of Csbm/m/Xpa-/- mice represents pooled tissues). Activities of D1 (C) and D3 (D) in livers of 7-, 12-, 15-, and 18-day-old WT and XAA (Csbm/m/Xpa-/-) mice (n = 3/group). T4 (E) and T3 (F) concentrations and D1 activity (G) in livers of 4-, and 18-week-old WT (black bars) and MAA (Ercc1-/Δ-7) (white bars) mice (n = 3/group). D3 mRNA expression in livers of 13-week-old and 130-week-old mice (H). D1 (black bars) (I) and D3 (grey bars) (J) activities in livers of 26-, 52-, and 104-week-old WT mice (n = 5/group). Values represent mean ± SE per group. * P < 0.05; ** P < 0.01; *** P < 0.001; # P = 0.051.</p