Fig. 1
From: Targeting of NAT10 enhances healthspan in a mouse model of human accelerated aging syndrome
Oral administration of Remodelin decreases weight loss in progeria mice. a, b Cells were treated with DMSO or with 1 µM Remodelin for 7 days. a Left: Representative immunofluorescence images of skin fibroblasts from LmnaG609G/G609G mice showing the accumulation of the DNA double-strand break marker gamma H2AX (γH2AX) ( blue) and characteristic nuclear shape abnormalities, observed by DAPI staining. All images were acquired with the same microscope intensity settings. Scale bar 20 µm. Right: Quantification of γH2AX positive cells and cells with misshapen nuclei (>100 cells/n = 3 independent cell lines; mean ± s.d.; n.s. not significant; *p < 0.05, **p < 0.01, ***p < 0.001, two-tailed Student’s t-test). b Western blotting analysis of γH2AX levels (quantified in the right panel) in skin fibroblasts from the indicated genotypes. c,d Pharmacokinetic analyses of Remodelin in mice treated via oral (PO; n = 3) or intravenous (IV; n = 3) delivery; mean ± s.e.m. F absolute bioavailability (%). e Tissues were collected after 2 weeks of daily PO administration of the indicated Remodelin concentration and 1 h after the last dosing. Remodelin was quantified by mass spectrometry in the heart and the skeletal muscle (n = 3); mean ± s.e.m. f Survival based on 20% body weight loss, showing a 25% increase in Kaplan–Meier area under the curve in Remodelin-treated LmnaG609G/G609G mice, as compared to vehicle-treated mice (see Supplementary Table 3); (*Log-rank Mantel-Cox test; Chi-square 5.992). Due to animal welfare regulations, mice had to be killed when they had lost 20% of their body weight, compared to their individual weight maxima (end-point). However, at this defined end-point, Remodelin-treated mice displayed considerably better health, compared to the vehicle-treated controls (see supplementary movies and pathology assessments in Fig. 2)
