Extended Data Fig. 7: Pharmacological inhibitors of LINE-1 reverse transcription or STING signaling attenuate cardiac aging phenotypes in aged mice.
From: Targeting age-related LINE-1 activation alleviates cardiac aging
a, Representative pulsed-wave Doppler (PWD, upper) and tissue Doppler imaging (TDI, lower) of mice of 10 weeks old (10 wk), 48 weeks old (48 wk), 72 weeks old (72 wk), 72 weeks old and received 3TC treatment beginning at 48 weeks of age (72 wk + 3TC), and 72 weeks old and received H-151 treatment beginning at 48 weeks of age (72 wk + H-151). Quantitative data on the ratio of early-diastolic transmitral flow velocity to early-diastolic mitral annular velocity (E/e′) are shown to the right. n = 5 mice for the first four groups and 3 for 72 wk + H-151 group. b, Relative LINE-1 DNA abundance in the hearts from each group. n = 6 mice per group. c, qPCR analysis showing LINE-1 ORF1 and ORF2 transcript levels in the hearts from each group. n = 5 mice per group. d, Heatmap showing transcript levels of SINE-B1, SINE-B2, MuLV, MMERVK10C, and MERVL in the hearts from each group. n = 5 mice per group. e, Immunohistochemical analysis of IL-1β (upper), TNF (middle), and F4/80 (lower) in the hearts from each group. Scale bar, 25 µm. Quantitative data on relative IL-1β and TNF signal intensities and the proportion of F4/80-positive cells are shown to the right. n = 6 mice per group. f, Immunohistochemical analysis of p21 (upper) and p16 (lower) in mouse hearts from each group. Brown color in the nuclei indicates the cells positive for p21 and p16. Scale bar, 25 µm. Quantitative data on the proportion of positive cells are shown to the right. n = 6 mice per group. Data are presented as mean ± SEM with individual data points indicated (a-c and e-f) or heatmap (d). Groups were compared using one-way ANOVA and post hoc Dunnett′s test. ns, not significant, *p < 0.05, **p < 0.01, ***p < 0.001 compared to 72 wk group.
