Fig. 1. STING promotes low-grade inflammation and functional decline in aged mice.
a,b, mRNA expression levels of proinflammatory genes and ISGs (a) and RNA-seq analysis (b) of human WI-38 fibroblasts irradiated (12 Gy, IR) or maintained at 5% O2 (Ctrl), and treated with H-151 (daily, 0.5 μM) or DMSO for 10 days when senescent (day 10 to 20). The relative expression (RE) was measured for each experiment (n = 6) relative to the induction level in the irradiated DMSO condition (a). b, The top 50 genes most upregulated after irradiation and suppressed after H-151 treatment (n = 4 experiments) (top), and a gene set enrichment analysis showing the fold enrichment based on the above list of genes (bottom). c, Schematic of the treatment of wild-type (WT) aged mice with H-151 related to data shown in d and f–h. d,e, Kidney mRNA expression levels of proinflammatory genes and ISGs in young (n = 4) and aged mice treated with or without H-151 (n = 6) (d) and of young (n = 3), aged WT (n = 4) and Sting1−/− mice (n = 6) (e). Expression was measured relative to the average of aged vehicle-treated (d) or aged WT (e) mice. f,g, The physical condition of aged mice treated with or without H-151 (n = 7), evaluated by grip strength (f) and treadmill running distance (g). h, Cognitive function tests (n = 11 mice) were evaluated using the Morris water maze test (left, latency to reach the platform over multiple days) and fear conditioning (right, percentage of time spent freezing. P = 3 × 10−5. Data are mean ± s.e.m. P values were obtained using two-sided paired ratio Student’s t-tests (a), two-sided unpaired Student’s t-tests (f–h (right)), one-way analysis of variance (ANOVA) followed by Tukey’s multiple-comparison test (d and e) and ordinary two-way ANOVA (h, left).