a, 3× cells were treated with L1 shRNA or with 3TC for 48 h as described in Extended Data Fig. 5g,i. Effects on the IFN-I response were determined by RT–qPCR, ELISA or immunoblotting. For gel source data, see Supplementary Fig. 1. b, Cells were serially passaged into replicative senescence with 3TC (10 μM) present throughout, as in Fig. 3f, and expression of the CDK inhibitors p21 and p16 was assessed by RT–qPCR. c, Senescent cells were treated with shRNAs against CGAS or STING between 12 and 16 weeks of senescence (as described in Extended Data Fig. 5l), and expression of IFN-I response genes (IFNA, IRF7 and OAS1) was determined. d, cGAS and STING knockdowns were performed with shRNAs in 3× cells (as in c), and expression of IFN-I genes was examined by RT–qPCR. e, cGAS and STING were knocked down in senescent cells with shRNAs (as in c), and expression of SASP response genes (IL1B, CCL2, IL6 and MMP3) was assayed by RT–qPCR. f, g, The activity of K-9 was compared with 3TC in senescent and 3× cells. Senescent cultures were treated between 12 and 16 weeks (as in Fig. 3b) and 3× cultures for 48 h (as in a). Effects on the expression of IFN-I genes (IFNA, IRF7 and OAS1) and SASP genes (IL1B, IL6 and MMP3) was assessed by RT–qPCR. n = 3 independent experiments. Data are mean ± s.d. *P ≤ 0.05, **P ≤ 0.01, unpaired two-sided t-test. Exact P values can be found in the accompanying Source Data.