Fig. 4. Increases in the PARP1-DBC1 complex and DNA damage with age are reversed by NMN, a precursor to NAD⁺.

(A and B) NAD⁺ concentrations and PARP1-DBC1 interactions in livers of young and old mice (6 versus 22 months, n = 3 per group). (C) γH2AX-positive cells (red arrow) in the livers of young (6 months, Y) and old (30 months, O) mice (n = 3 per group) treated for 7 days with vehicle [phosphate-buffered saline (PBS)] or NMN (500 mg/kg per day intraperitoneally, n = 3 per group). Scale bars, 50 μm. (D and E) NAD⁺ concentrations and PARP1-DBC1 interactions in the livers of old mice (22 months) treated as in (C). (F) PARP1 activity in young (6 months, n = 4) and old (26 ± 4 months, n = 8 per group) mice. (G) PARP1 activity in 18- to 20-month-old DBC1 knockout mice livers (n = 3 or 4). (H) γH2AX abundance in the livers of 26-month-olds after irradiation (IR) [7.5 grays (Gy), ¹³⁷CsCl], treated as in (C) (n = 3 per group). (I) Blood counts of 23-month-olds on the 7th or 8th day after irradiation (n = 10 per group). See fig. S18, A and B. (J) Blood metrics of 4-month-olds given a single oral dose of NMN (2000 mg/kg) 1 hour after irradiation (8 Gy, ¹³⁷CsCl), followed by another 7 days of treatment (2000 mg/kg per day, n = 5 to 8 per group). Veh, vehicle. See fig. S18C. Errors bars indicate SEM; unpaired two-tailed t test [(A), (B), (D), (E), and (G)], one-way ANOVA [(C), (F), and (H)], Sidak’s post-hoc correction, Mann-Whitney U-test [(I) and (J)]. *P < 0.05, **P < 0.01, ****P < 0.0001.