Figure 4. Senescent cell clearance improves pulmonary and physical health in bleomycin injury.

(a) Ink-Attac transgenic mice receiving bleomycin (Bleo) through aerosolized intratracheal instillation were randomized to receive vehicle (Veh), AP or DQ and compared with PBS-exposed mice treated with Veh. Treatment timeline is indicated. Mice were killed 3 weeks post challenge, a time point at which lung fibrosis peaks¹⁵ (haematoxylin and eosin (H&E) panels top: PBS, bottom: Bleo). Lung expression of (b) p16, (c) SASP factors Mcp1, Il6, Tnfα, Mmp3, Mmp12 and profibrotic factors Col1a1 and Tgfβ were quantified by RT–PCR and are expressed relative to Hprt levels. (d) Whole-body plethysmography was used to assess enhanced pause (Penh), an indirect measure of airway resistance. (e) Lung compliance was ascertained by FlexiVent forced oscillation technique at endpoint. (f) Twenty-one-day body weight (BW) was compared with baseline body weight. (g) Exercise capacity was assessed through a treadmill test; distances ran to exhaustion are depicted (mean±s.e.m.; PBS+Veh n=13 (grey), Bleo+Veh n=8 (red), Bleo+AP n=12 (blue), Bleo+DQ n=13 (yellow); linear regression model; ***P<0.0005, **P<0.005, *P≤0.05, ^¥P=0.08 and ^#P=0.1).