Progression vs. recovery of aging features. CMV-rtTA:TetO-p16 littermates treated with Dox d20-40 were divided into 2 groups. Dox was sustained in one and withdrawn in the other. Mice were sacrificed at d80. (a) Sustained Dox treatment d20-80 results in persistent defects. Note the thin hair, hunched posture, thin body, and sunken eyes in representative mice (a1, all); malocclusion of the incisors, with resulting overgrowth (alll, 5/17 mice); and cataracts (alV, bilateral, confirmed by histology; 2/17 mice). (b) Back hair density (mg cm−2) in bitransgenic mice (Bi) treated with Dox d20-80 (N = 14) and Bi mice treated with Dox d20-40 and sacrificed at d80 (N = 6) were normalized to that of their wild-type and singly transgenic littermate controls (Con) treated with Dox d20-80 (N = 12) and depicted as mean ± SD (percentages relative to controls listed). Hair density of Bi d20-40sac80 mice was significantly greater than in Bi d20-80 mice (P = 0.02) and did not differ significantly from control mice. (c) Increase in myeloid to lymphoid ratio with sustained Dox treatment d20-80 in bitransgenic mice (P = 0.01 compared to control d20-80 mice), ameliorated by discontinuing Dox at d40 (P = 0.02 compared to Bi d20-80 mice). Results shown are means ± SD from 3 to 5 mice, except the control d20-180 results, which are mean ± range from two mice.