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. 2014 Dec 6;14(1):139–147. doi: 10.1111/acel.12279

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© 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Rapid reversal of aging features in CAG-rtTA3 mice following p16 de-induction. (a) Top row: a noninducing littermate mouse at D80 of Dox treatment (different angles). Middle row: a CAG-rtTA3:TetOp16 mouse at D80 of Dox treatment. Lower row: the same CAG-rtTA3:TetOp16 mouse following 4 weeks of Dox withdrawal. Note dramatic recovery in body hair and skin wrinkling, filling out of face and eyes, and straightening of whisker hairs. Only the hair on the ventral trunk lagged (center), and the eyes remained sunken. (b) Left: littermate female CAG-rtTA3:TetOp16 mice (‘inducers’ F1-3) and wild-type or singly transgenic mice (‘noninducers’ F4-7) were treated with Dox from D20-40. Mice were weighed weekly for 2 weeks and then 4 weeks after Dox withdrawal (X-axis: days). Inducers showed a dramatic rebound in weight (Y-axis: g) within the first week. Right: littermate male inducers (M1-2) and noninducers (M3-6) were treated with Dox D20-80, and then Dox was withdrawn. Inducers showed a prompt recovery in weight within 2–4 weeks. The slope of weight gain was greater in the mice with prior p16 induction (P = 0.03).