FIG. 1.

Partial reprogramming with TRE-OSK leads to increased lifespan and improved frailty scores in very old mice. (a) Schematic of the constructs, virus, and injection route used in the study. (b) Kaplan–Meier curves for 124-week WT mice injected with AAV9.TRE-OSK and AAV9.hEF1ɑ-rtTA4 (both 1E12 vg/animal) through the retro-orbital route, and induced with 1 week on/off doxycycline paradigm (TRE-OSK) showed median lifespan extension of remaining life by 109% compared with either doxycycline-treated control animals (Control-Dox) or to historical published Jax data for Bl6/J mice (Jax historical). Red arrow at top indicates AAV injections. Mantel Cox Log rank test, **p < 0.05. (c) Graph shows remaining lifespan of individual mice (after injections at week 124) for data shown in (b). Two-tailed unpaired t-test; **p < 0.05. (d) FI, the compound score of 28 different health parameters (range 0–1 in 0.5 increments), showed significant reduction in FI for TRE-OSK mice at 142 weeks of age (18 weeks after injections) as compared with Control-Dox mice. Student's unpaired t-test, **p < 0.05. AAV, adeno-associated virus; FI, frailty index; WT, wild-type.