In vivo partial reprogramming alters manifestation of age-associated molecular changes in aging mice (7 months; long-term treatment)

Various length of in vivo 4F (four Yamanaka factors) partial reprogramming protocols were performed to evaluate effects of longer-term partial reprogramming in physiologically aging wild-type mice. Here, long-term (7 months) partial reprogramming was induced and transcriptional changes in various tissues were compared to age-matched, untreated mice. Mice carrying one copy of OSKM (Sox2, Oct4, Klf4, and c-Myc) polycistronic cassette and the rtTA transactivator (C57BL/B6 background) were treated with 1mg/ml doxycycline in drinking water for 2 days followed by 5 days of withdrawal per week. Treatment was performed for 7 months started at 15 months of age and ending at 22 months. Untreated C57BL/B6 only, 22-month-old mice were used as controls. RNA was extracted from skin, kidney, lung, liver, spleen, skeletal muscle and RNA-seq was performed to evaluate transcriptional changes.