GSE190985
In vivo partial reprogramming alters manifestation of age-associated molecular changes in aging mice (10 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 (10 months) partial reprogramming was induced and transcriptional changes in various tissues were compared to age-matched, untreated mice. Overall design: 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 10 months started at 12 months of age and ending at 22 months. Untreated 4F, 22-months-old mice were used as controls. To identify and exclude doxycycline effects, C57BL/B6 mice were treated with doxycycline for 5 months starting at 20-months-old and ending at 25-months-old. Untreated C57BL/B6 mice of 26 months were used as controls. RNA was extracted from skin, kidney, lung, liver, spleen, skeletal muscle and RNA-seq was performed to evaluate transcriptional changes.