Effect of the microbiota on mice in vivo age reprogramming
The induction of cellular reprogramming by forced expression of the transcription factors OCT4, SOX2, KLF4, and C??YC (OSKM) has been shown to allow the dedifferentiation of somatic cells and ameliorate age-associated phenotypes in multiple tissues and organs. Yet to date, the benefits of long-term in vivo reprogramming are limited by the occurrence of detrimental side??ffects. Here, using complementary genetic approaches, we demonstrated that continuous induction of the reprogramming factors in vivo leads to hepatic and intestinal dysfunction resulting in decreased body weight and premature death. By generating a novel transgenic reprogrammable mouse strain, which avoids OSKM expression in both liver and intestine, we drastically reduced the early lethality and adverse effects associated with in vivo reprogramming and induce a decrease in organismal biological age. This new reprogramming mouse strain, which allows safe and long-term continuous induction of OSKM, might enable better understanding of in vivo reprogramming, as well as maximize its potential effects on rejuvenation and regeneration.