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Multi-omic rejuvenation of naturally aged tissues by a single cycle of transient reprogramming
Dafni Chondronasiou 1, Diljeet Gill 2, Lluc Mosteiro 3, Rocio G Urdinguio 4 5 6 7 8, Antonio Berenguer-Llergo 1, Mònica Aguilera 1, Sylvere Durand 9 10 11, Fanny Aprahamian 9 10 11, Nitharsshini Nirmalathasan 9 10 11, Maria Abad 12, Daniel E Martin-Herranz 13, Camille Stephan-Otto Attolini 1, Neus Prats 1, Guido Kroemer 9 10 11 14 15 16, Mario F Fraga 4 5 6 7 8, Wolf Reik 2 17 18 19, Manuel Serrano 1 20
...Here, we have studied changes in the DNA methylome, transcriptome, and metabolome in naturally aged mice subject to a single period of transient OSKM expression. We found that this is sufficient to reverse DNA methylation changes that occur upon aging in the pancreas, liver, spleen, and blood. Similarly, we observed reversion of transcriptional changes, especially regarding biological processes known to change during aging. Finally, some serum metabolites and biomarkers altered with aging were also restored to young levels upon transient reprogramming. These observations indicate that a single period of OSKM expression can drive epigenetic, transcriptomic, and metabolomic changes toward a younger configuration in multiple tissues and in the serum.