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Publication : Multi-omic rejuvenation of naturally aged tissues by a single cycle of transient reprogramming.

First Author  Chondronasiou D Year  2022
Journal  Aging Cell Volume  21
Issue  3 Pages  e13578
PubMed ID  35235716 Mgi Jnum  J:322938
Mgi Id  MGI:7257064 Doi  10.1111/acel.13578
Citation  Chondronasiou D, et al. (2022) Multi-omic rejuvenation of naturally aged tissues by a single cycle of transient reprogramming. Aging Cell 21(3):e13578
abstractText  The expression of the pluripotency factors OCT4, SOX2, KLF4, and MYC (OSKM) can convert somatic differentiated cells into pluripotent stem cells in a process known as reprogramming. Notably, partial and reversible reprogramming does not change cell identity but can reverse markers of aging in cells, improve the capacity of aged mice to repair tissue injuries, and extend longevity in progeroid mice. However, little is known about the mechanisms involved. 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.
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