Open AccessMulti‐omic rejuvenation of naturally aged tissues by a single cycle of transient reprogramming
Author(s) -
Chondronasiou Dafni,
Gill Diljeet,
Mosteiro Lluc,
Urdinguio Rocio G.,
BerenguerLlergo Antonio,
Aguilera Mònica,
Durand Sylvere,
Aprahamian Fanny,
Nirmalathasan Nitharsshini,
Abad Maria,
MartinHerranz Daniel E.,
StephanOtto Attolini Camille,
Prats Neus,
Kroemer Guido,
Fraga Mario F.,
Reik Wolf,
Serrano Manuel
Publication year - 2022
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.13578
Subject(s) - biology , reprogramming , klf4 , sox2 , transcriptome , dna methylation , induced pluripotent stem cell , microbiology and biotechnology , epigenetics , somatic cell , metabolome , cell , genetics , metabolomics , embryonic stem cell , bioinformatics , gene expression , gene
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.