Epigenetics
Transient reprogramming rejuvenates fibroblasts ~30 years
Open access · cc by · source: Europe PMC
Maturation-phase transient OSKM expression (MPTR) rewinds transcriptome and epigenome aging clocks by ~30 years while cells reacquire fibroblast identity and youthful collagen/migration traits.
Key findings
Cells temporarily lose then regain fibroblast identity (enhancer memory). Transcriptome rejuvenated ~30 years; epigenome similarly (H3K9me3; methylation clock). Effects exceeded prior transient protocols. Fibroblasts produced youthful collagen and partially recovered migration speed—showing rejuvenation can be separated from full pluripotency.
Methodology
Gill et al. developed MPTR: express Yamanaka factors until maturation-phase rejuvenation, then withdraw. Applied to dermal fibroblasts from three middle-aged donors (ages 38/53/53), targeting the day 10–17 window suggested by clock trajectories, then measured transcriptome clocks, DNA methylation clocks, H3K9me3, collagen, and migration.
Limitations
In vitro fibroblast results may not translate to safe in vivo rejuvenation. Donor n=3 is small; long-term genomic stability/tumor risk not fully settled.
How this study connects
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