concept

OSKM

Also known as: OSKM transduction

Facts (10)

Sources

Cellular rejuvenation: molecular mechanisms and potential ... - Nature nature.com Nature Mar 14, 2023 10 facts

claimForced expression of OSKM rejuvenates multiple cellular features of dermal fibroblasts from middle-aged donors, including the transcriptome, epigenomes (specifically histone and DNA methylation), and functional characteristics.

claimA non-integrative partial reprogramming protocol using a cocktail of mRNAs carrying OSKM + LIN28 alleviates cellular aging in naturally aged human fibroblasts and endothelial cells by resetting the epigenetic clock, reducing inflammatory responses in chondrocytes, and restoring youthful regenerative responses without altering cellular identity.

claimOSKM-mediated partial reprogramming restores youthful gene expression in adipocytes, mesenchymal stem cells (MSCs), and myogenic cells, while single-cell genomics reveals that this process temporarily suppresses somatic identity programs.

claimA single period of OSKM expression in naturally aged mice alters epigenetics, transcriptomes, and metabolomes, resulting in a younger configuration in various tissues and serum, including the reversal of DNA methylation and transcriptional changes and the restoration of aging-related serum metabolites and biomarkers to youthful levels.

claimOcampo et al. reported that transient cyclic induction of OSKM in vivo ameliorates age-associated hallmarks, extends lifespan in progeroid mice, and promotes tissue repair from streptozotocin-induced pancreatic damage and cardiotoxin-caused muscle damage, without resulting in teratoma formation.

claimExpression of OSKM specifically in hepatocytes dedifferentiates adult hepatocytes into progenitor cells and promotes cell proliferation, increasing liver plasticity and regeneration.

claimHeart-specific in vivo reprogramming induces adult cardiomyocytes to a fetal state, conferring regenerative capacity and reducing myocardial infarction-induced damage.

claimOSKM + LIN28-mediated partial reprogramming in senescent human fibroblasts results in the recovery of high mobility of histone protein 1β, which is a feature characteristic of young fibroblasts.

claimTeratoma formation is a potential limitation of in vivo reprogramming, which may be caused by excessive OSKM dosage.

claimIn vivo reprogramming with short-term cyclic expression of OSKM inhibits the progression of intervertebral disc degeneration and improves senescence-associated phenotypes in ageing nucleus pulposus cells.