Regenerative MedicineSingle Transcription Factor Switch Reverses Aging in Cells and Mouse Livers
Researchers at UCSF developed a systematic platform to identify single transcription factor (TF) perturbations that reverse aging without causing dedifferentiation. Screening 400 TF perturbations in aged human fibroblasts, they identified over a dozen candidates and validated four: overexpressing E2F3 or EZH2, and repressing STAT3 or ZFX, each reversed multiple hallmarks of cellular aging including reduced proliferation, impaired proteostasis, mitochondrial decline, and senescence. Crucially, overexpressing EZH2 alone in aged mice rejuvenated the liver — reversing age-related gene expression, reducing fat accumulation and scarring, and improving blood sugar control. These findings suggest a conserved molecular program underlying rejuvenation across species and tissues.
