Partial Cellular Reprogramming

What the evidence says

Partial reprogramming transiently expresses some Yamanaka factors in an attempt to reset age-associated cellular patterns without pushing cells fully into pluripotency and erasing their identity. Cyclic OSKM expression improved aging markers and extended lifespan in a progeroid mouse model, which is not equivalent to normal aging.^[1]

In mouse retinal ganglion cells, OSK expression restored younger DNA-methylation patterns, promoted axon regeneration, and improved visual function in injury, glaucoma, and aging models. This is a striking tissue-specific animal result, not proof of general rejuvenation.^[2]

Other normally aged mouse studies report younger molecular signatures across selected tissues after transient or cyclic reprogramming. Protocols, factor combinations, exposure, tissues, and outcome assays differ enough that one result cannot define a universal intervention.^[3][4]

A small company-linked AAV-OSK study in very old male mice reported a 109% increase in remaining median lifespan. The small sample, male-only design, late-life survival framing, and lack of independent replication make it hypothesis-generating rather than definitive.^[5][6]

ER-100 became the first registered human OSK program in 2026: a phase 1 study delivering a doxycycline-controlled AAV therapy to one eye in glaucoma or ischemic optic neuropathy. Its primary purpose is safety; it has no posted efficacy result and provides no evidence for systemic longevity. Central risks include loss of cell identity, uncontrolled growth, immune or vector toxicity, tissue-specific dosing, and control of gene expression.^[7][6]