Partial reprogramming uses a subset of the four "Yamanaka factors" — Oct4, Sox2, Klf4, and c-Myc, the genes Shinya Yamanaka found could reset an adult cell all the way back to a stem-cell-like state. Full reprogramming erases a cell's identity entirely, which is useful for making stem cells but would be catastrophic inside a living body — a cell that forgets what kind of cell it is can become a tumor. Partial reprogramming tries to get a smaller benefit without that cost: a brief, incomplete reset that nudges a cell's epigenetic markers back toward a younger pattern while it still remembers it's a skin cell, or a neuron, or whatever it was.
One detail matters more than it might seem: the exact recipe differs by study. The mouse lifespan work below uses all four factors (OSKM), delivered in short pulses to the whole body specifically to avoid full reprogramming. The eye-specific work and the one human trial that exists use only three factors (OSK), permanently leaving out c-Myc — a gene strongly linked to cancer — and apply it to a single contained tissue rather than the whole body. These are related but genuinely different approaches, evaluated for different things, and this page tries to keep that distinction clear throughout rather than blurring it the way press coverage often does.
The foundational result came from a mouse model of Hutchinson-Gilford progeria, a disease causing drastically accelerated aging. Cyclic, short pulses of OSKM reduced signs of aging in multiple tissues and extended average lifespan from about 18 to 24 weeks, with no tumors even after 35 rounds of dosing (Ocampo et al., 2016). The same paper found partial reprogramming also improved tissue regeneration — more pancreatic insulin-producing cells, more muscle repair capacity — in normal, non-progeric aged mice, though it didn't test whether that translated into a longer lifespan for them.
A follow-up study closed that gap. A single 2.5-week pulse of OSKM, given early in life, extended a late-life lifespan measure by 23.7% in progeroid mice and by 16.8% in genetically normal mice — the first demonstration that reprogramming extends lifespan in mice without a disease driving their aging (Alle et al., 2022). Worth noting: neither of these studies used the NIH's multi-site Interventions Testing Program that rapamycin and acarbose were tested through, so the bar of evidence here is earlier-stage than for those two.
There is no human trial testing partial reprogramming for lifespan, and realistically there won't be one for a very long time, for the same reason rapamycin has none — that trial would take decades. The one human trial that exists is testing something much narrower.
ER-100, from Life Biosciences (co-founded by David Sinclair, whose lab produced the OSK eye research below), delivers OSK directly into the eye to treat two causes of vision loss: glaucoma and NAION. It uses the 3-factor version specifically, with no c-Myc, and the genes are wired to a doxycycline-controlled switch so dosing can be started or stopped with a pill. The FDA cleared it for human testing in January 2026, and the first participant was dosed on 9 June 2026 — the first time partial reprogramming had been given to a human being. This is a Phase 1 trial: its job is to check safety and tolerability, not to prove it works. As of this writing (1 October 2026), Life Biosciences has announced it will present the trial's first interim data at a conference, but the actual results aren't public yet — worth checking back on.
The mouse work behind this human trial is separate from the lifespan studies above. Using OSK delivered directly into the eyes of mice, a 2020 study restored youthful gene-expression patterns in retinal neurons, roughly doubled the number of nerve cells that survived an optic nerve injury, and reversed vision loss in both a glaucoma model and in naturally aged mice (Lu et al., 2020). This is the direct scientific basis for ER-100 — but it's a study about eye tissue function, not lifespan.
| Study | Factors | Organism / tissue | Result | Notes |
|---|---|---|---|---|
| Ocampo et al. 2016 | OSKM | Mice, whole body (progeria) | Lifespan +33% (18→24 wks) | Also improved regeneration in normal aged mice |
| Alle et al. 2022 | OSKM | Mice, whole body (progeria + normal) | Lifespan +23.7% / +16.8% | First lifespan result in genetically normal mice |
| Lu et al. 2020 | OSK | Mice, eye only | Vision restored, nerve regrowth | Not a lifespan study |
| ER-100 (ongoing) | OSK | Humans, eye only | Safety trial, interim data pending | Not testing lifespan or whole-body aging |
The central open problem is the one this page keeps returning to: the mouse lifespan evidence and the human trial use different tools for different jobs, and nobody has tested the human-relevant version (OSK, no c-Myc) for whole-body lifespan in animals, or the lifespan-tested version (OSKM, with c-Myc) in any human tissue. Tumor risk is the reason for that gap — c-Myc is excluded from human use specifically because of its cancer association, which means the approach shown to extend mouse lifespan isn't the one anyone considers safe enough to try systemically in people yet. Durability is also unresolved: whether a single early-life pulse's benefit (seen in Alle et al.) actually lasts a normal human lifetime, or whether periodic re-dosing would be needed, isn't known from a few years of mouse follow-up.
Would the OSK (no c-Myc) version used in humans extend lifespan in mice if tested systemically?
This hasn't been tested. It's the single biggest missing link between the mouse lifespan data and the human trial.
Would OSKM reprogramming survive a multi-site replication like the ITP?
Both lifespan studies came from single labs. Rapamycin and acarbose only became trustworthy once replicated at three independent sites — this hasn't had that test yet.
What will ER-100's interim safety data actually show?
Announced for presentation as of October 2026 but not yet public. This is the most concrete near-term update to watch for.
Does a brief early-life pulse's benefit last, or fade with time?
Alle et al. followed mice into old age after a single early treatment, but it's one study. Whether the effect is durable across a full natural lifespan, or would need repeat dosing, is unresolved.
In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming
Ocampo et al., Cell, 2016 · Mice (progeria)
Supports. Cyclic short pulses of OSKM extended average lifespan from about 18 to 24 weeks in a progeria model, with no tumors after 35 dosing cycles. Also improved pancreatic and muscle regeneration in normal aged mice, though lifespan wasn't tested in that group. The foundational result for this whole field.
A single short reprogramming early in life initiates and propagates an epigenetically related mechanism improving fitness and promoting an increased healthy lifespan
Alle et al., Aging Cell, 2022 · Mice (progeria and genetically normal)
Supports. A single 2.5-week OSKM pulse at 2 months of age extended late-life lifespan by 23.7% in progeroid mice and 16.8% in genetically normal mice — the first time reprogramming was shown to extend lifespan without a disease accelerating aging in the first place.
Reprogramming to recover youthful epigenetic information and restore vision
Lu et al., Nature, 2020 · Mice (eye only)
Mixed. Used OSK (not OSKM) delivered directly to retinal neurons. Restored youthful DNA methylation patterns, roughly doubled surviving nerve cells after optic nerve injury, and reversed vision loss in a glaucoma model and in naturally aged mice. A real, replicated-mechanism result, but about eye tissue function specifically, not lifespan — the direct basis for the ER-100 human trial below.
ER-100 Phase 1 trial (NCT07290244)
Life Biosciences · Ongoing · Humans, eye only
Pending. A safety and tolerability trial of OSK gene therapy injected into the eye, for glaucoma and NAION. FDA-cleared January 2026, first patient dosed June 2026. As of October 2026, interim data has been announced for presentation at a conference but is not yet public. This trial is not testing lifespan or whole-body aging — only safety and vision outcomes in a single tissue.