Peptide & experimental
Partial reprogramming (Yamanaka factors)
Gene therapy procedure using transcription factors, experimental, not approved · Yamanaka factors, OSKM, OSK, cellular reprogramming, epigenetic reprogramming, ER-100
Four genes turn a mature body cell back into a stem cell. If you switch them on briefly and off again in time, tissues in mice become younger instead of turning into tumors. Since March 2, 2026, this has been tested in humans for the first time — in the eye, in 18 participants.
In short
Partial reprogramming means switching on the four Yamanaka factors Oct-4, Sox-2, Klf-4 and c-Myc only briefly and switching them off again before a cell loses its identity. In animals this works: a mouse with premature aging lived 24 instead of 18 weeks on average, and in retinal cells nerve fibers regrew and vision returned. The risk is not an operating accident but the core of the method — if the process runs all the way through, teratomas form. In humans, exactly one study with the agent ER-100 has been running since March 2, 2026, not randomized, not blinded, and it measures safety, not eyesight and not aging. There is nothing to buy.
What gets reprogrammed
In 2006, Shinya Yamanaka showed that four genes are enough to turn a skin cell back into a stem cell: Oct-4, Sox-2, Klf-4 and c-Myc. The cell forgets what it is. This earned the Nobel Prize in 2012.
The same paper states the problem: if such cells are injected into mice, tumors form. That was known from the start.
Why full throttle does not work
In 2013, a paper in Nature showed what happens when the four factors are briefly switched on in the living animal: teratomas in the stomach, intestine and kidney. In 2014, a paper in Cell, with Yamanaka among the authors, followed with the more uncomfortable finding: even an interrupted pulse is enough for tumors, via methylation rather than mutation.
The tumor is not the price of a mistake but the core of the method. What you trigger ends as a stem cell, and a stem cell in adult tissue is a teratoma. The question is not how to avoid the side effect but how to stop in time.
The time window
The answer is called partial reprogramming: only part of the way. In 2016, the group around Izpisua Belmonte published a cyclic scheme in Cell, 2 days on and 5 days off. In a mouse with premature aging, median lifespan rose from 18 to 24 weeks.
The same paper shows the counter-test: with 8 weeks of continuous operation, teratomas formed. The same intervention, only longer, and the result tips from benefit to tumor. The time window is not a detail; it is the method.
Three factors instead of four
In 2020, a paper in Nature from the group around David Sinclair left out c-Myc, the cancer gene among the four, and introduced only the remaining 3 factors into mouse retinal cells. After an injury, nerve fibers regrew and vision returned. Sinclair is co-founder and shareholder of the company behind it.
In 2022, a paper in Nature Aging extended this to normally aging animals: longer treatment, effects in kidney and skin, epigenetic clock running backward. The author list says almost as much as the result — Altos Labs and Genentech.
What the epigenetic clock measures
The best-known of these clocks comes from Steve Horvath: 353 sites in the genome, calibrated on 8000 samples. It predicts calendar age.
It does not say how much longer someone will live, and it is not a target to treat toward. Horvath’s paper contains the explanatory sentence: in stem cells, the clock reads almost zero. A value close to zero is therefore no proof of rejuvenation — a fully reprogrammed cell in the body would be a teratoma. “The clock ran backward” and “the animal is better off” are two statements; press releases usually contain only the first.
The first human study
Since March 2, 2026, the procedure has been tested in humans for the first time. Life Biosciences administers the agent ER-100, 3 factors, as an injection into the eye. The US authority had cleared the application at the end of January 2026, according to the company as the first reprogramming therapy ever. 18 people at 4 centers are taking part.
Safety and tolerability are measured. Not eyesight, not aging. The study is neither randomized nor blinded, and the monkey data behind it were presented at a conference, not peer-reviewed.
The gap to the money
Altos Labs launched in January 2022 with 3 billion dollars for basic research without a product, and Retro Biosciences is valued at 1.8 billion. Against this stands a phase 1 study without interim results. That does not make the science worse — the biology is in Nature, Science and Cell. It makes what is sold on top of it suspect.
What is well supported
The core is undisputed: four defined genes reset a differentiated cell to the stem cell state — demonstrated since 2006, recognized with the Nobel Prize in 2012. The cyclic principle in animals is also robust: 2 days on and 5 days off raised the median lifespan of a mouse with premature aging from 18 to 24 weeks, and in the retina, 3 factors without c-Myc were enough for regrowing nerve fibers and returning vision. The downside is equally well supported: the tumor risk, shown repeatedly and independently.
What the studies show
Yamanaka 2006, Nature 2013 and Cell 2014 — factors and the tumor problem
In 2006, Yamanaka showed that Oct-4, Sox-2, Klf-4 and c-Myc turn a skin cell back into a stem cell; Nobel Prize 2012. If these factors are briefly switched on in the living animal, teratomas form in the stomach, intestine and kidney. The 2014 paper, with Yamanaka among the authors, shows: even an interrupted pulse is enough for tumors, via methylation rather than mutation.
Izpisua Belmonte et al., Cell 2016 — the cyclic scheme
Cyclic scheme, 2 days on and 5 days off. In a mouse with premature aging, median lifespan rose from 18 to 24 weeks. With 8 weeks of continuous operation, teratomas formed — the same intervention, only longer.
Sinclair et al., Nature 2020 — the retina
c-Myc left out, only 3 factors in mouse retinal cells. After an injury, nerve fibers regrew and vision returned. Sinclair is co-founder and shareholder of the company behind it.
Nature Aging 2022 — normally aging animals
Longer treatment in normally aging mice, effects in kidney and skin, epigenetic clock running backward. Authors from Altos Labs and Genentech.
Life Biosciences 2026 — ER-100, first human study
Start on March 2, 2026, after clearance by the US authority at the end of January 2026. 3 factors as an injection into the eye, 18 participants at 4 centers, not randomized, not blinded. Endpoints are safety and tolerability, not eyesight and not aging. The underlying monkey data were presented at a conference and not published in peer-reviewed form.
Where the data stop
Nothing has yet been shown in humans. There is one ongoing study with 18 participants, without randomization and without blinding, and it is not designed to measure efficacy. What is reported about it relies on animal data, some of which are not peer-reviewed. Anyone who talks about rejuvenation in humans today is talking about the mouse.
Status, approval and legal
No reprogramming therapy is approved in Germany, the EU or the US. There is no product, no legal way to obtain it and nothing a doctor could prescribe. The only regular access is the ongoing safety study with ER-100 at 4 centers with 18 participants. As a gene therapy, the procedure would fall in Germany under medicines law and the European rules for advanced therapies; use outside an approved study is not provided for.
Safety
Here the main problem is not the lack of data but what the existing data show. The tumor risk has been demonstrated repeatedly and independently: teratomas with brief activation in the living animal, tumors after an interrupted pulse, teratomas with 8 weeks of continuous operation. It is not a rare side effect but the built-in endpoint of the very reaction one wants to use. That is why the first human study begins in the eye, a self-contained organ in which you can see early whether something is growing that should not grow. Tolerability data in humans are not available because the study is still running.
BK-Score Not studied in humans
| Human evidence | 1 | |
|---|---|---|
| Mechanism | 5 | |
| Safety data | 1 | |
| Hype gap | 3 | |
| Track record of use | 1 |
evidence 1: not a single result is available in humans — the first study has been running since March 2, 2026, with 18 participants at 4 centers, is not randomized and not blinded, and measures safety instead of effect. mechanism 5: the pathway is cleanly described in cell culture and animals, from 2 days on and 5 days off with 18 to 24 weeks of lifespan to the retinal work with 3 factors, but no step of the chain has been confirmed in humans. safety 1: there are no tolerability data in humans, and the monkey data behind ER-100 were only presented at a conference; in animals, by contrast, the tumor risk is clearly demonstrated, up to teratomas after 8 weeks of continuous operation. hype 3: the biology is real and published in Nature, Science and Cell, but press releases declare the backward-running epigenetic clock to be rejuvenation, although it reads almost zero in stem cells — and 3 billion dollars for Altos Labs as well as a valuation of 1.8 billion for Retro Biosciences stand against a phase 1 study without interim results. use 1: outside this one study, no human has received the procedure, and there is nothing to buy.
The score rates the state of knowledge, not the substance. “Safety data 9” means well studied – not harmless.
Subjective assessment by Biohacking Kompakt based on published scoring rules – not a scientific rating and not a medical recommendation. Rules and all ratings (German)
Frequently asked questions about partial reprogramming (Yamanaka factors)
What distinguishes partial from full reprogramming?
In full reprogramming, a cell is reset all the way to the stem cell state and loses its identity. In partial reprogramming, the same factors are switched on only briefly and switched off again before that happens. In the animal experiment this meant 2 days on and 5 days off. With 8 weeks of continuous operation, teratomas formed instead.
Can you get this today?
No. There is no approved product anywhere in the world and no legal way to obtain it. The only regular access is the ongoing study with ER-100 at 4 centers. Anything offered commercially under this name lies outside any approval.
Why is the study being done in the eye?
Because the eye is a self-contained organ that can be looked at directly. With a procedure whose best-known risk is uncontrolled growth, it is possible there to detect early whether something is growing that should not grow. The preliminary work for this comes from mouse retinal cells.
What does it mean when the epigenetic clock runs backward?
At first only that a pattern at 353 sites in the genome has changed. Steve Horvath’s clock was calibrated on 8000 samples to calendar age, not to remaining lifespan. In stem cells it reads almost zero, and a fully reprogrammed cell in the body would be a teratoma. A low value is therefore not proof of rejuvenation.
How high is the cancer risk?
In humans it has not been quantified, because no one has yet been treated outside the ongoing study. In animals it is clear: teratomas formed with brief activation in the living animal, with continuous operation over 8 weeks and even after an interrupted pulse. The risk is part of the principle of action; it is not a rare side effect.
Why is so much money flowing into a field without results?
The underlying biology is strong and comes from Nature, Science and Cell, not from advertising. Altos Labs launched in January 2022 with 3 billion dollars, and Retro Biosciences is valued at 1.8 billion. Against this stands a single phase 1 study with 18 participants and no interim results. The gap between the evidence and the capital is particularly large in this field.
Related
- Related topicKlotho
- Same section5-Amino-1MQ
- Same sectionFOXO4-DRI
- Same sectionStenabolic (SR9009)
- Same sectionMOTS-c
- Same sectionPE-22-28
Sources
- Takahashi & Yamanaka, Cell 2006 — reprogramming with four factors
- Abad et al., Nature 2013 — teratomas after factor activation in animals
- Ohnishi et al., Cell 2014 (with Yamanaka) — tumors after an interrupted pulse
- Ocampo et al. (Izpisua Belmonte), Cell 2016 — partial reprogramming
- Lu et al. (Sinclair), Nature 2020 — retina and vision
- Browder et al., Nature Aging 2022 — normally aging animals, Altos Labs and Genentech
- Horvath, Genome Biology 2013 — epigenetic clock based on 353 sites
- Life Biosciences 2026 — ER-100, first human study (registry entry)
Open in the database – with search, filters and comparison (German app)
Information only, not medical advice and not a usage or dosage recommendation. Prescription-only and unapproved substances belong in the hands of a physician. Last updated: 2026-09-19.