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    Partial reprogramming

    Also known as epigenetic reprogramming, in vivo reprogramming, cellular rejuvenation, OSK, OSKM

    Partial reprogramming briefly switches on some of the Yamanaka factors that turn adult cells into stem cells, aiming to restore youthful gene activity without erasing cell identity.[1][2] It reversed signs of aging in mice, and in 2026 the first therapy based on it, ER-100, entered a human safety trial in eye disease.[3][4]

    Editor reviewedStrict sourcingUpdated Aging and longevity biologyLife sciencesHealth and medicine
    Key facts

    From stem cells to rejuvenation

    In 2006 researchers showed that four factors, Oct3/4, Sox2, c-Myc and Klf4, could turn adult mouse cells into induced pluripotent stem (iPS) cells.[1] These reprogrammed cells read as nearly zero years old on the Horvath epigenetic clock.[5] That raised a question: could a brief dose of the factors make cells younger without turning them into stem cells?

    The danger is real. Transplanted iPS cells formed tumours in mice, and switching on all four factors inside living mice caused teratomas in multiple organs.[6][7]

    Evidence in animals

    In 2016, short, cyclic expression of the four factors (OSKM) improved hallmarks of aging and extended lifespan in a mouse model of premature aging. It also improved recovery from metabolic disease and muscle injury in older normal mice.[2][8] In 2020, a three-factor version without c-Myc (OSK) restored youthful DNA methylation in mouse retinal nerve cells, promoted nerve regrowth and reversed vision loss in a glaucoma model and in aged mice.[3] The effects required the DNA demethylases TET1 and TET2, which the authors interpreted as tissues retaining a record of youthful epigenetic information.[9]

    Later studies moved to normally aging animals. In 2022, longer-term partial reprogramming in wild-type mice rejuvenated tissues such as kidney and skin and reversed epigenetic clock readings, and longer regimens worked better than short ones.[10] In 2024, researchers at the company Rejuvenate Bio delivered an inducible OSK system throughout the body with an AAV gene therapy vector. In 124-week-old male mice it extended median remaining lifespan by 109% over controls and improved frailty scores.[11] That result comes from one company-run study in males only.[11]

    Work on mechanism continues. A 2025 Cell study described a “mesenchymal drift” in gene expression across many human tissues and diseases, and found that partial reprogramming reduced it before cells lost their identity.[12]

    First human trial

    In January 2026 the FDA cleared Life Biosciences’ IND for er-100, the first partial epigenetic reprogramming therapy cleared for human testing.[13] ER-100 delivers the three OSK factors to the eye. They are switched on by daily oral doxycycline for about eight weeks.[14][15] The first patient was dosed in June 2026 in a Phase 1 trial in glaucoma and NAION, two optic nerve diseases.[4] In October 2026 the company reported no serious adverse events in its first three patients.[16]

    Players and open questions

    altos-labs, launched in 2022 with US$3 billion, describes its mission as reversing disease through cell rejuvenation.[17][18] It has set up an Institute of Computation to model biological resilience.[19] Life Biosciences, the developer of ER-100, holds licences to patents on OSK and the switch used to turn it on.[20]

    AI-designed factors are a newer thread. Retro Biosciences worked with openai on GPT-4b micro, a model trained to suggest changes to protein sequences. In January 2025 OpenAI said its suggestions made two Yamanaka factors, SOX2 and KLF4, more than 50 times as effective on some preliminary measures. These are company claims that had not been peer reviewed when announced.[21] For the broader use of AI in molecule design, see how AI discovers molecules and materials. Key unknowns include long-term safety, given the tumour risk of full reprogramming, and whether local results in the eye can extend to whole-body aging.[7] Trials still target specific diseases, because the FDA does not recognize aging as a disease and no regulatory framework exists for approving aging-targeted therapies.[22]

    Questions readers ask

    What are Yamanaka factors?

    Four proteins, Oct3/4, Sox2, c-Myc and Klf4, that can turn adult mouse cells into induced pluripotent stem cells, shown in 2006.[1]

    Why not reprogram cells fully?

    Fully reprogrammed cells can form tumours. Switching on all four factors inside living mice caused teratomas in multiple organs.[6][7]

    Has partial reprogramming been tested in people?

    Yes, from 2026. Life Biosciences' ER-100 entered a Phase 1 safety trial in glaucoma and NAION, and its first three patients had no serious adverse events at the lowest dose.[4][16]

    Sources

    Each numbered claim is a statement we checked against the sources listed with it. Status shows how well established it is.

    1. [1]

      In 2006 researchers showed that adult mouse cells can be turned into induced pluripotent stem (iPS) cells by introducing four factors, Oct3/4, Sox2, c-Myc and Klf4. confirmedas of 2006-08-25

    2. [2]

      In 2016, short-term cyclic expression of the four Yamanaka factors (partial reprogramming) improved hallmarks of aging and extended lifespan in a mouse model of premature aging. confirmedas of 2016-12-15

    3. [3]

      In 2020, expressing three factors (Oct4, Sox2 and Klf4, or OSK) in mouse retinal ganglion cells restored youthful DNA methylation patterns, promoted nerve regeneration and reversed vision loss in a glaucoma model and in aged mice. confirmedas of 2020-12-02

    4. [4]

      On 9 June 2026 Life Biosciences announced the first patient dosed in its Phase 1 trial of ER-100 (NCT07290244) in open-angle glaucoma and non-arteritic anterior ischemic optic neuropathy (NAION), which evaluates safety and tolerability with additional visual-function endpoints. confirmedas of 2026-06-09

    5. [5]

      DNA methylation age measured by the Horvath clock is close to zero for embryonic stem cells and induced pluripotent stem cells. confirmedas of 2026-10-10

    6. [6]

      Transplanted iPS cells formed tumours containing tissues from all three germ layers in mice. confirmedas of 2006-08-25

    7. [7]

      Transient induction of the four Yamanaka factors inside living mice caused teratomas to emerge from multiple organs. confirmedas of 2013-09-11

    8. [8]

      The 2016 study also reported that in vivo OSKM expression improved recovery from metabolic disease and muscle injury in older normal mice. confirmedas of 2016-12-15

    9. [9]

      The vision and nerve-regeneration benefits of OSK reprogramming in mice required the DNA demethylases TET1 and TET2, suggesting cells retain a record of youthful epigenetic information. confirmedas of 2020-12-02

    10. [10]

      A 2022 study found that longer-term partial reprogramming in normally aging mice had rejuvenating effects in tissues such as kidney and skin, reversed epigenetic clock measures, and was more effective than short-term regimens. confirmedas of 2022-03-07

    11. [11]

      In a 2024 study by researchers at Rejuvenate Bio, systemically delivered AAV vectors carrying inducible OSK extended the median remaining lifespan of 124-week-old male mice by 109% over controls and improved frailty scores. confirmedas of 2024-02-01

    12. [12]

      A 2025 Cell study reported a pervasive "mesenchymal drift" in gene expression across human tissues and diseases and found that Yamanaka-factor partial reprogramming reduced it before cells lost their identity. confirmedas of 2025-08-14

    13. [13]

      On 28 January 2026 Life Biosciences announced FDA clearance of its investigational new drug (IND) application for ER-100 in optic neuropathies, the first partial epigenetic reprogramming therapy cleared for human testing. confirmedas of 2026-01-28

    14. [14]

      ER-100 is a gene therapy that uses controlled expression of three transcription factors, OCT4, SOX2 and KLF4 (OSK). confirmedas of 2026-06-09

    15. [15]

      ER-100's factors are switched on with the oral antibiotic doxycycline, taken daily for about eight weeks after a single injection into the eye. confirmedas of 2026-10-08

    16. [16]

      In first-in-human data released on 8 October 2026, three open-angle glaucoma participants given the lowest ER-100 dose had no dose-limiting toxicities or serious adverse events. confirmedas of 2026-10-08

    17. [17]

      Altos Labs launched on 19 January 2022 with US$3 billion in committed funding, initially based in the San Francisco Bay Area, San Diego and Cambridge, UK. confirmedas of 2022-01-19

    18. [18]

      Altos Labs says its mission is to reverse disease, injury and disability by restoring cell health and resilience through cell rejuvenation. confirmedas of 2026-10-10

    19. [19]

      Altos Labs formed an Institute of Computation to build computational models of biological resilience at the cell, organ and organism levels, alongside its Institutes of Science and Institute of Medicine. confirmedas of 2026-10-10

    20. [20]

      Patents on OSK and the rtTA4 switch used for inducible expression have been licensed to Life Biosciences, according to a 2024 paper's conflict-of-interest statement. confirmedas of 2024-02-01

    21. [21]

      In January 2025 OpenAI said a protein-engineering model, GPT-4b micro, built with the longevity company Retro Biosciences, suggested changes that made two Yamanaka factors more than 50 times as effective on some preliminary measures; outside scientists could not assess the claim until it was published. reportedas of 2025-01-17

    22. [22]

      Papers published in 2025 in peer-reviewed journals state that the FDA does not recognize aging as a disease and that no regulatory framework exists for developing or approving therapies that target aging, so such therapies are developed through disease-specific pipelines. confirmedas of 2025-08-04

    23. [23]

      The authors of the 2023 hallmarks review describe the twelve hallmarks as interconnected with one another. confirmedas of 2026-10-10

    Revision history (2)
    1. Page created.
    2. Refresh: added 2022 long-term reprogramming and 2024 whole-body OSK mouse studies, the OpenAI and Retro Biosciences work on AI-designed factors, and licensing background.

    Created Oct 10, 2026. Last reviewed by an editor on Oct 10, 2026. Next scheduled review: Jan 10, 2027.

    Cite this page

    "Partial reprogramming." ContentLora, updated Oct 10, 2026. https://contentlora.com/wiki/partial-reprogramming

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