The tree · branch 3 of 8

The cell's settings

The chemical marks that tell a cell which of its genes to read, which drift with age so that cells slowly forget what they are. Resetting them part of the way has reversed signs of age in animals.

Of the twelve published hallmarks of ageing, this branch groups one: drift in the marks that say which genes a cell reads.

Where this branch stands

required: the year cannot arrive until this branch is handled; handled when 2 treatments are in the clinic

2044handled, in the middle run
0of 5 in the clinic already
first humanfurthest stage reached

Nothing under this branch is in the clinic yet. In each run of the model a year is drawn for every treatment from its range, and the branch counts as handled when the second of those years arrives. Across all the runs, the middle year this branch is handled is 2044.

5 treatments and tools

listed by how soon each could reach its next rung

The chemical marks on one gene are rewritten in a person, with no cut in the DNA Shown in animals clinic likely 2036, 2031 to 2070
Next rung within 1 to 5 years. Wholesale resetting of a cell's settings is one route; the other is to rewrite the marks on a single chosen gene, switching it off or on for good without cutting the DNA.
A person receives cell-resetting genes in a registered trial First human clinic likely 2040, 2033 to 2075
Next rung within 5 to 20 years. The genes that can partially reset a cell's age had been tried only in animals until 2026.
A person's biological age, read from the marks on their DNA, falls after a treatment First human clinic likely 2042, 2032 to 2085
Next rung within 5 to 20 years. The chemical marks that tell a cell which genes to read drift with age in a regular enough way that a reading of them from a blood sample gives a "biological age".
Partially resetting cells reverses ageing in a living animal Shown in animals clinic likely 2041, 2033 to 2075
Next rung within 5 to 20 years. Every cell carries chemical marks that say which of its genes to read, and the marks drift with age so that cells slowly forget what they are.
A mix of small-molecule drugs resets a cell's age without gene therapy Idea only clinic likely 2050, 2038 to not this century
Next rung more than 20 years away, if ever. Resetting a cell's age with genes needs a virus to carry them and a way to switch them off, which is why the first human trial is in the eye, a small sealed organ.

What would move this

the next test each treatment needs, and the branch's own line

A measured reversal of a marker of biological age in a person after a brief, controlled dose of reprogramming genes, in a peer-reviewed report.

The chemical marks on one gene are rewritten in a person, with no cut in the DNA Next rung: first human. At least one person has had it, with a public record of that result. Settled by peer-reviewed reports or the trial registry's posted results; the regulator's approval record for the clinic rung.
A person receives cell-resetting genes in a registered trial Next rung: in clinical use. A regulator somewhere has approved it, or it is in routine use in a named clinical setting, so a doctor can give it to a patient outside a trial. Settled by the trial registry entry and the sponsor's dated notice of the dose for the first-human rung; the peer-reviewed report when it comes; the regulator's approval record for the clinic rung.
A person's biological age, read from the marks on their DNA, falls after a treatment Next rung: in clinical use. A regulator somewhere has approved it, or it is in routine use in a named clinical setting, so a doctor can give it to a patient outside a trial. Settled by the peer-reviewed report; the regulator's approval record, or a named clinical setting's published practice, for the clinic rung.
Partially resetting cells reverses ageing in a living animal Next rung: first human. At least one person has had it, with a public record of that result. Settled by peer-reviewed reports; the trial registry and report for the first person treated; the regulator's approval record for the clinic rung.
A mix of small-molecule drugs resets a cell's age without gene therapy Next rung: shown in animals. Shown to work in a living animal, in a peer-reviewed report. Settled by peer-reviewed reports; the trial registry and report for the first person treated; the regulator's approval record for the clinic rung.

Its history

the handled year, computation by computation

The year was first computed on 17 October 2026, with this branch handled in the middle run by 2044. Every estimate under it is still a first pass. From the second computation on, this section charts the branch's handled year run by run, so a reader who sees the year at the top move can tell which branch moved it.

What the story so far says about it

the promises, the self-experiments and the papers that bear on this branch

Promised, in public

2009Ray Kurzweil and Terry Grossman: By about 2029, the means to reprogram human biology and change genes so as to live decades longer than a long life now (their bridge two), with circulating nanorobots within the same two decades; bridge three, living indefinitely, undated beyond following in turn. Verdict: not yet due, due 2029.
15 December 2016Salk Institute (Juan Carlos Izpisua Belmonte's laboratory): A first human trial of a treatment based on partial reprogramming (resetting the chemical marks that tell a cell which genes to read) by 2026 at the latest, hedged as may and up to. Verdict: delivered.
10 September 2019David Sinclair: No date. The book's nearest commitments are hedged: that if a few of the most promising therapies come to fruition it is not an unreasonable expectation for anyone alive and healthy in 2019 to reach a hundred in good health, and that if reprogramming reaches its potential a hundred and fifty might be possible for someone alive now. Verdict: cannot be settled.
19 January 2022Altos Labs: No date and no named treatment: a mission statement, with three billion dollars fully committed. The only date in the release is its chief executive's start date. Verdict: cannot be settled.
26 September 2022Charles Brenner: No date or result: a critique holding that ageing is not a disease, that getting healthier is not age reversal, and that the book's claims of reversal in people are stories, not findings. Verdict: cannot be settled.
25 August 2023David Sinclair: A first human trial of his partial-reprogramming treatment for blindness (Life Biosciences' ER-100) under way by about 2025-08 at the latest, hedged as his prediction. Verdict: missed.
21 October 2024Life Biosciences: A first human trial of ER-100 started between 2025-07 and 2025-12. Verdict: missed.

On the record

8 October 2026Life Biosciences Announces First-in-Human Data from Ongoing Phase 1 Trial Evaluating ER-100 in Optic NeuropathiesInc..
7 October 2024Implausibility of radical life extension in humans in the twenty-first centuryOlshansky and 3 others.
15 December 2016In Vivo Amelioration of Age-Associated Hallmarks by Partial ReprogrammingOcampo and 21 others.
2 December 2020Reprogramming to recover youthful epigenetic information and restore visionLu and 28 others.
3 January 2023Hallmarks of aging: An expanding universeLópez-Otín and 4 others.
6 June 2013The Hallmarks of AgingLópez-Otín and 4 others.
9 June 2026Life Biosciences Announces First Patient Dosed in Phase 1 Trial of ER-100 for Optic NeuropathiesInc..
12 May 2022Foreword to the Aubrey de Grey and Charles Brenner debate (Let's Talk Longevity newsletter)Gobel.
8 September 2019Reversal of epigenetic aging and immunosenescent trends in humansFahy and 9 others.
15 June 2004Escape Velocity: Why the Prospect of Extreme Human Life Extension Matters NowGrey.

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