The tree · branch 4 of 8
Broken proteins and waste
Misfolded proteins, the failure of the cell's recycling of its own worn parts, and the waste and cross-links between proteins that build up inside and between cells.
Of the twelve published hallmarks of ageing, this branch groups 2: misfolded proteins and failed protein quality control and the cell's recycling of its own worn parts failing.
Where this branch stands
required: the year cannot arrive until this branch is handled; handled when 2 treatments are in the clinic- 2023handled, in the middle run
- 2of 5 in the clinic already
- in clinical usefurthest stage reached
This branch already counts as handled: 2 of its treatments are in the clinic, the second of them since 2023, so every run of the model reads that year for it and the branch cannot be what holds the year back. Across all the runs, the middle year this branch is handled is 2023.
Two of this branch's leaves were already in the clinic when the leaves were written on 2026-10-16 (an antibody that clears amyloid from the brain, approved 2023; a drug that stops one misfolded protein settling in the heart, approved 2019), so with handled_when at two the branch counts as handled in 2023. Each treats one protein in one organ, which is less than the line above asks; the yearly review may raise handled_when for this branch or narrow what counts.
5 treatments and tools
listed by how soon each could reach its next rung- A drug stops a misfolded protein piling up in the heart and extends life
Next rung within 1 to 5 years. Transthyretin is a blood protein that, in many people over seventy, starts to misfold and settle in the heart muscle as a stiff waste, until the heart fails.
- An antibody clears amyloid from the brain and slows the decline of Alzheimer's disease
Next rung within 5 to 20 years. Amyloid is a protein that misfolds and piles up between brain cells with age, and in Alzheimer's disease it piles up faster.
- A drug that boosts the cell's recycling of its worn parts improves an age-related function in people
Next rung within 5 to 20 years. Cells break down and recycle their own worn parts, a process called autophagy, and it slows with age so that damaged proteins and worn power plants pile up inside the cell.
- A drug breaks the sugar cross-links that stiffen old tissue
Next rung more than 20 years away, if ever. Sugar in the blood slowly reacts with long-lived proteins such as the collagen in artery walls and skin, welding them together with cross-links that the body cannot undo; arteries stiffen, blood pressure rises, and the heart works harder.
- Eye drops dissolve the clouded protein of a cataract
Next rung more than 20 years away, if ever. A cataract is the clearest everyday case of a broken protein: the crystallins that keep the lens of the eye transparent misfold and clump with age until the lens goes cloudy, and the only treatment is to cut the lens out and put in a plastic one.
What would move this
the next test each treatment needs, and the branch's own lineA drug that clears a kind of waste throughout the body, not one organ, with a healthy-years or function result in a controlled trial in people.
- A drug stops a misfolded protein piling up in the heart and extends life Next rung: in wide use. Available to the general public in at least one country without joining a trial, and taken up by many people. Settled by the peer-reviewed trial report; the regulator's approval record; published uptake figures for the wide-use rung.
- An antibody clears amyloid from the brain and slows the decline of Alzheimer's disease Next rung: in wide use. Available to the general public in at least one country without joining a trial, and taken up by many people. Settled by peer-reviewed trial reports; the regulator's approval record; published uptake figures for the wide-use rung.
- A drug that boosts the cell's recycling of its worn parts improves an age-related function in people Next rung: first human. At least one person has had it, with a public record of that result. Settled by the peer-reviewed trial report; the regulator's approval record for the clinic rung.
- A drug breaks the sugar cross-links that stiffen old tissue 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 peer-reviewed reports; the regulator's approval record for the clinic rung.
- Eye drops dissolve the clouded protein of a cataract Next rung: first human. At least one person has had it, with a public record of that result. Settled by peer-reviewed reports, with a replication; the regulator's approval record for the clinic rung.
Its history
the handled year, computation by computationThe year was first computed on 17 October 2026, with this branch handled in the middle run by 2023. 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 branchPromised, in public
- 5 April 2022Retro Biosciences: A first human trial of a drug that boosts the cell's recycling of its own worn parts (autophagy) by about 2023-04.
On the record
- 9 February 2026A Multicenter, Randomized, Double-Masked, Placebo-Controlled Pilot Study to Evaluate the Efficacy and Safety of ZOC2017217 in Subjects With Age-Related Cataract
- 13 July 2026FDA Approves LEQEMBI IQLIK (lecanemab-irmb) Subcutaneous Injection as an Initiation Dose for Early Alzheimer's Disease
- 7 October 2024Implausibility of radical life extension in humans in the twenty-first century
- 3 January 2023Hallmarks of aging: An expanding universe
- 6 June 2013The Hallmarks of Aging
- 12 May 2022Foreword to the Aubrey de Grey and Charles Brenner debate (Let's Talk Longevity newsletter)
- 15 June 2004Escape Velocity: Why the Prospect of Extreme Human Life Extension Matters Now