The tree · Broken proteins and waste
A drug breaks the sugar cross-links that stiffen old tissue
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. A drug that broke those welds was tried in people in 2001: alagebrium made the arteries of older adults measurably more elastic over eight weeks in a small controlled trial. A placebo-controlled trial in 102 people with heart failure (2011) found no gain, the company ran out of money and ended its remaining trials in January 2009, and nothing shows the drug breaks glucosepane, the main human cross-link. A new generation of drugs aimed at glucosepane was in the laboratory when this was written.
What would count
A person given a drug meant to break advanced glycation cross-links afterwards has measurably more elastic arteries, or less of the cross-link in a tissue sample, in a peer-reviewed controlled report. The animal rung is the same in a living animal. For the clinic rung: a regulator approves such a drug for an age-related condition.
Who settles it: Peer-reviewed reports; the regulator's approval record for the clinic rung.
Where it stands
First human. Reached 25 September 2001, on the record of doi.org. Next rung more than 20 years away, if ever.
When it reaches the clinic: the project's estimate
This is the one thing on this page that is a judgment rather than a record. The project's estimate of the year it reaches the clinic is 2050, no earlier than 2036 and no later than not this century; the model draws from that range every run, with the likely year the most probable draw. Set 16 October 2026, a first pass awaiting an outside review.
| Rung | No earlier than | Most likely | No later than | |
|---|---|---|---|---|
| In clinical use | 2036 | 2050 | not this century | feeds the year at the top |
Why. The class has one human result from 2001 and nothing since, and the current candidates had not reached animals in a peer-reviewed report. The likely year assumes the glucosepane breakers show an animal result by 2030 and reach an approval for an arterial condition around 2050; the earliest assumes a faster path through a skin or kidney indication; the latest allows for the chemistry never yielding a safe drug.
Changes to this record
None since it was written on 16 October 2026. Every change to the stage or the estimate lands here with its date, the old value, the new one and the reason, and a change to the estimate never happens because a number looked wrong: it needs a dated reason and a source.
The last readings
- 17 October 2026 Quiet
Nothing in the window. All three searches returned only background older than 2026: the 1998 rat record and 2001 human record already on the leaf, the 2014 note that alagebrium had no effect in later human trials, and advocacy-site profiles of Revel Pharmaceuticals (a spin-out of the Spiegel laboratory at Yale developing enzymes that cut glucosepane) with no trial registration, no peer-reviewed animal report and no company release dated 2026. One undated advocacy page says the company has had difficulty reproducing the original glucosepane-cleaving finding and has instead found an enzyme that removes a different sugar adduct (carboxymethyl-lysine); it is not a record of the settler's kind and is not dated, so it is noted here only as a lead for a later reading.
What the story so far says about it
No promise, self-experiment or logged paper names this one yet.
Notes
Cross-links are not one of the twelve published kinds of ageing damage (the "hallmarks"), and the branch carries them in its meaning rather than its hallmark list; they are on the tree because arterial stiffening is among the most reliable changes of age and nothing in the clinic reverses it. The 2001 result stands as a first human on a measurement for the class even though the drug that produced it is gone.