The tree · Broken proteins and waste
A drug that boosts the cell's recycling of its worn parts improves an age-related function in people
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. Several substances turn it back up. Spermidine, found in wheat germ and aged cheese, lengthened the lives of old mice and protected their hearts in a 2016 report from Graz and elsewhere. In people the record is thinner: a 2022 controlled trial of spermidine in older adults found no effect on memory, and the best-known recycling booster, rapamycin, has its own leaves on the energy branch. The leaf asks for a human function result, not a blood marker.
What would count
A controlled trial in people reports that a drug or supplement given to boost autophagy (the cell's recycling of its worn parts) improves an age-related function (memory, heart function, muscle strength) more than placebo on the trial's pre-stated main measure, in a peer-reviewed report. The animal rung is the same in a living animal, or a longer life. For the clinic rung: a regulator approves such a treatment for an age-related condition.
Who settles it: The peer-reviewed trial report; the regulator's approval record for the clinic rung.
Where it stands
Shown in animals. Reached 14 November 2016, on the record of doi.org. Next rung within 5 to 20 years.
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 2045, no earlier than 2033 and no later than 2095; 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 | |
|---|---|---|---|---|
| First human | 2028 | 2032 | 2050 | |
| In clinical use | 2033 | 2045 | 2095 | feeds the year at the top |
Why. Spermidine and related supplements are cheap and widely sold, which means trials are small and underfunded; the likely year assumes a mid-sized controlled trial reports a function benefit in the early 2030s and that an approval for an age-related condition, rather than supplement sales, comes in the mid 2040s. The earliest assumes a trial already running reports positive by 2029; the latest allows for the supplements staying unproven and the rung being reached by a prescription drug designed for the purpose much later.
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. What was seen falls short of the test: a 2026-07 meta-analysis of urolithin A trials in Frontiers in Nutrition (a pooling of older trials, not a new controlled trial, and dated before the window); a registered six-month trial of urolithin A against placebo in middle-aged adults (ClinicalTrials.gov NCT07231783) still recruiting with no result; a 40-person pilot of spermidine on vaccine response in people over 65, which is an immune marker and not an age-related function on a pre-stated main measure; and worm and cell work on new autophagy activators (a bioRxiv preprint of 2026-01). The POLYCAD trial of spermidine in heart disease was described as not yet reported. No regulator's record and no peer-reviewed controlled human trial with a function main measure appeared in the window.source 1, source 2
What the story so far says about it
Promised, 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.
Notes
The difficulty with this leaf is that most drugs on the energy branch also boost recycling, so a human result there could be claimed here; the test asks that the drug be given for that purpose and the report say so. Rapamycin's human results are on the energy branch and are not counted twice.
Not yet verified
These facts in the record were written from memory or from a secondary source and have not yet been checked against the paper, the regulator's record or the registry. Nothing here is presented as settled until it is cleared, by checking it and either deleting the line or correcting the record.
- That trehalose, urolithin A and metformin are described as autophagy boosters holds (urolithin A as a mitophagy activator). Two controlled trials of urolithin A (2022) missed their main measures but improved muscle endurance or strength on secondary measures; the leaf's test asks for the main measure, so they are not counted.