The tree · Energy and fuel sensing
A rapamycin-type drug improves an age-related measure in older people
Rapamycin and its relatives damp down a pathway (mTOR) that senses how much food is coming in, and they are the drugs with the strongest record of extending life in animals. The question for people is whether a dose low enough to be safe does anything measurable. In 2014 a Novartis team gave a relative of rapamycin, everolimus, to 218 people over sixty-five for six weeks and found that their response to the flu vaccine improved by about a fifth compared with placebo, the first controlled sign that the drug touches ageing in people. A larger late-stage trial of a successor drug, aimed at winter infections, failed in 2019; and a crowd-funded year-long trial of low-dose rapamycin in 114 adults, published in 2025, found no change on its main measure, body fat, with small gains in lean mass and well-being in some groups.
What would count
A controlled trial in people reports that a drug acting on the mTOR pathway, at a dose given for ageing rather than for transplant or cancer, improves an age-related measure (immune response, muscle, a validated clock, a function) more than placebo on the trial's pre-stated main measure, in a peer-reviewed report. For the clinic rung: a regulator approves such a drug for an age-related condition in otherwise healthy older people, or a named clinical setting prescribes it for that purpose in routine care and publishes that practice.
Who settles it: The peer-reviewed trial report; the regulator's approval record, or a named clinical setting's published practice, for the clinic rung.
Where it stands
First human. Reached 24 December 2014, on the record of Mannick and 11 others, 24 December 2014 (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 2039, no earlier than 2031 and no later than 2080; 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 | 2031 | 2039 | 2080 | feeds the year at the top |
Why. The 2019 failure cost the field its one company sponsor; the trials now running are academic and small. The likely year assumes a mid-sized controlled trial (in the immune system, muscle or the gums, where several are running) reports positive in the early 2030s and a regulator or a named clinic adopts the drug for that purpose later in the decade; the earliest allows that a clinic publishes its practice soon after a positive trial; the latest allows for the drug staying off-label for good.
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: no peer-reviewed controlled trial of an mTOR drug at an ageing dose in older people, and no regulator's approval or published clinic practice, dated 2026-10-10 to 2026-10-17 was found. The searches returned the 2025 PEARL trial the record already holds, three registered trials with no results (RESTOR, NCT06658093, a dose-finding study of rapamycin and everolimus in people aged 65 to 90 at San Antonio, described on radio on 2026-05-31; the Everolimus Aging Study, NCT05835999, daily against weekly against placebo; and the Wisconsin RAP PAC phase 1 study, NCT05949658, still enrolling), and an undated preprint reporting lower p21 in immune cells of older adults on rapamycin against placebo, which is not peer-reviewed.source 1, source 2, source 3, source 4
What the story so far says about it
On the record
- 24 December 2014mTOR inhibition improves immune function in the elderly
- 4 April 2025Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results
Notes
Doctors at a number of private clinics prescribe rapamycin off-label for ageing, and many people take it; the test asks for a regulator's approval or a published routine practice on the strength of a controlled trial, and neither exists. The 2014 trial is the one positive controlled result and it is twelve years old. A separate leaf, a drug makes people live longer in good health, holds the lifespan question; this one holds the measurable short-term effect.
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.
- No animal rung is recorded on this leaf: the 2009 mouse lifespan result (Harrison and colleagues, Nature, 2009-07-08) is on the companion leaf and shows longer life, not the improvement of an age-related function that this leaf asks for; whether it should also be recorded here is undecided.