What is rapamycin? One molecule with five different jobs

A percentage gain only means something if the control mice lived a normal span. Matt Kaeberlein puts quality mouse controls at around 900 days, so a study whose untreated animals died early can make a modest drug effect look large.

By origin, yes. It was isolated from a soil bacterium and first characterized as an antifungal agent. Its immunosuppressive properties were discovered afterwards and turned out to be commercially far more important, which is why nobody uses it as an antifungal today.

Identical molecule, two names: rapamycin is the original research name, taken from Rapa Nui, and sirolimus is the international nonproprietary name it received on approval, sold first as Rapamune. Everolimus and temsirolimus are different molecules, chemically modified relatives known as rapalogs.

No, and they are not close: metformin is a cheap diabetes drug that works largely through AMPK and mitochondrial signaling. Rapamycin is an immunosuppressant that inhibits mTORC1 directly. Rapamycin extends lifespan reliably in mice, metformin does not, and metformin has decades of human safety data that rapamycin lacks at longevity doses.

No. It is produced by a soil bacterium, not by any plant or food, and there is no dietary source. Anything sold as a natural rapamycin is a different compound entirely, usually spermidine or a polyphenol, marketed on a mechanistic resemblance rather than an equivalence.

Yes: the Interventions Testing Program ran the study at three sites, and mice fed rapamycin from 600 days lived 14% longer if female and 9% longer if male at 90% mortality (per Harrison et al. 2009). The limitation is the mouse strain: genetically mixed UM-HET3 mice, not people.

It binds an intracellular protein called FKBP12, and the resulting complex inhibits mTORC1, the cell's main nutrient and growth sensor. Growth and protein synthesis slow, autophagy increases. The second complex, mTORC2, is much less sensitive to short exposures, which is the biological reason intermittent dosing exists.

People do, off-label and by prescription. What supports it is the animal data: it extends lifespan in every model tested, including mice started late in life. What does not yet exist is any human trial showing a lifespan or healthspan benefit, or any validated dose.

Because mTORC2, which governs insulin signaling among other things, is far less sensitive to brief exposure than mTORC1 (per Saxton and Sabatini, 2017). Intermittent exposure is meant to inhibit the first complex and leave the second largely alone. That is a mechanistic rationale, not an outcome tested in healthy people.

There is no controlled human trial showing that. Hair color changes appear in animal work and in anecdotal reports from people taking it, which is the weakest evidence category available.

From Streptomyces hygroscopicus, a bacterium in a soil sample collected on Easter Island in the 1960s. The island's Polynesian name, Rapa Nui, gave the compound its name.

Yes, for transplant rejection prevention, for lymphangioleiomyomatosis and in stent coatings. It is not approved for aging, longevity or healthspan, and prescribing it for those purposes is off-label use of an approved drug rather than use of an unapproved one.

Only roughly. Feeding in the 2009 Harrison study began at 600 days, about a 60-year-old in human terms, and that conversion is approximate, so the result speaks to a late-life start rather than a precise human age.

Mechanistic target of rapamycin, formerly mammalian target of rapamycin. The pathway is named after the drug because the drug was the tool that led researchers to it, not the other way around.