A brief pulse of rapamycin before the onset of aging extended lifespan by triggering lasting increases in autophagy. The authors called this phenomenon "rapamycin memory." Elevated autophagy was accompanied by increased levels of LManV and lysozyme in fruit flies, in intestinal enterocytes in female fly models, and its Man2B1 homologue in mice. In mice, a 3-month treatment in early adulthood had the same effect as chronic treatment, even 6 months after rapamycin was withdrawn. In the study published in the Aug. 29, 2022, issue of Nature Aging and led by researchers at the Max Planck Institute, scientists showed that the lifespan-increasing response to rapamycin treatment decreased with the age at which treatment is started.

The U.S. NIH’s National Institute on Aging’s Intervention Testing Program has been searching for ways to extend lifespan for more than two decades by now. And in its animal studies, it has been successful multiple times. There are half a dozen drugs, and a few lifestyle interventions, that reliably extend lifespan in one or both sexes by up to 30%. Read more in part four and five of BioWorld’s multipart series on extending the human lifespan.

The mammalian target of rapamycin (mTOR) inhibitor rapamycin extended the lifespan of female but not male flies, through sex-specific effects on the enterocytes that line the gut.