Short exposure to rapamycin has the same antiaging effects as lifelong treatment.
Imagine being able to take a drug that prevents the decline that comes with age and keeps you healthy. Scientists are looking for drugs that have these effects. Currently, the most promising anti-aging drug is Rapamycin. It is known for its positive effect on life and health in experimental studies with laboratory animals. It is often given throughout life to get the maximum beneficial effects of the drug. However, even at the low doses used to prevent age-related decline, negative side effects can occur. Also, it is always desirable to use the lowest effective dose. A research group at the Max Planck Institute for the Biology of Aging in Cologne, Germany, has now shown in laboratory animals that short exposure to rapamycin has the same positive effects as lifelong treatment. This opens new doors for potential application in humans.
Scientists are increasingly focusing on combating the negative effects of aging. Lifestyle changes can improve the health of older people, but they alone are not enough to prevent the diseases of old age. Repurposing existing drugs for “geroprotection” provides an additional weapon to prevent age-related decline.
Currently, the most promising anti-aging drug is rapamycin, a cell growth inhibitor and immunosuppressant commonly used in cancer treatment and after organ transplants. “At doses used clinically, rapamycin can have unwanted side effects, but for the drug’s use in preventing age-related decline, these should be absent or minimal.” So we wanted to understand when and for how long we should give rapamycin to achieve the same effects as lifelong treatment,” explains Dr. Paula Juricic. She is the lead researcher of the study in the department of Prof. Linda Partridge, director of the Max Planck Institute for the Biology of Aging.
Just a brief exposure
The scientists tested different time windows of short-term application of the drug to fruit flies. They found that a short window of 2 weeks of rapamycin treatment in young adult flies protected them from age-related gut pathology and extended their lifespan. A correspondingly short time window of 3 months of treatment starting at 3 months of age in young, adult mice had similar beneficial effects on gut health as when they were middle-aged.
“These short drug treatments in early adulthood provide as strong a protection as continuous treatment started at the same time.” We also found that rapamycin treatment had the strongest and best effects when it was given at an early age compared to middle age. On the other hand, when flies were treated with rapamycin at a later age, there was no effect. So the rapamycin memory is primarily activated in early adulthood,” explains Dr. Thomas Leach, co-author of the paper.
One step closer to applications
“We found a way to bypass the need for chronic, long-term administration of rapamycin, so it may be more practical to administer it in humans,” said Dr. Yu-Xuan Lu, also a co-author of the paper.
Professor Linda Partridge, senior author of the study, commented: “It will be important to find out whether it is possible to achieve the geroprotective effects of rapamycin in mice and in humans by starting treatment later in life, as ideally the period of treatment should be kept to a minimum. It is also possible to use intermittent dosing. This study opened new doors, but also raised many new questions.
Reference: “Long-lasting geroprotection from brief rapamycin treatment in early adulthood through persistently increased intestinal autophagy” by Paula Juricic, Yu-Xuan Lu, Thomas Leach, Lisa F. Drews, Jonathan Paulitz, Jiongming Lu, Tobias Nespital, Sina Azami, Jennifer C. Regan, Emilie Funk, Jenny Fröhlich, Sebastian Grönke and Linda Partridge, 29 Aug 2022, Aging of nature.
The research for this study was conducted at the Max Planck Institute for the Biology of Aging and was funded by the CECAD Cluster of Excellence for Aging Research.