Brief exposure to rapamycin has the same anti-aging effects as lifelong treatment.
Imagine being able to take a medicine that prevents the decline that comes with age and keeps you healthy. Scientists are looking for drugs that have these effects. The most promising anti-aging drug currently is rapamycin. It is known for its positive effects on lifespan and health in experimental studies on laboratory animals. It is often given for life to get the maximum benefit from the drug. However, even at the low doses used in the prevention of age-related decline, negative side effects may occur. Additionally, 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 just shown in laboratory animals that brief exposure to rapamycin has the same positive effects as lifelong treatment. This opens new doors for potential application in humans.
Researchers 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 ailments of old age. Repurposing existing drugs for “geroprotection” provides an additional weapon in preventing age-related decline.
Currently, the most promising anti-aging drug is rapamycin, a cell growth inhibitor and immunosuppressant that is normally used in cancer treatment and after organ transplants. “At doses used clinically, rapamycin may have undesirable side effects, but for use of the drug in the prevention of age-related decline, these should be absent or minimal. Therefore, we wanted to know when and how long we needed to administer rapamycin to achieve the same effects as a lifelong treatment,” says Dr. Paula Juricic. She is the principal investigator of the study in the department of Professor Linda Partridge, director of the Max Planck Institute for the Biology of Aging.
Only a brief exposure
Scientists tested different time windows for short-term drug delivery in fruit flies. They found that a brief 2-week window of rapamycin treatment in young adult flies protected them against age-related gut pathologies and prolonged their life. A correspondingly short time window of 3 months of treatment beginning at 3 months of age in young adult mice had similar beneficial effects on gut health when they were middle-aged.
“These brief drug treatments in early adulthood produced equally strong protection as continuous treatment started at the same time. We also found that rapamycin treatment had the strongest and best effects when was administered early in life relative to middle age. When flies were treated with rapamycin late in life, on the other hand, it had no effect. Thus, rapamycin memory is activated mainly in early adulthood,” explains co-author Dr. Thomas Leech.
One step closer to applications
“We have found a way to circumvent the need for long-term chronic intake of rapamycin, so it might be more practical to apply it in humans,” says Dr. Yu-Xuan Lu, also a co-author of the paper. ‘article.
Professor Linda Partridge, the lead author of the study, comments: “It will be important to find out whether it is possible to achieve the geroprotective effects of rapamycin in mice and humans with treatment starting later. in life, because ideally the treatment period should be minimized. It may also be possible to use intermittent dosing. This study opened new doors, but also raised many new questions.
Reference: “Long-lasting geroprotection against brief rapamycin treatment in early adulthood through persistently increased intestinal autophagy” by Paula Juricic, Yu-Xuan Lu, Thomas Leech, Lisa F. Drews, Jonathan Paulitz , Jiongming Lu, Tobias Nespital, Sina Azami, Jennifer C. Regan, Emilie Funk, Jenny Fröhlich, Sebastian Grönke and Linda Partridge, August 29, 2022, natural aging.
The research for this study was conducted at the Max Planck Institute for the Biology of Aging and was funded by the CECAD Excellence Group for Aging Research.