Brief exposure to rapamycin has the same anti-aging effects as permanent treatment.
Imagine being able to take a medicine that prevents age-related decline and keeps you healthy. Scientists are looking for drugs that have these effects. The most promising current anti-aging drug is rapamycin. It is known for its positive effects on life and health in experimental studies with laboratory animals. It is often administered throughout life to achieve the maximum beneficial effects of the drug. However, even at the low doses used in the prevention of age-related decline, negative side effects can occur. Furthermore, it is always desirable to use the lowest effective dose. A research team from the Max Planck Institute for Biology of Aging in Cologne, Germany, has now shown in laboratory animals that brief exposure to rapamycin has the same positive effects as permanent treatment. This opens up new doors for potential application in humans.
Researchers are increasingly focused on combating the negative effects of aging. Lifestyle changes can improve the health of older people, but these alone are not enough to prevent the ills of old age. The reuse of existing ‘geroprotection’ drugs is providing an additional weapon in the prevention of age-related decline.
Currently, the most promising anti-aging drug is rapamycin, a cell growth inhibitor and immunosuppressant commonly used in cancer therapy and after organ transplants. “At the dosages used clinically, rapamycin can have unwanted side effects, but for the drug to be used in the prevention of age-related decline, these must be absent or minimal. Therefore, we wanted to find out when and for how long we need to administer rapamycin to achieve the same effects as permanent treatment, “explains Dr Paula Juricic. She is the study’s principal investigator in the department of Prof. Linda Partridge, director of the Max Planck Institute for Biology of Aging.
Short exposure only
Scientists tested different time windows of short-term drug delivery in fruit flies. They found that a short 2-week window of rapamycin treatment in young and adult flies protected them from age-related disease in the gut and prolonged their life. A corresponding short time window of 3 months of treatment initiated at 3 months of age in young adult mice had similar beneficial effects on gut health when they were middle-aged.
“These short drug treatments in early adulthood produced just as strong protection as continued treatment started at the same time. We also found that rapamycin treatment had the strongest and best effects when given in early childhood versus middle age. When the flies were treated with rapamycin at an older age, however, it had no effect. Hence, rapamycin memory is mainly activated in early adulthood, ”explains Dr Thomas Leech, co-author of the article.
One step closer to applications
“We have found a way around the need for chronic long-term rapamycin intake, so it may be more practical to apply it in humans,” says Dr. Yu-Xuan Lu, also co-author of the article.
Professor Linda Partridge, senior author of the study, comments: “It will be important to find out whether the geroprotective effects of rapamycin can be achieved in mice and humans with treatment starting later in life, as ideally the treatment period should be minimized. It may also be possible to use intermittent dosing. This study has opened new doors, but it has also raised many new questions ”.
Reference: “Long-lasting geroprotection from short rapamycin treatment in early adulthood from 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, 29 August 2022, Aging of nature.
DOI: 10.1038 / s43587-022-00278-w
The research for this study was conducted at the Max Planck Institute for Biology of Aging and was funded by the CECAD Cluster of Excellence for Aging Research.