Brief exposure to rapamycin has the same anti-aging effects as lifelong treatment

Summary: Brief exposure to rapamycin, a promising anti-aging drug that has positive effects on health and lifespan, has the same effect as long-term exposure to the drug in animal models. The results pave the way for testing the effects of short-term exposure to rapamycin on human lifespan.

Source: Max Planck Institute

Imagine being able to take a drug that prevents the decline that comes with age and keeps you healthy. Scientists are trying to find a drug that has these effects.

The most promising anti-aging drug right now is rapamycin, known for its positive effects on lifespan and health in experimental studies with lab animals.

To achieve the maximum beneficial effects of the drug, it is often given for life. However, even at the low doses used in the prevention of age-related decline, negative side effects can occur and 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 a lifelong treatment opening up new gates for potential application in humans.

The fight against the negative effects of aging is increasingly at the center of the concerns of researchers. Lifestyle changes can improve the health of older people, but alone are not enough to prevent the ailments of old age. The reuse of existing drugs for “geroprotection” provides an additional weapon in the prevention of age-related decline.

The most promising anti-aging drug currently 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, lead researcher of the study in Professor Linda Partridge’s department, director. at the Max Planck Institute for the Biology of Aging.

Only a brief exposure

Scientists tested different time windows of short-term drug administration in fruit flies and found that a brief 2-week window of rapamycin treatment in young adult flies protected them against gut pathologies linked to the disease. age and prolong their life.

A corresponding short time window, 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.

This shows a person holding a bottle of rapamycin
Rapamycin is currently the most promising anti-aging drug. Credit: Max Planck Institute

“These brief drug treatments in early adulthood produced just as strong protection as continuous treatment started at the same time.

“We also found that rapamycin treatment had the strongest and best effects when given in early life compared to middle age. When the flies were treated with rapamycin at the end of their lives, however, it had no effect.

“Thus, rapamycin memory is activated primarily in early adulthood,” says 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 if 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.

See also

This shows a young macaque

“This study opened new doors, but also raised many new questions.”

About this aging and pharmacology research news

Author: Maren Berghoff
Source: Max Planck Institute
Contact: Maren Berghoff – Max Planck Institute
Image: Image is credited to the Max Planck Institute

Original research: Free access.
Long-lasting geroprotection against brief rapamycin treatment in early adulthood through a persistent increase in intestinal autophagy” by Linda Partridge et al. natural aging


Long-lasting geroprotection against brief rapamycin treatment in early adulthood through a persistent increase in intestinal autophagy

Rapamycin, a licensed drug, could be repurposed for geroprotection. One of the main challenges is avoiding the unwanted side effects of continued dosing.

Here we show that the geroprotective effects of chronic rapamycin treatment can be achieved with a brief pulse of the drug in early adulthood in women. Drosophila and smile.

In Drosophila, brief early rapamycin treatment of adults prolonged lifespan and attenuated age-related bowel decline to the same degree as lifelong administration. Lasting memory of prior treatment was mediated by elevated autophagy in intestinal enterocytes, accompanied by increased levels of intestinal LManV and lysozyme.

A brief elevation in autophagy in early adulthood itself induced a long-term increase in autophagy. In mice, an early treatment of 3 months also induced a memory effect, with maintenance similar to chronic treatment, of the distribution of lysozyme, the level of Man2B1 in the intestinal crypts, the architecture of Paneth cells and of intestinal barrier function, even 6 months after discontinuation of rapamycin.

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