A team of researchers from the Max Planck Institute for Biology of Ageing has revealed that brief exposure to the macrolide drug rapamycin could have similar effects on lifespan as lifelong use.
Rapamycin
Rapamycin
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In their study, published in Nature Aging, the scientists found that exposing laboratory animals to the drug in early adulthood had the same anti-aging effects as when administered over their entire lifetime.
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“These brief drug treatments in early adulthood produced just as strong protection as continuous treatment started at the same time,” said co-author Dr. Thomas Leech.
This finding could open the door for using rapamycin to combat aging effects and extend lifespan in humans.
Drug repurposing to fight aging
According to research, lifestyle changes can help people live longer and enjoy good health. However, evidence has shown that these changes alone are not enough to prevent health issues in old age.
Scientists have also been exploring repurposing drugs used for other conditions to combat age-related decline. The most promising drug identified for this purpose is rapamycin.
Typically, rapamycin is used to guard against organ transplant rejection and in cancer therapy.
However, the use of rapamycin comes with risks. Severe side effects can result even from low clinical doses. A drug used to fight aging and increase lifespan should not have these unwanted effects.
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To derive maximum positive effects, this immunosuppressive agent usually needs to be taken as a lifelong treatment.
Dr. Paula Juricic and her colleagues aimed to explore alternatives to lifelong rapamycin use for combating age-related decline.
Brief exposure is beneficial
The researchers tested the drug for different short durations in both fruit flies and mice. A two-week therapy in young adult flies was found to protect against age-related intestinal failure and extend their lives. An equivalent short-term treatment (three months) in mice produced similar intestinal health benefits during middle age.
“We also found that rapamycin treatment had the strongest and best effects when given in early life compared to middle age,” explained Leech. “When flies were treated with rapamycin in late life, however, it had no effects at all. So, the rapamycin memory is activated primarily in early adulthood.”
The researchers noted that their findings make the use of the drug for anti-aging purposes potentially more practical in humans. They suggest some benefits could be obtained without lifelong treatment, which often comes with unpleasant side effects.
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While acknowledging that their research has opened new doors, senior study author Professor Linda Partridge noted that it has also “raised many new questions.” It is critical to determine whether geroprotection similar to that observed in mice could be achieved with later-life treatment in humans, she said. The treatment would need to be brief.
Researchers will also need to explore whether intermittent dosing in humans would produce similar effects.
References
Juricic, P., Lu, YX., Leech, T. et al. Long-lasting geroprotection from brief rapamycin treatment in early adulthood by persistently increased intestinal autophagy. Nat Aging 2, 824–836 (2022). https://doi.org/10.1038/s43587-022-00278-w
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