- Rapamycin, also known as sirolimus, is an immunosuppressive drug that was approved by the Food and Drug Administration (FDA) in 1999.
- Researchers have known about the drug’s ability to increase life expectancy in mice and model organisms for nearly a decade.
- A recent study has investigated whether dosing for a short period in early adulthood could have a lifelong anti-aging impact, with fewer side effects.
Although life expectancy has increased, the so-called
Part of the reason for this is that the processes that underpin the decline in health that occurs with aging are poorly understood and difficult to control.
There are divergent theories about the causes of aging, and different researchers are focusing on different goals to prevent or delay aging in order to improve health in old age and potentially increase longevity.
While lifestyle changes are recommended to improve the health of older people, they are not enough to prevent age-related decline. Furthermore, lifestyle interventions can be difficult to maintain. Therefore, researchers are looking at the potential of pharmaceutical interventions.
One of these potential pharmaceutical interventions is the use of rapamycin. Also known as sirolimus, it was initially approved by the FDA in 1999 as an immunosuppressant for transplant patients. The researchers also found that rapamycin had anticancer properties.
Eventually, yet another property of the drug was discovered: longevity and a reduction in age-related disease.
Evidence that rapamycin could potentially inhibit the aging process was first proposed in the journal Cellular cycle in 2006 by Dr Mikhail Blagosklonnyresearcher on aging at the Roswell Park Comprehensive Cancer Center in Buffalo, New York.
His hypothesis was confirmed by a study conducted by researchers at Novartis and Stanford University, CA, and published in Science Translational Medicine in 2014.
speaking to Today’s medical newsHe said the next question was whether or not giving rapamycin at a particular point in early adulthood might have lasting effects.
This is exactly what a recent paper by researchers at the Max Planck Institute for the Biology of Aging in Cologne, Germany, has looked at in fruit flies and mice. The paper appears in
“At doses used clinically, rapamycin can have undesirable side effects, but for the drug’s use in preventing age-related decline, these should be absent or minimal. So we wanted to know when and for how long we should give rapamycin to achieve the same effects as lifelong treatment.” Dr. Paula Juricicthe principal investigator of this study.
Dr. Juricic works in the department of Prof Dame Linda Partridgedirector of the Max Planck Institute for the Biology of Aging.
The study authors found that when young adult drosophila, a type of fruit fly used as a genetic model organism, were given rapamycin for 2 weeks, the drug appeared to protect them against age-related changes found in the gut and prolonged their lives.
They showed that this was due to an upregulation of mechanisms in the cell responsible for recycling parts of the cell that have become defective, called autophagy, in the gut. This upregulation was persistent and was because cells in the gut retained the memory of the drug, the authors said.
The drug was also administered to mice for 3 months starting at 3 months of age, equivalent to early adulthood, and improvements in gut barrier integrity were seen in midlife. They also found that the effects of the drug could still be detected 6 months after stopping treatment.
Dr. Dao-Fu Daiassistant professor of pathology at the University of Iowa Health Care, who has conducted research on the effect of rapamycin on mice, called the paper “exciting” but noted that the next step would be to see how reproducible the results in drosophila would be in a mammalian system.
He said Today’s medical news In an interview:
“I think the article is very exciting. The things that must be done in the future will involve [the] mammalian system, correct, because drosophila is much easier to do; mammals take much longer. Doing it in mammals is pretty limited because they only focus on [the] intestinal system and then they analyze the intestinal barrier system in mammals because the whole history of drosophila is also based on protecting the intestinal barrier system [in this study].”
Dr. Alessandro BittoActing instructor in the Department of Laboratory Medicine and Pathology at the Washington University School of Medicine, who also studied the effect of rapamycin in mice, said identifying when to give rapamycin for a lifelong effect in mammals was an issue. hard.
The lifetime intervention with rapamycin has an effect due to a higher dose of the drug, he explained: “The question is, is there a period of treatment in a mouse or a mammal in general where if we give rapamycin in that window we have the same effect, as a lifetime intervention?”
This would reduce the amount of the drug that would need to be administered overall, and hopefully reduce risks and troublesome side effects.