Rapamycin: The next anti-aging drug?

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In an effort to extend longevity and promote healthier aging, scientists are turning to rapamycin. Image credit: miwa_in_oz/Getty Images.
  • 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 investigated whether dosing for a brief period in early adulthood could have a lifelong anti-aging impact, with fewer side effects.

Life expectancy has increased steadily in recent years 200 yearsand with it the incidence of age-related disease.

As the lifespan increased, the so-called lifetime didn’t keep up. This means that although we are able to live longer thanks to advances in our environment and in medical and biological sciences, the number of years we spend without age-related health problems has not increased commensurately.

This is partly because the processes underlying the decline in health that occurs with aging are poorly understood and difficult to control.

As we age, we are more likely to suffer from cardiovascular disease, type 2 diabetes, cataracts, hearing loss and dementia, as well as decreased immunity and muscle mass, and there are some number of theories explaining why.

There are differing theories about the causes of aging, and different researchers focus on different targets to prevent or slow aging in order to improve health in later life and potentially increase longevity.

Although lifestyle changes are recommended to improve the health of older adults, they alone are not enough to prevent age-related decline. Additionally, lifestyle interventions can be difficult to maintain. Thus, researchers are investigating the potential of pharmaceutical interventions.

One such potential pharmaceutical intervention is the use of rapamycin. Also known as sirolimus, it was originally approved by the FDA in 1999 as an immunosuppressant for transplant patients. The researchers also found that rapamycin had anti-cancer properties.

Eventually, another property of the drug was discovered: longevity and a reduction in age-related diseases.

Evidence that rapamycin could potentially inhibit the aging process was first offered in the review Cell cycle in 2006 by Dr. Mikhail Blagosklonny, an aging researcher at Roswell Park Comprehensive Cancer Center in Buffalo, NY.

His hypothesis was confirmed by a study conducted by researchers from Novartis and Stanford University, CA, and published in Science Translational Medicine in 2014.

Talk to Medical News Todayhe said the next question was whether giving rapamycin at some point in early adulthood could have lasting effects.

That’s exactly what a recent paper by researchers at the Max Planck Institute for the Biology of Aging, Cologne, Germany, looked at in fruit flies and mice. The paper appears in natural aging.

“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 give rapamycin to get the same effects as a lifelong treatment,” says Dr. Paula Juricic, the principal investigator of this study.

Dr Juricic works in the department of Professor Dame Linda Partridge, Director 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 the age-related changes found in the intestine and prolonged their life.

They showed that this was due to an upregulation of the cell’s mechanisms responsible for recycling parts of the cell that have become defective, called autophagy, in the intestine. This upregulation was persistent and due to gut cells retaining a memory of the drug, the authors said.

The drug was also given to mice for 3 months from 3 months of age, which is equivalent to early adulthood, and improvements were observed in the integrity of the gut barrier at the middle age. They also found that the effects of the drug could still be detected 6 months after stopping treatment.

Dr Dao-Fu Dai, an assistant professor of pathology at the University of Iowa Health Care who has conducted research on the effect of rapamycin in mice, said the article was “exciting”, but noted that the next step would be to see how reproducible the Drosophila results would be in a mammalian system.

He said Medical News Today in an interview:

“I think the paper is very exciting. Things that need to be done in the future will involve [the] mammalian system, it is true, because Drosophila is much easier to make; mammals take much longer. Doing so in mammals is rather limited as they only focus on [the] intestinal system and then they look at the intestinal barrier system in mammals because the whole story of drosophila is also based on the protection of the intestinal barrier system [in this study].”

Dr Alessandro Bitto, an acting instructor in the Department of Laboratory Medicine and Pathology at the University of Washington School of Medicine who has also studied the effect of rapamycin in mice, said it was difficult to determine when to administer rapamycin for a lifelong effect in mammals. publish.

Lifetime intervention with rapamycin has an effect due to a higher drug dose, he explained: “The question is whether there is a treatment period in a mouse or a mammal in general where if we give rapamycin in this window, we have the same effect, like Lifetime Intervention?

This would reduce the amount of drug that would need to be given overall and hopefully reduce the risks and problematic side effects.

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