- Rapamycin, also known as sirolimus, is an immunosuppressant 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 brief period in early adulthood could have a lifelong anti-aging impact, with fewer side effects.
Life expectancy has increased steadily over the past 200 years, and along with it, the incidence of age-related disease.
While lifespan has increased, the so-called healthspan has not kept pace. This means that while we are able to live longer due to advances in our environments and medical and biological sciences, the number of years we spend without age-related health conditions has not increased proportionately.
Part of the reason for this is that the processes that underpin the health decline that occurs with aging are poorly understood and difficult to control.
As we age we are more likely to experience cardiovascular disease, type 2 diabetes, cataracts, hearing loss, and dementia, as well as a decrease in immunity and muscle mass, and there are a number of theories as to why.
There are divergent theories about the causes of aging, and different researchers are focusing on different targets to prevent or slow aging in order to improve health in old age, and potentially increase longevity.
While lifestyle changes are recommended to improve health in older people, they are not sufficient to prevent age-related decline. Also, lifestyle interventions can be challenging to maintain. Thus, researchers are looking at the potential of pharmaceutical interventions.
Rapamycin: A potential anti-aging drug?
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. 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 Cell Cycle in 2006 by Dr. Mikhail Blagosklonny, a researcher on aging at the Roswell Park Comprehensive Cancer Center in Buffalo, NY.
His hypothesis was confirmed by a study carried out by researchers at Novartis and Stanford University, CA, and published in Science Translational Medicine in 2014.
Speaking to Medical News Today, he said the next question was whether or not giving rapamycin at a particular point in early adulthood could have long lasting effects.
This is exactly what a recent paper by researchers from the Max Planck Institute for Biology of Ageing, in Cologne, Germany has looked at, in fruit flies and mice. The paper appears in Nature Aging.
Dosing rapamycin for protective effects
“At the doses used clinically, rapamycin can have undesirable side effects, but for the use of the drug in the prevention of age-related decline, these need to be absent or minimal. Therefore, we wanted to find out when and how long we need to give rapamycin in order to achieve the same effects as lifelong treatment,” explains Dr. Paula Juricic, the leading investigator on this study.
Dr. Juricic works in the department of Prof. Dame Linda Partridge, director at the Max Planck Institute for Biology of Ageing.
The study authors found that when young adult drosophila, a type of fruit fly used as a genetic model organism, received rapamycin for 2 weeks, the drug appeared to protect them against age-related changes found in the intestine and extended their lives.
They showed that this was due to an upregulation of the mechanisms in the cell responsible for recycling parts of the cell that have become defective called autophagy, in the intestine. This upregulation was persistent and due to the cells in the intestine retaining a memory of the drug, the authors said.
The drug was also given to mice for 3 months starting at 3 months of age, equivalent to early adulthood, and improvements were seen in the integrity of the gut barrier in middle age. They also found that the effects of the drug could still be detected 6 months after they stopped the treatment.
Unanswered questions
Dr. Dao-Fu Dai, assistant professor of pathology at the University of Iowa Health Care, who has carried out research on the effect of rapamycin in mice, said the paper was “exciting,” but noted that the next step would be to see how reproducible the results in drosophila would be in a mammalian system.
He told Medical News Today in an interview:
“I think the paper is very exciting. The things that need to be done in the future will involve [the] mammalian system, right, because drosophila is much easier to do; mammals take much longer time. Doing it in mammals is rather limited because they only focus on [the] intestinal system and then they look at the gut barrier system in mammals because the whole drosophila story is also based on protecting the gut barrier system [in this study].”
Dr. Alessandro Bitto, acting instructor in the Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, who has also studied the effect of rapamycin in mice, said that identifying when to give rapamycin for a lifelong effect in mammals was a difficult issue.
Lifelong intervention with rapamycin has an effect due to a higher drug dose, he explained: “The question is, is there 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 lifelong intervention?”
This would reduce the amount of the drug that would need to be given overall, and hopefully reduce risks and problematic side effects.
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