Rapamycin is a promising anti-aging drug that improves health and lifespan.
Rapamycin, also known as sirolimus, is an immunosuppressant medication that received FDA approval in 1999.
For nearly a decade, researchers have been aware of the drug's ability to increase life expectancy in mice and model organisms.
A recent study looked into whether short-term dosing in early adulthood could have a long-term anti-aging effect with fewer side effects.
Life expectancy has steadily increased over the last 200 years, as has the prevalence of age-related diseases
While lifespan has increased, healthspan has not kept pace. This means that, while we can live longer because of advances in our environments and medical and biological sciences, the number of years we spend without age-related health conditions has not increased proportionally.
One reason for this is that the processes underlying aging-related health decline are poorly understood and difficult to control.
There are several theories as to why we age and become more prone to cardiovascular disease, Type 2 Diabetes (T2D), cataracts, hearing loss, and dementia, as well as a decrease in immunity and muscle mass.
Diverse theories about the causes of aging exist, 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 suggested to improve older people's health, they are insufficient to prevent age-related decline. Furthermore, lifestyle interventions can be difficult to maintain. As a result, scientists are investigating the potential of pharmaceutical interventions.
Rapamycin as an anti-aging treatment?
Rapamycin is one of these possible pharmaceutical interventions. It was first approved by the FDA in 1999 as an immunosuppressant for transplant patients under the brand name sirolimus. Rapamycin was also discovered to have anti-cancer properties by researchers.
Another property of the drug was eventually discovered: longevity and a reduction in age-related disease.
Dr. Mikhail Blagosklonny, an aging researcher at the Roswell Park Comprehensive Cancer Center in Buffalo, NY, first proposed in the journal Cell Cycle in 2006 that Rapamycin could potentially inhibit the aging process.
A study conducted by Novartis and Stanford University, CA, and published in Science Translational Medicine in 2014, confirmed his hypothesis.
He highlighted that the next question was whether giving Rapamycin at a specific point in early adulthood could have long-term effects.
This is exactly what researchers from the Max Planck Institute for Biology of Ageing in Cologne, Germany investigated in fruit flies and mice in a recent paper. The study was published in Nature Aging.
"At the clinical doses used, Rapamycin can have undesirable side effects, but these must be absent or minimal for the drug to be used in the prevention of age-related decline. As a result, we wanted to know when and how long we needed to give Rapamycin to achieve the same effects as lifelong treatment," says Dr. Paula Juricic, the study's principal investigator from the Max Planck Institute for Biology of Ageing.
The researchers discovered that giving Rapamycin to young adult drosophila, a type of fruit fly used as a genetic model organism, for two weeks protected them from age-related changes in the intestine and extended their lives.
They discovered that this was due to an increase in the intestine's autophagy mechanisms, which are responsible for recycling parts of the cell that have become defective. According to the researchers, this upregulation was sustained and was caused by cells in the intestine retaining a memory of the drug.
The drug was also administered to mice for three months beginning at three months of age, which corresponds to early adulthood, and improvements in gut barrier integrity were observed in middle age. They also discovered that the drug's effects could still be detected 6 months after they stopped taking it.
Questions remain unanswered
Dr. Dao-Fu Dai, assistant professor of pathology at the University of Iowa Health Care and a researcher on the effect of Rapamycin in mice, called the paper "exciting," but said the next step would be to see how reproducible the results in drosophila would be in a mammalian system.
In an interview with Medical News Today, he stated:
"I believe the paper is very interesting. Things that will need to be done in the future will involve [the] mammalian system, because drosophila is much easier to do than mammals. Doing it in mammals is somewhat limited because they only focus on [the] intestinal system and then look at the gut barrier system in mammals because the entire drosophila story is based on protecting the gut barrier system [in this study]."
Dr. Alessandro Bitto, 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 give Rapamycin for a lifelong effect in mammals.
"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 lifelong intervention?" he said.
This would reduce the amount of drug that would need to be administered in total, reducing risks and potentially problematic side effects.
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