Study suggests that treating mice with the cancer drug alpelisib can increase their life expectancy by an average of 10%.
A study by researchers at the Waipapa Taumata Rau – University of Auckland in New Zealand indicates that treating middle-aged – so, aged approximately one-year-old – with the compound alpelisib can increase their life expectancy by an average of 10% to about three years.
As well as increased lifespan, the mice exhibited signs of improved healthspan, including improved coordination and strength [1].
Longevity.Technology: Often drugs are created in a disease-oriented paradigm – designed and tested to treat a particular pathological condition. However, a number of drugs have demonstrated pro-longevity effects, including commonly dispensed medications like aspirin, statin, metformin, and the headline-grabber, rapamycin. While there is a wealth of safety data available of these sorts of drugs, translation to humans is often a tricky affair, and there have been some disappointing or inconclusive trials, perhaps suggesting additional translational steps are warranted, and results of larger trials, such as PEARL and TAME should help to guide further research.
The study of alpelisib was not without side effects, so as the authors rightly surmise, human trials are not in the near future, but it further shows the benefits of researching repurposed drugs for longevity.
Alpelisib, a small molecule inhibitor which is sold under the brand name Piqray among others, is used to treat certain types of breast cancer. The drug targets a specific enzyme called PI 3-kinase, and earlier research has shown that targeted suppression of PI3K has led to lifespan extension in rodents and model organisms [2]. Many cancers have excessive activation of this pathway, which is why alpelisib is used therapeutically.
In this study, mice were fed a controlled diet, with some of the mice receiving alpelisib in addition. The results showed that “dietary supplementation with the PI3Ki alpelisib from middle age extends the median and maximal lifespan of mice, an effect that was more pronounced in females … These results suggest that while pharmacological suppression of insulin receptor (IR)/insulin-like growth factor receptor (IGFR) targets could represent a promising approach to delaying some aspects of aging [1].”
Research fellow Dr Chris Hedges said: “Ageing is not only about lifespan but also about quality of life.
“Therefore, we were pleased to see this drug treatment not only increased longevity of the mice but they also showed many signs of healthier ageing. We are working now to understand how this happens [3].”
There were some side effects, including reductions in bone mass and mild hyperglycemia, which means that translation to humans will merit caution.
Principle investigator Associate Professor Troy Merry said: “We are not suggesting that anyone should go out and take this drug long-term to extend lifespan, as there are some side effects.
“However, this work identifies mechanisms crucial to ageing that will be of use in our long-term efforts to increase lifespan and health-span. It also suggests a number of possible ways in which shorter term treatments with this drug could be used to treat certain metabolic health conditions and we are following this up now [3].”
[1] https://www.nature.com/articles/s43587-022-00349-y
[2] https://www.cell-stress.com/researcharticles/2022a-abdellatif-cell-stress/
[3] https://bit.ly/3jI44I5
