PI3K Inhibition Modestly Extends Life in Mice

Long term treatment of mice that results in a modest extension of life span, such as the example here involving inhibition of a subunit of PI3K, is unlikely to be interesting as a basis for human medicine to target aging. Life span is more plastic in short-lived mammals in response to altered metabolic states. Of the known approaches to slowing aging where one can compare humans and mice directly, there is no large extension of life in humans. The most interesting approaches to aging are those that can be applied very intermittently later in life, and which repair damage or enhance function sufficiently well for even one treatment to improve matters noticeably. Senolytics or the restoration of stem cell and immune function following the use of CASIN, for example.

Treatment of healthy mice from middle-age (one year) with alpelisib, a cancer drug that targets the p110α subunit of an enzyme called PI3K, can increase their lifespan by an average of ten percent. In this study, mice were fed a control diet or the same diet with the addition of a drug called alpelisib. Not only did the mice fed the drug containing diet live longer, they showed some signs of being healthier in old age such as improved coordination and strength. However, the researchers are cautious about application to humans since the mice treated with the drug also had some negative markers of ageing like lower bone mass.

"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."

Link: https://www.auckland.ac.nz/en/news/2023/01/25/scientists-identify-drug-that-could-extend-lifespan.html