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New Class of Drugs Improves Lifespans And Health of Mice

BEC CREW
11 MARCH 2015

Mice everywhere rejoice, because have we got the drug for you. Scientists in the US have developed a new class of drugs called ‘senolytics’ which actively treat symptoms of old age and frailty, improve cardiac function, and extend the lifespan of the mice they’ve tested them on.

 

"The prototypes of these senolytic agents have more than proven their ability to alleviate multiple characteristics associated with ageing," said one of the team, James Kirkland from the Mayo Clinic, in a press release. "It may eventually become feasible to delay, prevent, alleviate or even reverse multiple chronic diseases and disabilities as a group, instead of just one at a time."

When we age, our bodies accumulate senescent cells - cells that have lost the capacity to divide but stubbornly refuse to die off. The build-up of these cells make us more susceptible to age-related diseases, and scientists have found that if you kill off the senescent cells in mice, you can actually extend their ‘healthspan' - the amount of time they are free of disease. But how do you develop a drug that can identify and kill off these defective cells, without damaging the healthy ones around them?

The team investigated this problem by looking into the mechanism that keeps senescent cells alive, and found that it’s actually quite similar to the way cancer cells survive so well. Senescent cells have what the researchers call "pro-survival networks", which help them combat the natural processes of apoptosis - or virus infection - and programmed cell death.

Knowing this, they developed drugs based on two compounds - the cancer drug dasatinib, and the anti-inflammatory and antihistamine drug quercetin - which can successfully break down the defences of senescent cells, allowing them to die a natural death. The drugs were found to be effective on both human and mouse cells.

Next, the team was ready to test the drugs on their lab mice. They found that when given a single dose, old mice showed signs of improved cardiovascular function after just five days, and they experienced improved exercise capacity, even after having been weakened by radiotherapy. The effect lasted for seven months. Mice engineered to have accelerated ageing were given periodic doses of the drug, and ended up with an extended healthspan, which delayed the development of age-related disorders such as spine degeneration and osteoporosis. The results were published in the journal Aging Cell.

"In animal models, the compounds improved cardiovascular function and exercise endurance, reduced osteoporosis and frailty, and extended healthspan," said one of the team, Laura Niedernhofer from the Scripps Research Institute. "Remarkably, in some cases, these drugs did so with only a single course of treatment."

Now, of course, this doesn’t mean much until it’s tested on humans, but it’s an intriguing development. The team says that because the accumulation of senescent cells  factors into a number of human diseases and pathologies, it’s a promising prospect to have a drug that just might be able to minimise the build-up of these cells.