A true fountain-of-youth drug combo?

This is really, really interesting. Can we alleviate the effects of aging by getting rid of "bad" cells in the body?

A new study from the Mayo Clinic and the Scripps Research Institute reports that a novel cocktail of two unrelated drugs 
dramatically slows the aging process—alleviating symptoms of frailty, improving cardiac function and extending a healthy lifespan.” 
The scientists who conducted the study, led by James Kirkland, Laura Niedernhofer, and Paul Robbins, screened 46 different compounds to find ones that would interfere with the ability of senescent cells to survive. The two that seemed to work best were quercetin and dasatinib. They call these drugs "senolytic" for their ability to kill senescent cells.

Old cells are supposed to die and let the body replace them. Most of them do, but some cells become senescent: old geezers who just won’t go away. The problem is, these cells just don’t sit quietly in the living room reading a book. Instead, they make lots of noise, throwing things around that can mess up the living room and make all the other cells miserable. At a molecular level, they secrete enzymes that cause inflammation and other problems, which may explain the relationship between these cells and age-related chronic diseases such as heart disease and osteoporosis. 

This current line of research started about four years ago, when the Mayo Clinic's Jan van Deursen published a study (in mice) showing that if you could selectively destroy senescent cells, the mice had fewer age-related diseases and lived up to 25% longer. Senescent cells, it seems, are definitely a problem.

The challenge is that very few cells are senescent, even in very old people, and it's difficult to destroy these cells without harming all the healthy cells around them. In the new study, Kirkland and his team screened 46 different compounds to find ones that could interfere with what they called “pro-survival” genes in senescent cells. The theory is that the senescent cells have a special ability to survive, and if we can interfere with that ability, the cells will die.

The two compounds they found are very different. Quercetin is a common plant extract, found in a wide variety of fruits and vegetables, especially capers, red onions, plums, and cranberries. Dasatinib, in contrast, is a highly specialized cancer drug made by Bristol-Myers Squibb (NYSE:BMY) and sold under the name Sprycel®. Dasatinib is used to treat CML, a form of leukemia. Quercetin is cheap and easily available, while dasatinib is very expensive and cannot be obtained without a prescription.

The study results were very impressive: after a single dose, mice had improved heart function that lasted up to 7 months. Periodic doses worked too: mice showed improvements in a wide range of age-related symptoms, including bone loss, tremors, grip strength, and overall body condition.

Before everyone runs out and buys a giant bag of red onions (or a quercetin supplement), I should inject a dose of skepticism. Quercetin’s effect on lifespan has been studied before, and it came up short. A study in 2013 by Stephen Spindler and colleagues looked at extracts of blueberry, pomegranate, green tea, black tea, quercetin, and other plants, feeding each of them to mice in a controlled experiment. None of the mice lived longer, and Spindler reported that 
our results do not support the idea that isolated phytonutrient anti-oxidants and anti-inflammatories are potential longevity therapeutics.”

However, the method of delivery for quercetin and dasatinib in the new experiment was different, and the combination of the two might have benefits that quercetin alone does not offer. As Kirkland point out, dasatinib and quercetin “are both approved for use in humans and appear to be relatively safe,” although they then go on to point out a variety of possible side effects, some of them harmful. They end, though, on a remarkably optimistic note: 
If senolytic agents can indeed be brought into clinical application, they could be transformative. With intermittent short treatments, it may eventually become feasible to delay, prevent, alleviate, or even reverse multiple chronic diseases and disabilities as a group, instead of one at a time.”
Of course, results in mice often fail when we try them out in humans–but not always. Let’s hope this drug combination shows the same effects in humans that Kirkland and colleagues observed in mice. None of us are getting any younger.

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