Wednesday, March 11, 2015

Scientists Find New Class of Drugs that Dramatically Increases Healthy Lifespan

A research team from The Scripps Research Institute (TSRI), Mayo Clinic and other institutions has identified a new class of drugs that in animal models dramatically slows the aging process—alleviating symptoms of frailty, improving cardiac function and extending a healthy lifespan.

The new research was published March 9 online ahead of print by the journal Aging Cell. The scientists coined the term “senolytics” for the new class of drugs.

“We view this study as a big, first step toward developing treatments that can be given safely to patients to extend healthspan or to treat age-related diseases and disorders,” said TSRI Professor Paul Robbins, PhD, who with Associate Professor Laura Niedernhofer, MD, PhD, led the research efforts for the paper at Scripps Florida. “When senolytic agents, like the combination we identified, are used clinically, the results could be transformative.”

“The prototypes of these senolytic agents have more than proven their ability to alleviate multiple characteristics associated with aging,” said Mayo Clinic Professor James Kirkland, MD, PhD, senior author of the new study. “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.”
 
Finding the Target
Senescent cells—cells that have stopped dividing—accumulate with age and accelerate the aging process. Since the “healthspan” (time free of disease) in mice is enhanced by killing off these cells, the scientists reasoned that finding treatments that accomplish this in humans could have tremendous potential.

The scientists were faced with the question, though, of how to identify and target senescent cells without damaging other cells.

The team suspected that senescent cells’ resistance to death by stress and damage could provide a clue. Indeed, using transcript analysis, the researchers found that, like cancer cells, senescent cells have increased expression of “pro-survival networks” that help them resist apoptosis or programmed cell death. This finding provided key criteria to search for potential drug candidates.

Using these criteria, the team homed in on two available compounds—the cancer drug dasatinib (sold under the trade name Sprycel®) and quercetin, a natural compound sold as a supplement that acts as an antihistamine and anti-inflammatory.

Further testing in cell culture showed these compounds do indeed selectively induce death of senescent cells. The two compounds had different strong points. Dasatinib eliminated senescent human fat cell progenitors, while quercetin was more effective against senescent human endothelial cells and mouse bone marrow stem cells. A combination of the two was most effective overall.

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