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Experimental drug prolongs life span in mice
Date:5/1/2014

by Vaughan's lab.

When cells or tissue age -- called senescence -- they lose the ability to regenerate and secrete certain proteins, like a distinctive fingerprint. One of those proteins, PAI-1 (plasminogen activator inhibitor) has been the focus of Vaughan's research, originally as it relates to cardiovascular disease.

"We made the intellectual leap between a marker of senescence and physiological aging," Vaughan said. "We asked is this marker for cell aging one of the drivers or mechanisms of rapid physiological aging?"

For the study, he and colleagues used mice bred to be deficient in a gene (Klotho) that suppresses aging. These mice exhibit accelerated aging in the form of arteriosclerosis, neurodegeneration, osteoporosis and emphysema and have much shorter life spans than regular mice. Vaughan determined that these rapidly aging mice produce increased levels of PAI-1 in their blood and tissue.

Then scientists fed the rapidly aging mice TM5441 -- the experimental drug -- in their food every day. The result was a decrease in PAI-1 activity (the aging protein Vaughan's team had identified), which quadrupled the mice's life span and kept their organs healthy and functioning.

Northwestern scientists also genetically produced the same life prolonging results when they crossed the mice deficient in the age-suppressing gene with mice deficient in PAI-1. Importantly, partial genetic deficiency of PAI-1 and the experimental PAI-1 antagonist produced provided similar benefits in the mice, Vaughan noted.


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Contact: Marla Paul
marla-paul@northwestern.edu
312-503-8928
Northwestern University
Source:Eurekalert

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