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    Experimental Drug TM5441 Prolongs Life Span 4x In Mice
    By News Staff | May 1st 2014 10:44 AM | 1 comment | Print | E-mail | Track Comments

    Rapidly aging mice fed an experimental drug lived more than four times longer than a control group, and their lungs and vascular system were protected from accelerated aging, according to a new study.


    The reason is a protein's key role in cell and physiological aging. The experimental drug inhibits the protein's effect and prolonged the lifespan in a mouse model of accelerated aging. 

    This is a completely different target and different drug than anything else being investigated for potential effects in prolonging life and the experimental drug is in the early stages of testing, they note in Proceedings of the National Academy of Sciences.

    The experimental drug, TM5441, is one of only several chosen each year by the National Institute on Aging to be tested in its Interventions Testing Program, which investigates treatments with the potential to extend lifespan and delay disease in mice.

    When cells or tissue age -- 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 for Northwestern University's Douglas Vaughan, M.D., senior author of the study, 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.



    Comments

    Oh great! Just what I need, is mice that live even longer than they already do.