07 May 2014

Experimental drug increases the lifespan of mice

Researchers at Northwestern University, working under the leadership of Professor Douglas Vaughan, have identified a protein that plays a key role in the functioning and physiological aging of cells. Together with Japanese colleagues from Tohoku University, they have developed an experimental drug that suppresses the activity of this protein and increases the lifespan of a mouse model of premature aging.

Upon entering the phase of physiological aging, cells lose the ability to divide and secrete certain proteins. One of these proteins, a plasminogen activator inhibitor (PAI–1), has been an object of interest to Vaughan's laboratory staff for 25 years. Initially, he attracted the attention of scientists because of his involvement in the development of diseases of the cardiovascular system.

At the next stage of their work, the researchers suggested that PAI-1, which is a marker of cell aging, may be one of the triggering factors of rapid physiological aging of the body.

In order to test this hypothesis, they bred a line of mice that do not have the Klotho gene that suppresses the aging process. These animals were characterized by signs of premature aging, such as atherosclerosis, neurodegeneration, osteoporosis, emphysema, as well as significantly shortened life expectancy. Blood and tissue analysis of these animals revealed elevated levels of PAI-1.

A subsequent series of experiments showed that the daily addition of the experimental drug TM5441 to the feed of prematurely aging mice reduced the activity of the PAI-1 protein in the body. This increased the life expectancy of animals by 4 times and maintained the health and normal functioning of their organs.

Similar results were obtained when crossing mice without the functional Klotho gene with mice without the functional PAI-1 gene.

The authors believe that the experimental drug they developed could potentially be useful in the treatment of diseases that cause premature aging of a person, such as chronic kidney failure, diabetes and HIV, as well as to neutralize the effects of smoking.

Vaughan notes that this drug and its therapeutic target are fundamentally different from all other compounds and mechanisms being studied for their supposed positive effect on life expectancy. The experimental drug TM5441 is one of several drugs selected annually by the National Institute of Aging for testing as part of the Interventions Testing Program, a program aimed at studying therapeutic approaches that can potentially increase life expectancy and delay the development of age–related diseases in mice.

Article by M. Eren et al. PAI-1-regulated extracellular proteolysis governs senescence and survival in Klotho mice is published in open access in the journal Proceedings of the National Academy of Sciences.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Northwestern University:
Experimental Drug Prolongs Life Span in Mice.


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