Researchers Develop New Drug Combination to Treat Physical Dysfunction

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Researchers from Mayo Clinic suggest that Senolytic drugs reverse damage caused by senescent cells in mice

Many normal cells continuously grow, die, and replicate. Cell senescence is a loss of cell function, including the ability to divide and replicate. However, these cells still survive and affect neighboring cells as they secrete several pro-inflammatory and tissue remodeling molecules. The number of senescent cells increasing with aging are evident in organs associated with many chronic diseases and after radiation or chemotherapy treatment. The researchers at Mayo Clinic observed that injecting senescent cells into young mice caused loss of health and function. However, treating them with a combination of two existing drugs eliminated the senescent cells from tissues, which in turn restored physical function. Moreover, the aging mice experienced extended life span and health span. The study was published in the journal Nature Medicine on July 9, 2018. Senolytics are a class of drugs capable of selectively eliminating senescent cells. The team combined dasatinib and quercetin (D+Q) to check the efficiency of senolytic combinations to slow physical dysfunction caused by senescent cells. Dasatinib is a chemotherapy medication used to treat certain cases of chronic myelogenous leukemia and acute lymphoblastic leukemia, whereas quercetin is a plant flavonol found in many fruits, vegetables, leaves, and grains.

James L. Kirkland, M.D., Ph.D., of the Mayo Clinic in Rochester and his team observed that injecting small amount of senescent cells in young, healthy mice damage tissues, which in turn results in physical dysfunction. However, dasatinib and quercetin together prevented cell damage and delay physical dysfunction.  Four month-old mice were injected with either senescent (SEN) cells or non-senescent control (CON) cells. After two weeks, the SEN mice showed impaired physical function along with increased numbers of senescent cells, which was a result of propagation of the senescence effect into neighboring cells. Both SEN and CON mice were then treated with D+Q compound mix for three days. It was observed that D+Q selectively eliminated senescent cells, which in turn slowed the deterioration in physical functions. The findings are expected to enhance life span in older people, as well as, in cancer survivors.

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