Cellular Senescence and Vascular Dysfunction: The Role of Cyclin-Dependent Kinases 4 and 6 (2012)

Undergraduate: Kelly Mitchell

Faculty Advisor: Frank Church
Department: Biology

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Aging is a known important risk factor for developing cardiovascular disease, but the mechanism behind this phenomenon is poorly understood. Furthermore, cellular senescence associated with aging has been linked to vascular dysfunction, in particular venous thrombosis. p16(INK4a), a cell cycle inhibitor that promotes senescence, is upregulated in many tissues during aging, and this upregulation has been found to stimulate a prothrombotic phenotype in vivo. When p16 is activated, it binds to Cyclin-Dependent Kinases 4 and 6, disrupting their ability to phosphorylate the retinoblastoma protein and thus causing cell cycle arrest in growth phase 1. Here, we investigate whether the senescence and prothrombotic activity observed with upregulated p16 also occur when CDK4 and CDK6 are instead silenced directly.