Genetic Pathways of Senescence

Therapeutics targeting senescence offers great potential in multiple areas, including cancer, stem cell regulation and aging, but is underappreciated largely because senescence is not well understood. We are interested in elucidating the genetic pathways that govern senescence. We use both forward genetic screen and reverse genetics to achieve this goal. We have identified a number of genes that control senescence activation and will continue to search for additional senescence regulators. We are interested in the underlying molecular mechanisms of senescence regulation by these genes. Understanding the genetic pathways of senescence will help us formulating effective therapeutic strategies targeting senescence for cancer and age-dependent pathological conditions.

Notch3 regulates senescence. (A) Elevated expression of Notch3 in senescent human fibroblasts. (B) Down-regulation of Notch3 leads to decreased expression of p21 and extended replicative lifespan in human fibroblasts. (C) Ectopic expression of Notch3 induces p21 expression and senescence.