An Example of Senomorphic Drug Discovery

Senescent cell accumulation is a feature of aging, a growing imbalance between the rate of creation and rate of destruction. Senescent cells perform a number of useful tasks in the short-term, but when present for the long-term, their inflammatory secretions disrupt tissue function and contribute meaningfully to the onset and progression of age-related disease. A great many research groups are working towards the basis for therapies that can selectively destroy senescent cells (senolytics). Others are working on ways to prevent cells from becoming senescent, or suppress the worst of the bad behavior of existing senescent cells (senomorphics). The open access paper here is a representative example of the latter development process. The senescence-associated secretory phenotype (SASP) is a striking characteristic of senescence. Accumulation of SASP factors causes a pro-inflammatory response linked to chronic disease. Suppressing senescence and SASP represents a strategy to prevent or control senescence-associated diseases. Here, we identified a small molecule SR9009, a specific agonist of NR1D1/NR1D2, as a potent SASP suppressor in therapy-induced senescence (TIS) and oncogene-induced senescence (OIS). The mechanism studies revealed that SR9009 inhibits the SASP and full DNA damage response (DDR) activation through the activation of the NRF2 pathway, thereby decreasing the ROS level by regulating the expression of antioxidant enzymes. We further identified that ...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs