MRC Human Genetics Unit
Medical Research Council Human Genetics Unit

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Notch mediates secondary senescence

Novel signalling pathway identified using single cell approaches

graphical overview of primary and secondary oncogene induced senescence in cells

Cellular senescence is a common stress response in aged organs or malfunctioning cells, such as those that might became cancerous. Cellular senescence tries to prevent these cells from harming the organism, for example by preventing cancer. Once cells become senescent, they interact with surrounding cells and induce a “secondary” senescence response in them, spreading senescence within the tissue. However, if senescent cells persist or there are too many of them they can accelerate ageing and age-related disease. The discovery that senescent cells can be harmful has led to research and development in drugs that can specifically eliminate senescent cells, called senolytica.

Examining the RNA in single-cells allowed Tamir Chandra, of the MRC Human Genetics Unit, University of Edinburgh, and colleagues to capture the complex interactions between senescent and non-senescent cells that get lost when measuring at the tissue level. Their research shows that primary and secondary senescent cells are quite distinct from each other, and might fulfil different roles. These findings also raise the question of which cells are responsible for the negative effects seen in the persistence of senescent cells and whether this needs to be considered when developing new drugs (senolytica). The work has revealed an additional mechanism by which cells mediate secondary senescence after cancerous stress, called Notch signalling. Notch signalling relies on cells directly contacting each other. The research also highlights how diverse the senescence response is and how little we know about the role secondary senescence plays in health and disease. 

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Chandra research group

Original article: https://doi.org/10.1016/j.celrep.2019.03.104