Cell-cell communication in senescence
Masashi Narita
Cancer Research UK, Cambridge Institute
University of Cambridge
Cellular senescence is a highly stable state of cell cycle arrest induced by various pathophysiological stimuli. Senescent cells typically exhibit distinct morphological changes, and a number of biochemical and molecular markers of senescence have been described, which are typically associated with the effector mechanisms of senescence. Our group is interested in various aspects of such senescence effectors, and how they are related with each other. Senescence is recognised as an ‘autonomous’ tumour suppressor mechanism, and we speculate that the stable nature of the senescence arrest might be, in part, regulated through a fundamental re-organisation of the high-order chromatin structure.Accumulating evidence indicates that senescent cells also have ‘non-autonomous’ activities that exhibit diverse effects upon neighbouring cells and the surrounding tissues through the senescence-associated secretory phenotype (SASP). In addition, our recent evidence suggests that direct cell-cell contact also plays a role in the non-autonomous functions of senescence. Importantly, some aspects of the senescence phenotype can be transmitted to neighbouring ‘normal’ cells through the cell-cell contact. Thus the SASP and cell-cell contact in combination might be a target for modulating senescence and its associated disorders.
I have no financial relationships to disclose
Masashi Narita
Cancer Research UK, Cambridge Institute
University of Cambridge
Cellular senescence is a highly stable state of cell cycle arrest induced by various pathophysiological stimuli. Senescent cells typically exhibit distinct morphological changes, and a number of biochemical and molecular markers of senescence have been described, which are typically associated with the effector mechanisms of senescence. Our group is interested in various aspects of such senescence effectors, and how they are related with each other. Senescence is recognised as an ‘autonomous’ tumour suppressor mechanism, and we speculate that the stable nature of the senescence arrest might be, in part, regulated through a fundamental re-organisation of the high-order chromatin structure.Accumulating evidence indicates that senescent cells also have ‘non-autonomous’ activities that exhibit diverse effects upon neighbouring cells and the surrounding tissues through the senescence-associated secretory phenotype (SASP). In addition, our recent evidence suggests that direct cell-cell contact also plays a role in the non-autonomous functions of senescence. Importantly, some aspects of the senescence phenotype can be transmitted to neighbouring ‘normal’ cells through the cell-cell contact. Thus the SASP and cell-cell contact in combination might be a target for modulating senescence and its associated disorders.
I have no financial relationships to disclose
