Regulators of Senescence

Rationale for the assay

Senescence is a cellular fail safe response in order to clear or eliminate potential harmful cells. Senescent cells present permanent cell cycle arrest, activation of the tumour suppressor pathways p53-p21 and p16-Rb, altered metabolism reflected in the Senescence Associated b-galactosidase activity, altered chromatin and the activation of a specific proinlammatory secretome termed the Senescence Associated Secretory Phenotype (SASP). During aging, senescent cells are accumulated and disrupt tissue function.

It has been hypothesized that senescent cells contribute to aging by the activation of the SASP. Recently, several reports suggested that elimination of senescent cells in vivo improves detrimental effects in aging and extended quality lifespan. importantly, the senescent phenotype could be reverted (rejuvenation) by targeting some of its regulators such as p16 or p53 or the activation of the SASP by mTOR. Thus, the identification of new pathways regulating replicative senescence promises big potential for the rational design of anti-ageing therapies targeting senescence or senolytics.