Deciphering the mechanism for induction of senescence-associated secretory phenotype (SASP) and its role in aging and cancer development.

Cellular senescence is an irreversible form of cell cycle arrest that can be induced by persistent DNA damage, and is well known to function as an important tumor suppression mechanism. Cellular senescence is detected in aged organisms; thus, it is also recognized as a hallmark of organismal aging. Unlike apoptotic cells, senescent cells can survive for long periods of time. Recently, it has been shown that the late stage of senescent cells are capable of expressing a variety of secreted proteins such as cytokines, chemokines, and proteases, and this condition is now known as senescence-associated secretory phenotype (SASP). These secreted factors are involved in myriad of physiological functions including tissue repair and clearance of damaged cells. Alternatively, these factors may promote detrimental effects, such as chronic inflammation or cancer progression, should the SASP phenotype persist. Recent scientific advances have indicated that innate immune responses, particularly involving the cGAS-STING pathway, trigger SASP induction. Therefore, developing a strategy to regulate SASP may provide scientific insights for the management of age-associated diseases and the implementation of healthy aging in the future.