Towards Ways to Sabotage the Immune Evasion of Senescent Cells in Aged Tissues

Senescent cells are created constantly throughout life, largely the result of somatic cells reaching the Hayflick limit on cellular replication. In youth, these cells are rapidly removed by the immune system, but this clearance falters in later life for reasons yet to be fully explored. Nonetheless, enough is understood to propose a variety of avenues by which the immune clearance of senescent cells can be improved. Cellular senescence is a complex process involving a close-to-irreversible arrest of the cell cycle, the acquisition of the senescence-associated secretory phenotype (SASP), as well as profound changes in the expression of cell surface proteins that determine the recognition of senescent cells by innate and cognate immune effectors including macrophages, NK, NKT, and T cells. It is important to note that senescence can occur in a transient fashion to improve the homeostatic response of tissues to stress. Moreover, both the excessive generation and the insufficient elimination of senescent cells may contribute to pathological aging. Attempts are being made to identify the mechanisms through which senescent cell avoid their destruction by immune effectors. Such mechanisms involve the cell surface expression of immunosuppressive molecules including PD-L1 and PD-L2 to ligate PD-1 on T cells, as well as tolerogenic MHC class-I variants. In addition, senescent cells can secrete factors that attract immunosuppressive and pro-inflammatory cells into the mi...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs