Senescent cell clearance by the immune system: Emerging therapeutic opportunities.

Senescent cell clearance by the immune system: Emerging therapeutic opportunities. Semin Immunol. 2019 May 11;: Authors: Prata LGPL, Ovsyannikova IG, Tchkonia T, Kirkland JL Abstract Senescent cells (SCs) arise from normal cells in multiple organs due to inflammatory, metabolic, DNA damage, or tissue damage signals. SCs are non-proliferating but metabolically active cells that can secrete a range of pro-inflammatory and proteolytic factors as part of the senescence-associated secretory phenotype (SASP). Senescent cell anti-apoptotic pathways (SCAPs) protect SCs from their own pro-apoptotic SASP. SCs can chemo-attract immune cells and are usually cleared by these immune cells. During aging and in multiple chronic diseases, SCs can accumulate in dysfunctional tissues. SCs can impede innate and adaptive immune responses. Whether immune system loss of capacity to clear SCs promotes immune system dysfunction, or conversely whether immune dysfunction permits SC accumulation, are important issues that are not yet fully resolved. SCs may be able to assume distinct states that interact differentially with immune cells, thereby promoting or inhibiting SC clearance, establishing a chronically pro-senescent and pro-inflammatory environment, leading to modulation of the SASP by the immune cells recruited and activated by the SASP. Therapies that enhance immune cell-mediated clearance of SCs could provide a lever for reducing SC burden. Such thera...
Source: Seminars in Immunology - Category: Allergy & Immunology Authors: Tags: Semin Immunol Source Type: research