Senescence-associated surface antigens (SASA)

Senescence-associated surface antigens (SASA), also known as senescence-specific surface antigens, are a heterogeneous group of proteins that are significantly upregulated on the plasma membrane of cells undergoing cellular senescence. These antigens, which include prominent members such as Dipeptidyl peptidase 4 (DPP4), Urokinase-type plasminogen activator receptor (uPAR), and Glycoprotein nonmetastatic melanoma protein B (GPNMB), provide a molecular handle for the selective identification and therapeutic elimination of senescent cells, a strategy known as senolysis (Kim et al., 2017; Amor et al., 2020). The accumulation of senescent cells is a hallmark of aging and is implicated in the pathogenesis of numerous chronic diseases through the secretion of a pro-inflammatory cocktail known as the senescence-associated secretory phenotype (SASP). Therapeutic strategies targeting SASAs, such as chimeric antigen receptor (CAR) T cells, antibody-drug conjugates (ADCs), and senolytic vaccines, aim to clear these "zombie cells" to restore tissue homeostasis and alleviate age-related pathologies like pulmonary fibrosis, atherosclerosis, and metabolic dysfunction (Suda et al., 2021). However, the clinical application of SASA-targeted therapies faces challenges regarding the specificity of these markers, as many are also expressed in healthy tissues or are required for normal physiological processes like wound healing and embryonic development (Demaria et al., 2014).

Other names

Senescence-specific surface antigensSSSASASASenescence-associated surface markersSenescent cell surface markers

Selective elimination of senescent cells (senolysis) via immune-mediated cytotoxicity (e.g., CAR-T cells), antibody-dependent cellular cytotoxicity (ADCC), or the targeted delivery of cytotoxic payloads (e.g., antibody-drug conjugates) to cells expressing these markers (Amor et al., 2020; Suda et al., 2021).