Senescence-associated biomarkers (SABs)

Senescence-associated biomarkers are a heterogeneous group of molecular and cellular indicators used to identify and quantify cellular senescence, a state of permanent cell cycle arrest triggered by various forms of stress or damage [1, 4]. These biomarkers encompass cell cycle inhibitors such as p16INK4a and p21CIP1, enzymatic activities like senescence-associated beta-galactosidase (SA-β-gal), and a complex array of secreted factors known as the senescence-associated secretory phenotype (SASP), which includes pro-inflammatory cytokines like IL-6 and IL-8 [2, 7]. While not a single therapeutic target, these markers are essential for the development and monitoring of senotherapies, such as senolytics that eliminate senescent cells and senomorphics that modulate their harmful secretions [3, 6]. The accumulation of senescent cells is a hallmark of aging and is implicated in various chronic conditions, including cancer, neurodegeneration, and cardiovascular disease [8, 12]. Consequently, these biomarkers serve as critical tools for patient stratification and evaluating the efficacy of interventions aimed at extending healthspan and treating age-related pathologies [11, 13].

Other names

Cellular senescence markersSenescence markersMarkers of cellular senescenceSenescence-associated secretory phenotype factorsSASP factors

Senolytics selectively induce apoptosis in senescent cells by inhibiting pro-survival pathways (senescent cell anti-apoptotic pathways or SCAPs), such as the Bcl-2 family (e.g., Bcl-xL), PI3K/Akt, and p53/p21/serpine pathways [4, 5]. Senomorphics suppress the senescence-associated secretory phenotype (SASP) without killing the cells, typically by inhibiting pathways like NF-κB, mTOR, or JAK/STAT [11, 13]. Emerging strategies also include CAR-T cells targeting senescence-specific surface markers like uPAR [1, 12].