Senescence-associated secretory phenotype (SASP) and senescent cell anti-apoptotic pathways (SCAPs) (SASP/SCAPs)

Senescent cell SASP (Senescence-associated secretory phenotype) and survival pathways (Senescent cell anti-apoptotic pathways, or SCAPs) represent a complex network of signaling mechanisms that maintain cells in a state of permanent cell cycle arrest while promoting a pro-inflammatory environment (Kirkland & Tchkonia, 2017, JAMA). The SASP involves the secretion of cytokines (e.g., IL-6, IL-8), chemokines, and matrix metalloproteinases that can induce paracrine senescence and drive chronic inflammaging, contributing to cancer progression and tissue dysfunction (Coppe et al., 2008, PLoS Biology). SCAPs, which include the BCL-2 family (BCL-2, BCL-XL), PI3K/AKT, and p53/p21 pathways, allow these damaged cells to evade apoptosis despite high levels of cellular stress (Zhu et al., 2015, Aging Cell). Therapeutic strategies targeting these pathways include senolytics, which selectively eliminate senescent cells by inhibiting SCAPs, and senomorphics, which suppress SASP components without inducing cell death (Childs et al., 2017, Nature Medicine). These approaches are currently being evaluated in clinical trials for age-related conditions such as idiopathic pulmonary fibrosis, diabetic kidney disease, and osteoarthritis (NCT02848170, NCT04063124).

Other names

Senescence-associated secretory phenotypeSenescent cell anti-apoptotic pathwaysSCAPsSASPSenescent cell survival signaling

Senolytics function by transiently disabling the SCAPs that protect senescent cells from their own pro-apoptotic SASP, typically by inhibiting BCL-2 family proteins or tyrosine kinases like those in the ephrin family (Kirkland & Tchkonia, 2017). Senomorphics, such as mTOR inhibitors or NF-κB blockers, reduce the expression and secretion of deleterious SASP factors to mitigate tissue damage (Laberge et al., 2015).