Senescence-associated secretory phenotype mediators (SASP)

Senescence-associated secretory phenotype (SASP) mediators are a diverse collection of pro-inflammatory cytokines, chemokines, growth factors, and proteases secreted by cells that have entered a state of permanent cell cycle arrest [1.1.1, 1.1.2]. These factors, which include prominent molecules such as Interleukin-6 (IL-6), Interleukin-8 (IL-8), and various matrix metalloproteinases, play a critical role in the biological aging process and the development of age-related diseases [1.1.1, 1.3.1]. While transient SASP secretion can be beneficial for wound healing and tumor suppression, the chronic accumulation of these mediators leads to persistent low-grade inflammation, known as inflammaging, and promotes tissue dysfunction [1.1.3, 1.3.3]. SASP mediators act through autocrine and paracrine signaling to reinforce the senescent state and induce secondary senescence in neighboring healthy cells [1.1.1, 1.1.5]. In the context of disease, they are implicated in cancer progression, neurodegeneration, and cardiovascular disorders by altering the tissue microenvironment [1.3.4, 1.3.5]. Therapeutic strategies targeting these mediators, termed senomorphics, aim to suppress the production or secretion of SASP factors without inducing apoptosis in the senescent cells [1.2.2, 1.2.5]. Drugs such as rapamycin, metformin, and ruxolitinib modulate upstream signaling pathways like mTOR, NF-κB, and JAK/STAT to dampen the SASP, offering a potential approach to extend healthspan and treat chronic inflammatory conditions [1.2.1, 1.2.3]. Additionally, specific antibodies targeting individual SASP components, such as IL-6 or IL-1, are being explored to mitigate the localized effects of senescent cell accumulation [1.1.5, 1.3.5].

Other names

SASP factorsSenescence-associated secretory phenotypeSenescence messaging secretomeSenescent cell secretome

Inhibition of the production, secretion, or activity of senescence-associated secretory phenotype (SASP) factors by modulating upstream signaling pathways such as mTOR, NF-κB, p38 MAPK, and JAK/STAT [1.2.1, 1.2.3, 1.2.5].