Senescence-associated secretory phenotype factors (SASP)

Senescence-associated secretory phenotype (SASP) factors consist of a complex and heterogeneous mixture of cytokines, chemokines, growth factors, and proteases secreted by cells undergoing permanent cell cycle arrest. While cellular senescence initially serves as a vital tumor-suppressive mechanism and aids in acute wound healing, the chronic accumulation of senescent cells leads to a persistent secretion of these factors, driving chronic low-grade inflammation known as "inflammaging." Major components of the SASP, such as IL-6, IL-1α, and various matrix metalloproteinases, can disrupt tissue architecture and promote age-related pathologies including atherosclerosis, neurodegeneration, and metabolic dysfunction. In oncology, the SASP exhibits a dual role; it can recruit immune cells to clear damaged cells but may also foster a permissive microenvironment that stimulates the growth and metastasis of neighboring malignant cells. Therapeutic interventions known as senomorphics (or senostatics) target the signaling pathways regulating SASP production—such as the NF-κB, mTOR, and JAK/STAT pathways—to suppress the deleterious effects of the secretome without eliminating the senescent cells themselves.

Other names

SASPSenescence messaging secretomeSMSSenescent cell secretomePro-inflammatory secretome

Inhibition of SASP production (Senostasis) by modulating upstream regulatory signaling pathways including NF-κB, mTOR, p38 MAPK, and JAK/STAT signaling [3, 4, 9].