The SASP is a complex secretory program involving hundreds of factors including inflammatory cytokines, chemokines, growth factors, proteases, and extracellular vesicles. SASP is driven primarily by NF-κB and C/EBPβ transcription factors activated by persistent DNA damage signaling. SASP can spread senescence to neighboring cells ("paracrine senescence"), drive cancer progression, and create a chronic inflammatory state that accelerates nearly every age-related disease.

SASP composition varies by cell type and senescence inducer. Wound healing SASP is temporarily beneficial (promoting tissue repair via PDGF-AA, VEGF). Age-related, chronic SASP is persistently harmful. The distinction is between transient, targeted SASP vs persistent, systemic SASP from accumulated senescent cells.

Anti-inflammatory diets (Mediterranean, high polyphenol) reduce SASP-related markers in clinical studies. However, dietary polyphenol concentrations (quercetin, fisetin, curcumin from food) are far below senolytic threshold — diet reduces SASP expression but cannot eliminate the senescent cells producing it.