SASP (Senescence-Associated Secretory Phenotype)

SASP biology was extensively characterised by Judith Campisi (Buck Institute) and Jan van Deursen (Mayo Clinic) over the last decade. SASP has paradoxical aspects:

Positive physiological function (short-term): communication with immune cells for elimination of damaged cells, tissue regeneration, pregnancy (senescent cells participate in uterine remodelling), wound healing. Pathological damage (chronification): when senescent cells are not eliminated (immunosenescence failure with age), their chronic SASP damages neighbouring tissue, induces paracrine senescence ('contagion effect'), and perpetuates inflammation.

Chronic SASP consequences in ageing: Extracellular matrix degradation: SASP MMPs degrade collagen and elastin, contributing to wrinkles and loss of arterial elasticity. Senescence propagation: IL-6 and other cytokines induce senescence in previously healthy neighbouring cells. Systemic inflammation: SASP cytokines escape into the bloodstream, contributing to inflammaging. Paradoxical tumour promotion: although senescence is an anti-cancer mechanism, chronic SASP facilitates progression of pre-existing adjacent tumours via growth factors.

Strategies to reduce SASP: Senolytics: selective elimination of senescent cells (D+Q, fisetin, navitoclax). Senomorphs: SASP modulation without killing the senescent cell. Rapamycin (mTOR inhibits SASP), metformin (via AMPK), JAK inhibitors, MK2 inhibitors. NF-κB modulation: SIRT1 (NAD+/resveratrol), curcumin, omega-3 — reduce the SASP master switch. Immunomodulators: improvement of NK and macrophage function for physiological elimination of senescent cells.