Senomorphic

What it does

A senomorphic agent suppresses the SASP — the inflammatory and remodelling factors that senescent cells secrete — without killing the cell itself. The cell remains senescent (not dividing) but becomes "quieter" and stops driving local and systemic damage.

Major senomorphics

• Rapamycin — the most-studied; partially suppresses SASP via mTOR inhibition.
• JAK inhibitors (ruxolitinib, tofacitinib) — block JAK-STAT signalling downstream of SASP cytokines.
• NF-κB inhibitors (parthenolide, others).
• Metformin — senomorphic effects via AMPK / mTOR.
• Resveratrol, fisetin — some senomorphic activity in addition to senolytic effects.
• STING inhibitors — emerging class.

Senolytic vs senomorphic trade-offs

Feature	Senolytic	Senomorphic
Cell burden	Reduced	Unchanged
Effect duration per dose	Long (hit-and-run)	Short (continuous needed)
Cell-population risks	Loss of beneficial senescent cells	None (cells remain)
Side-effect burden	Acute (e.g. haematological)	Chronic (e.g. immunosuppression)
Clinical examples	D+Q, fisetin	Rapamycin, ruxolitinib

Practical implication

Different patient situations favour different approaches. Acute, high- load senescence (post-radiation, post-chemo) may favour senolytic clearance. Chronic low-grade SASP from background aging may be better managed by continuous senomorphic therapy.

Related entries

Senolytics, Senotherapeutic, Cellular senescence, Rapamycin.