Rapamycin vs Senolytics

Rapamycin: senomorphic

• Inhibits mTORC1 (and partially mTORC2 in some tissues).
• Dampens SASP output from existing senescent cells.
• Preserves stem-cell function.
• Extends mouse lifespan across strains (ITP data).
• Human weekly dosing 3–6 mg is the emerging longevity protocol; PEARL trial safety.

Senolytics: cell-clearance

• Selectively kill senescent cells that have upregulated anti-apoptotic pathways.
• Dasatinib + quercetin (D+Q): broad-spectrum; trialled in IPF, diabetic kidney disease.
• Fisetin: cleaner safety profile; NIH-funded RCTs ongoing.
• Navitoclax and derivatives: targeted BCL-2 family inhibitors.

Combining them

• Rapamycin dampens the SASP from cells that senolytics didn't reach.
• Senolytics clear cells that rapamycin was only silencing.
• Sequential or interleaved protocols are being explored.

Trade-offs

• Rapamycin: chronic dosing; systemic exposure; infection risk if immunosuppressive dose reached.
• Senolytics: acute dosing; off-target toxicity (thrombocytopenia with navitoclax); tumour lysis theoretical risk with high senescent burden.

More on this topic

• Rapamycin vs Metformin (for Longevity) — Comparison.
• Senomorphic — Concept.
• Function Health vs InsideTracker — Comparison.
• GrimAge vs DunedinPACE — Comparison.
• NMN vs NR (NAD+ Precursors) — Comparison.

Related entries

Rapamycin, Senolytics, Cellular senescence, Senomorphic vs senolytic.