What are senolytics and how do they work?

Short Answer: Senolytics are drugs that selectively kill senescent (zombie) cells — damaged cells that stop dividing but refuse to die, instead secreting inflammatory factors (SASP) that accelerate aging and disease.

Evidence Level: moderate

Detailed Answer

Cellular senescence is a hallmark of aging. Senescent cells accumulate with age, comprising up to 15% of cells in aged tissues. They secrete the senescence-associated secretory phenotype (SASP) — a cocktail of inflammatory cytokines, matrix metalloproteinases, and growth factors that damages neighboring cells. Senolytics exploit the fact that senescent cells upregulate anti-apoptotic survival pathways (SCAPs). Dasatinib + quercetin (D+Q) is the most studied combination: dasatinib targets tyrosine kinase SCAPs, quercetin targets BCL-2/PI3K survival signaling. Fisetin is an emerging single-agent senolytic (AFFIRM trial, NCT03675724). Key insight: senolytics use intermittent 'hit-and-run' dosing (3 days/month) because senescent cells take weeks to re-accumulate. Mouse studies show D+Q extends healthspan by ~36% even when started in old age.

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