Senolytic Peptide Reference

Senescent cells are cells that have permanently exited the cell cycle but resist apoptosis (programmed death). They accumulate with age and secrete a cocktail of inflammatory cytokines, proteases, and growth factors called the senescence-associated secretory phenotype (SASP). This SASP drives chronic inflammation, tissue dysfunction, and age-related disease. Removing senescent cells in animal models has extended healthspan and reversed age-related pathology — making senolytics one of the most promising aging interventions.

FOXO4-DRI is the most prominent peptide-based senolytic, with its mechanism published in Cell (2017). However, the broader senolytic field includes small molecules (dasatinib + quercetin, fisetin, navitoclax) that are further along in clinical development. Peptide-based senolytics offer mechanistic specificity (FOXO4-DRI targets a single survival axis) but face manufacturing and delivery challenges that small molecules avoid.

Senolytics are designed for intermittent, short-course dosing — not daily supplementation. Senescent cells accumulate slowly (over months to years), so periodic clearance (e.g., a few days of treatment every few months) is the proposed paradigm. This 'hit-and-run' approach minimizes side effect exposure. However, optimal dosing intervals in humans are unknown — all current schedules are extrapolated from animal models.