Senolytics

Senescent cells resist apoptosis through upregulated pro-survival pathways, and senolytic compounds work by disabling those specific survival pathways in a way that pushes senescent cells — but not healthy cells, which don't rely on the same survival mechanisms — over the threshold into cell death. The concept was validated preclinically by the Mayo Clinic/van Deursen and Kirkland/Scripps labs, whose 2015 identification of dasatinib and quercetin as a senolytic combination ("D+Q") remains the most studied senolytic regimen.

Human evidence for D+Q remains early-stage. A small open-label pilot study (Justice et al., 2019, EBioMedicine) in patients with idiopathic pulmonary fibrosis found the combination reduced some measures of physical dysfunction and reduced senescent cell markers in fat tissue biopsies over a short treatment course — a proof-of-concept biomarker and functional signal, not a large, placebo-controlled outcome trial. Other senolytic candidates, including fisetin, are in earlier or ongoing human trials for various indications.

As of now, no senolytic drug or combination is FDA-approved for any indication, and no trial has demonstrated that clearing senescent cells extends human lifespan or prevents a specific age-related disease at a level that would support routine clinical use. The field is genuinely active — dozens of trials are registered on ClinicalTrials.gov across different senolytic candidates and conditions — but this is early human-stage research, and outside a clinical trial, senolytic use for general anti-aging purposes is an off-label application of drugs (like dasatinib, an approved chemotherapy) whose intermittent low-dose senolytic safety profile is not yet well characterized.