Longevity & AgingTwo Promising Senolytic Therapies Fail to Replicate in Rigorous Cross-Lab Study
A rigorous cross-laboratory replication study tested two widely cited senolytic interventions—the GLS1 inhibitor BPTES and an anti-PD-1 antibody—in aged mice. Contrary to original reports, neither treatment significantly reduced p16INK4a-positive senescent cell burden in liver, lung, or kidney, nor improved grip strength or external aging phenotypes. In cell culture, BPTES killed senescent cells only at doses toxic to normal proliferating cells, revealing poor selectivity. Genetic deletion of PD-1 similarly failed to lower senescent cell markers. These findings raise serious questions about reproducibility in the senolytic field and emphasize the urgent need for standardized protocols and independent validation before any clinical translation of senolytic therapies.
