Ginkgolide B as a Candidate Gerotherapeutic: Evidence, Evidentiary Limits, and Translational Requirements

Aging is a systemic process in which redox imbalance, cellular senescence, progenitor-cell dysfunction and chronic inflammation converge on frailty and functional decline, and geroscience seeks compounds that modulate several at once. What is more often missing is an explicit standard for deciding when a compound qualifies as a candidate gerotherapeutic. Ginkgolide B (GB) is a structurally defined diterpene trilactone from Ginkgo biloba and a potent antagonist of the platelet-activating factor receptor. This Review scores GB against ten stated candidacy criteria and grades the supporting evidence. In rodents, purified GB lowers pathological reactive oxygen species and senescence-associated markers, preserves osteogenic and myogenic progenitor function, and improves bone and skeletal muscle outcomes; oral administration begun at 20 months of age increased median lifespan and reduced frailty scores in female C57BL/6 mice. Two criteria are met, three partially met and five unmet: replication, generalizability across sex and genetic background, dose-response and tissue exposure, chronic human safety, and human evidence on any aging-relevant endpoint. Evidence obtained with purified GB is separated throughout from that obtained with terpene-lactone fractions or standardized extracts, since most human data cited in support of GB came from mixtures and may not transfer. Benchmarked against rapamycin, metformin, dasatinib plus quercetin, spermidine and NAD+ precursors, GB is an early-stage candidate: human exposure is intravenous, no longer than fourteen days, and confined to sepsis and acute stroke. The studies that would settle its candidacy are specified; much work remains before GB could be developed as a gerotherapeutic.