Ginkgolide B increases healthspan and lifespan of female mice.

Various anti-aging interventions show promise in extending lifespan, but many are ineffective or even harmful to healthspan. Ginkgolide B (GB), derived from Ginkgo biloba, reduces aging-related morbidities such as osteoporosis, yet its effects on healthspan and longevity have not been fully understood. In this study, we found that continuous oral administration of GB to female mice beginning at 20 months of age extended median survival and median lifespan by 30% and 8.5%, respectively. GB treatment also decreased tumor incidence; enhanced muscle quality, physical performance and metabolism; and reduced systemic inflammation and senescence. Single-nucleus RNA sequencing of skeletal muscle tissue showed that GB ameliorated aging-associated changes in cell type composition, signaling pathways and intercellular communication. GB reduced aging-induced Runx1 type 2B myonuclei through the upregulation of miR-27b-3p, which suppresses Runx1 expression. Using functional analyses, we found that Runx1 promoted senescence and cell death in muscle cells. Collectively, these findings suggest the translational potential of GB to extend healthspan and lifespan and to promote healthy aging.