Ginkgolide B increase healthspan and lifespan of female mice

Various anti-aging interventions exhibit potential in extending lifespan, yet most of these interventions are inefficacy or even have deleterious effects on healthspan. Ginkgolide B (GB) is a Ginkgo biloba-derived small molecule that reduces aging-related morbidities; however, the effects of GB on healthspan and longevity remain elusive. Here, we report that continuous oral GB administration in mice starting at 20 months extended their lifespan by 20% and reduced tumour incidence. Besides, GB administration significantly improved healthspan evidenced by enhancement in muscle quality, physical performance, grip strength, metabolism, frailty index, systemic inflammation, and senescence. Moreover, GB administration ameliorated aging-related pathologies without any apparent adverse effects. Single-nucleus RNA sequencing (snRNA-seq) revealed that GB improved aging-associated abnormal cell-type composition, intracellular signalling pathways, and cell-cell communication in skeletal muscles. GB also reduced the levels of aging-induced novel Runx1+ type 2B myonuclei, which are associated with apoptotic burden and aging-related signatures. Runx1 derived senescence, as shown by gain- and loss-of-function assays. Together, a new function of GB in extending the healthspan in aging is identified, which contributes to lifespan extension. The senomorphic effects of GB on the multifactorial aging process may provide new prospects for achieving healthy aging and longevity extension.