Apelin-13 improves post-ischemic cognition by restoring APLN and microglia rhythmicity in aging

Aging increases susceptibility to cerebral ischemia and weakens endogenous protective pathways. We found that Apelin/APLN expression, especially the bioactive Apelin−13 isoform, is markedly reduced in aged mouse brains, and the normal ischemia−induced upregulation of Apelin is blunted. Glial rhythmicity analysis further showed that Apelin expression exhibits clear oscillations in young astrocytes and microglia but becomes disrupted with aging. Apelin−13 supplementation significantly improved post−ischemic learning and memory in aged mice, increased endogenous Apelin-13 levels, reduced TNF−α and IL−6, and enhanced IL−10 expression.These findings indicate that aging disrupts Apelin−dependent neuroprotective and rhythmic pathways, and that Apelin−13 effectively restores inflammatory balance and cognitive recovery after cerebral ischemia, highlighting its potential as a therapeutic strategy for aging−related stroke vulnerability.