Brain aging and neurodegenerative diseases: physiological insights from anti-aging protein Klotho

signaling, mitochondrial-redox homeostasis, neuroimmune balance, growth factor signaling, and barrier integrity. Consistent with these physiological roles, reduced Klotho availability is associated with cognitive decline and multiple neurodegenerative disorders. This review positions Klotho as a central determinant of cognitive reserve and neuro-resilience, providing a unifying physiological framework that links systemic homeostasis to brain aging and explains how disruption of Klotho signaling amplifies vulnerability to neurodegenerative disease, whereas its preservation supports lifelong brain integrity.