Klotho: A multifaceted protector in sepsis-induced organ damage and a potential therapeutic target

Sepsis is a life-threatening organ dysfunction associated with a robust systemic inflammatory and immune response to infection. Its pathological consequences lead to multiple organ deficits. Klotho was initially introduced as an antiaging molecule. Its deficiency significantly reduces lifespan, and its overexpression protects against organ injury. It reduces oxidative stress and apoptosis and has anti-inflammatory and antifibrotic properties. In this review, we discuss the underlying mechanisms of sepsis-related klotho down-regulation and the protective role of klotho in sepsis. In developing sepsis-induced multiple organ damage, klotho can modulate multiple downstream signals including nuclear factor-kappa β, mitogen activated protein kinase, and apoptosis. Multiple studies show klotho's protective effects in sepsis through activation of nuclear factor erythroid-related factor 2, Forkhead transcription factor O, and restoration of internal antioxidant activity. The proposed protective action of klotho is a promising therapeutic strategy for managing sepsis and ameliorating its related organ damage.