Perspective: Targeting the JAK/STAT pathway to fight age-related dysfunction

Abstract

Senescent cells accumulate in a variety of tissues with aging. They can develop a senescence-associated secretory phenotype (SASP) that entails secretion of inflammatory cytokines, chemokines, proteases, and growth factors. These SASP components can alter the microenvironment within tissues and affect the function of neighboring cells, which can eventually lead to local and systemic dysfunction. The JAK pathway is more highly activate in senescent than non-senescent cells. Inhibition of the JAK pathway suppresses the SASP in senescent cells and alleviates age-related tissue dysfunction. Targeting senescent cells could be a promising way to improve healthspan in aged population.

Keywords: Cellular senescence; Frailty; Insulin resistance; Senolytics.