NAD⁺ metabolism governs the proinflammatory senescence-associated secretome.

ABSTRACT: Cellular senescence is a stable growth arrest that is implicated in tissue ageing and cancer. Senescent cells are characterized by an upregulation of proinflammatory cytokines, which is termed the senescence-associated secretory phenotype (SASP). NAD⁺ metabolism influences both tissue ageing and cancer. However, the role of NAD⁺ metabolism in regulating the SASP is poorly understood. Here, we show that nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of the NAD⁺ salvage pathway, governs the proinflammatory SASP independent of senescence-associated growth arrest. NAMPT expression is regulated by high mobility group A (HMGA) proteins during senescence. The HMGA-NAMPT-NAD⁺ signalling axis promotes the proinflammatory SASP by

SUBMITTER: Nacarelli T 

PROVIDER: S-EPMC6448588 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature