Glyoxal induces senescence of human keratinocytes through oxidative stress and activation of the AKT/FOXO3a/p27KIP1 pathway

ABSTRACT: Senescence is a well-known cellular event characterized by specific markers like a permanent cell proliferation arrest and the secretion of messenger molecules forming the Senescence-Associated Secretory Phenotype (SASP). The SASP composition depends on many factors such as the cell type or the nature of the stress that induced senescence. Since the skin constitutes a barrier with the external environment, it is particularly subjected to different types of stresses and thus to premature cellular aging. The dicarbonyl compounds glyoxal and methylglyoxal are precursors of Advanced Glycation End-products (AGEs), known to be a feature of normal and pathological aging. In this study, we have demonstrated that glyoxal provokes oxidative stress by increasing ROS and AGEs levels and can induce senescence in human keratinocytes. An “early-stage” senescence phenotype characterized by a cell cycle arrest mediated by the AKT-FOXO3-p27KIP1 pathway and a “late-stage” senescence maintained by the p16INK4/pRb pathway were evidenced. Moreover, we characterized the resulting secretory phenotype during early senesecence by mass spectrometry. Our study provides evidence that glyoxal can affect keratinocyte function and act as a driver of human skin aging. Hence, senotherapeutics aimed at modulating glyoxal-associated senescence phenotype could be relevant to prevent the aging process in skin.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Keratinocyte

SUBMITTER: Virginie Salnot  

LAB HEAD: Isabelle Petropoulos

PROVIDER: PXD025184 | Pride | 2022-01-03

REPOSITORIES: Pride