A BRIEF OVERVIEW OF INFLAMMATION-INDUCING MECHANISMS IN THE RELATIONSHIP BETWEEN CELL SENESCENCE AND PSORIASIS

<span style="color: rgb(19, 19, 20); font-family: &quot;Inter Var&quot;, Inter, Roboto, Arial, sans-serif; font-size: 14px;">Recent study on cell senescence, a significant factor in the etiology of psoriasis, has garnered attention. This study assessed the correlation between cellular senescence and psoriasis within the context of inflammation. Psoriasis is a dermatological disease that arises in an uncontrolled chronic inflammatory milieu and is characterized by keratinocyte hyperproliferation. Cellular senescence is a condition when cells cease to multiply while remaining metabolically active, typically induced by causes such as DNA damage, oxidative stress, and inflammation. Cellular changes associated with senescence have been observed in psoriatic skin samples. Senescence-prone keratinocytes exhibit senescence-associated secretome phenotypes (SASP) that further accelerate disease progression by secreting factors that exacerbate inflammation. In the case of SASP, senescent cells also produce proinflammatory cytokines, growth factors and proteases, which exacerbate the inflammatory response and cause keratinocyte hyperproliferation. In addition, reactive oxygen species (ROS), mitochondrial dysfunction and responses to DNA damage are other factors that stimulate cellular senescence. Furthermore, senescence continuously interacts with multiple signaling pathways, particularly the RAS-activated phosphatidylinositol 3-kinase (PI3K)/AKT pathway, which contributes to the preservation of the inflammatory milieu linked to psoriasis. PI3K/AKT activation leads to upregulation of senescence markers in keratinocytes, promoting the senescence-associated secretome phenotype (SASP). Moreover, insulin-like growth factor binding protein 2 (IGFBP2) contributes to the disease's pathogenesis via insulin-like growth factor (IGF) signaling, which facilitates keratinocyte hyperproliferation and inflammation. Conversely, it stabilizes p21, a cyclin-dependent kinase inhibitor that inhibits apoptosis in senescent keratinocytes, thereby fostering senescence in psoriasis. Proinflammatory cytokines trigger signaling pathways that induce senescence, resulting in an unregulated cycle of inflammation and senescence. All these factors activate immune cells and maintain psoriasis' chronic inflammatory axis. Thus, cell senescence in psoriasis is crucial to disease development and therapy response. Senescence-targeted treatments, such as senolytics or senescence suppressors, may be regarded as an effective strategy for the treatment of psoriasis. </span> <span style="color: rgb(19, 19, 20); font-family: &quot;Inter Var&quot;, Inter, Roboto, Arial, sans-serif; font-size: 14px;"><br></span> <span style="color: rgb(19, 19, 20); font-family: &quot;Inter Var&quot;, Inter, Roboto, Arial, sans-serif; font-size: 14px;">Keywords: Cell senescence, Psoriasis, Keratinocytes, Inflammation, Senolytics</span>