Inflammaging and Senescence-Associated Secretory Phenotype (SASP) in Psoriasis – A Narrative Review of Potential Mechanisms and Anti-Inflammaging Strategies

Abstract: Psoriasis is a common chronic dermatological disease, affecting approximately 1– 3% of the global population, and is associated with numerous comorbidities, impaired quality of life, and reduced life expectancy compared with the general population. The pathogenesis of psoriasis is complex and multifactorial, involving genetic susceptibility, external environmental factors, and immune system dysregulation. Psoriasis is perceived as a systemic disorder associated with a systemic inflammatory condition. In psoriasis, a chronically activated immune response results in the expression of numerous pro-inflammatory mediators, which enhance and sustain the inflammatory feedback loop, thereby exacerbating cell senescence(definition). Senescent cells adopt a hypersecretory state called senescence-associated secretory phenotype (SASP). Multiple SASP-related mediators are dysregulated in psoriasis, including pro-inflammatory cytokines, chemokines, growth factors, proteases and regulators, soluble or shed receptors and ligands, some of which may serve as biomarkers or therapeutic targets. Therefore, psoriasis is closely associated with immune dysregulation and inflammaging(definition), which refers to a chronic, low-grade inflammatory state with exacerbated cellular senescence. The relationship between psoriasis, inflammation, and cellular senescence is multidirectional, and might be considered in two hypothetical scenarios of cause-and-effect relationship. A persistent pro-inflammatory state might promote cellular senescence and SASP upregulation, which in turn may trigger immunological alterations characteristic of psoriasis, or psoriasis and associated dysregulation of the immune system leading to systemic inflammation and thereby senescence. Hence, it is essential to clarify the mechanisms of inflammaging and the role of SASP in psoriasis. It may support the development of the therapeutic strategies that take into consideration comorbidities and their shared inflammatory background with psoriasis, enabling more precise assessment of the disease. The image A showing inflammaging in psoriasis. Keratinocytes and immune cells are involved in chronic inflammation, mediated by pro-inflammatory mediators and SASP. The image B showing senescence-associated secretory phenotype (SASP). Senescent cells release cytokines, chemokines, growth factors, proteases, regulators and soluble or shed receptors or ligands. These contribute to autocrine/paracrine senescence, inflammation, tissue remodeling, angiogenesis and tumor promotion/suppression. The image C showing potential use in precision dermatology. Individual patient characteristics, external factors like environment and lifestyle and comorbidities are considered. SASP profiling aids in administering patient-tailored treatment based on data integration.Three panels on psoriasis: inflammaging, SASP and precision dermatology use. Keywords: psoriasis, senescence-associated secretory phenotype, inflammaging