Senescent Cells Accumulate in Systemic Sclerosis Skin

Abstract

Systemic sclerosis (SSc) is characterized by intractable fibrosis in the skin and internal organs. A unifying paradigm across all forms of fibrosis is the transformation of quiescent progenitor cells into activated myofibroblasts, but the pathways underlying the transformation and persistence of myofibroblasts in SSc remain poorly understood. SSc might be viewed as an accelerated aging phenotype, and patients with SSc prematurely display hallmarks of aging, including telomere attrition, genomic instability, epigenetic alterations, deregulated nutrient sensing, stem cell exhaustion, and mitochondrial dysfunction ( Luckhardt and Thannickal, 2015 Luckhardt T.R. Thannickal V.J. Systemic sclerosis-associated fibrosis: an accelerated aging phenotype?. Curr Opin Rheumatol. 2015; 27: 571-576 Crossref PubMed Scopus (31) Google Scholar ; Tsou et al., 2022 Tsou P.S. Shi B. Varga J. Role of cellular senescence in the pathogenesis of systemic sclerosis. Curr Opin Rheumatol. 2022; 34 (343‒50) Crossref PubMed Scopus (0) Google Scholar ). Cellular senescence is another hallmark of aging. Sustained tissue accumulation of senescent cells is detrimental to organ function owing in part to the senescence-associated secretory phenotype, characterized by secretion of cytokines/chemokines, growth factors, extracellular matrix modifiers, and other substances that promote chronic, sterile inflammation and fibrosis.