Role of cellular senescence in the pathogenesis of systemic sclerosis

Purpose of review Systemic sclerosis (SSc) is a chronic rheumatic disease that is characterized by immune activation, vasculopathy and fibrosis of the skin and internal organs. It has been proposed that premature onset of ageing pathways and associated senescent changes in cells contribute to the clinical and pathological features of SSc. The aim of this review is to critically review recent insights into the involvement of cellular senescence in SSc. Recent findings Cellular senescence plays a critical role in SSc pathogenesis, particularly involving endothelial cells and fibroblasts. Immunosenescence could also contribute to SSc pathogenesis by direct alteration of cellular functions or indirect promotion of defective immune surveillance. Molecular studies have shed some light on how cellular senescence contributes to fibrosis. Recent and planned proof-of-concept trials using senotherapeutics showed promising results in fibrotic diseases, including SSc. Summary There is increasing evidence implicating cellular senescence in SSc. The mechanisms underlying premature cellular senescence in SSc, and its potential role in pathogenesis, merit further investigation. Emerging drugs targeting senescence-related pathways might be potential therapeutic options for SSc.

Automated summary

This review examines the role of cellular senescence in systemic sclerosis (SSc) and its potential as a therapeutic target. Cellular senescence, particularly in endothelial cells and fibroblasts, plays a critical role in SSc pathogenesis. Immune senescence may also contribute to SSc through direct alteration of cellular functions or indirect promotion of defective immune surveillance. Recent studies have shown promising results in fibrotic diseases, including SSc, using drugs targeting senescence-related pathways.