Cellular senescence: the "hidden driver" in chronic inflammatory skin disorders

Area of Science:

• Dermatology
• Cell Biology
• Immunology

Background:

• Chronic inflammatory skin disorders involve persistent inflammation and impaired barrier function, significantly impacting quality of life.
• While immune dysregulation was traditionally implicated, emerging evidence highlights cellular senescence as a critical factor in disease pathogenesis and progression.
• Cellular senescence is characterized by cell cycle arrest, a senescence-associated secretory phenotype (SASP), mitochondrial dysfunction, and DNA damage.

Purpose of the Study:

• To systematically review the hallmarks, regulatory mechanisms, and inducers of cellular senescence.
• To elucidate the pathological role of cellular senescence in inflammatory skin diseases.
• To evaluate emerging therapeutic strategies targeting senescent cells.

Main Methods:

• Systematic literature review of cellular senescence and inflammatory skin disorders.
• Analysis of the interplay between cellular senescence hallmarks (SASP, mitochondrial dysfunction, DNA damage) and skin inflammation.
• Evaluation of senolytic and senomorphic therapies for inflammatory skin conditions.

Main Results:

• Cellular senescence is a significant risk factor and driver in chronic inflammatory skin diseases.
• Senescence-associated secretory phenotype (SASP) contributes to local and systemic inflammation.
• Targeting senescent cells demonstrates potential for novel therapeutic interventions.

Conclusions:

• Cellular senescence plays a crucial role in the pathophysiology of inflammatory skin disorders.
• Understanding the crosstalk between senescence and skin inflammation can reveal new therapeutic targets.
• Targeting senescent cells offers a promising avenue for improved diagnosis, treatment, and prevention of these debilitating conditions.