Cellular senescence in gastrointestinal diseases: from pathogenesis to therapeutics

Abstract

Senescence is a durable cell cycle arrest that can be induced in response to various stress factors, such as telomere erosion, DNA damage or the aberrant activation of oncogenes. In addition to its well-established role as a stress response programme, research has revealed important physiological roles of senescence in nondisease settings, such as embryonic development, wound healing, tissue repair and ageing. Senescent cells secrete various cytokines, chemokines, matrix remodelling proteases and growth factors, a phenotype collectively referred to as the senescence-associated secretory phenotype. These factors evoke immune responses that, depending on the pathophysiological context, can either prevent or even fuel disease and tumorigenesis. Remarkably, even the gut microbiota can influence senescence in various organs. In this Review, we provide an introduction to cellular senescence, addressed particularly to gastroenterologists and hepatologists, and discuss the implications of senescence for the pathogenesis of malignant and nonmalignant gastrointestinal and hepatobiliary diseases. We conclude with an outlook on how modulation of cellular senescence might be used for therapeutic purposes.