Healing and hurting: molecular mechanisms, functions, and pathologies of cellular senescence

Abstract

Cellular senescence is a proliferation arrest that is typically irreversible and caused by various cellular stresses, including excess rounds of cell division and cancer-causing genetic alterations. Senescence actively contributes to a tissue-level response to tissue wounding and incipient cancer, healing the tissue and suppressing tumor formation. However, in the long term, the same senescence program may hurt the tissue, thereby contributing to tissue aging. Tumor suppression, wound healing, and aging are each associated with inflammation, and here it is proposed that cellular senescence contributes to a "nonimmune cell" component of the tissue inflammatory response.