Cellular senescence, p21, and the path to fibrosis

Senescent cells secrete bioreactive molecules that promote disease, fibrosis, and aging, yet the molecular mechanisms driving the production of these secreted factors remain incompletely understood. In this issue, Papismadov et al (2024) report that p21 (CDKN1A), known to activate the senescence growth arrest, also regulates expression of extracellular matrix components that promote fibrosis, thereby revealing new therapeutic inroads to target fibrosis and age-related pathologies. A recent study shows that p21 (CDKN1A) regulates expression of extracellular matrix components by senescent cells, promoting tissue fibrosis and immune cell infiltration.