What is Cellular Senescence?Â
Cellular senescence is a state in which cells permanently stop dividing while remaining metabolically active, typically triggered by DNA damage or other cellular stressors. First described by Leonard Hayflick in studies of human fetal fibroblasts, senescence distinguishes non-transformed cells from malignant cells, which can replicate indefinitely. Unlike quiescent cells, which can reenter the cell cycle, or terminally differentiated cells, senescent cells are permanently arrested but exhibit unique features, including chromatin reorganization, altered gene expression, and the senescence-associated secretory phenotype (SASP), a pro-inflammatory profile.The role of senescence is context-dependent, with both protective and harmful effects. It is thought to have evolved as a mechanism to prevent the malignant transformation of damaged cells. However, the accumulation of senescent cells over time contributes to age-related diseases, including cancer, tissue degeneration, and chronic inflammation. Importantly, senescence is not synonymous with aging; while aging reflects a progressive functional decline, senescence occurs throughout life and plays essential roles in embryogenesis, tissue repair, and wound healing. Despite its involvement in aging and pathology, senescence also remains a vital part of normal biological processes.
