Cellular senescence is a stress response in which cells permanently stop dividing but remain metabolically active and secrete a mix of inflammatory molecules, growth factors and enzymes known as the senescence associated secretory phenotype, or SASP. Senescence is triggered by diverse insults, including DNA damage, telomere shortening, oncogene activation, oxidative stress and mitochondrial dysfunction. Key pathways include p53 and p16INK4a, which enforce a stable cell cycle arrest.

In young organisms, senescence has beneficial roles. It helps suppress cancer by halting the proliferation of damaged or potentially malignant cells. It also contributes to normal embryonic development, tissue remodeling and wound healing, where senescent cells appear transiently and are then cleared by the immune system.

Problems arise when senescent cells accumulate with age or after chronic stress. Their persistent SASP disrupts tissue structure and function, drives chronic low grade inflammation and alters the behavior of nearby cells. This accumulation has been linked to many age related conditions, including osteoarthritis, atherosclerosis, fibrosis, metabolic dysfunction and neurodegeneration, and it can also impair tissue repair.

Research in mice shows that selectively eliminating senescent cells can delay the onset of age related diseases, improve physical function and extend healthy lifespan. This has led to the development of senolytic drugs that kill senescent cells and senomorphic agents that dampen the SASP without killing the cells. Early preclinical results are promising, and initial human trials target conditions such as idiopathic pulmonary fibrosis and diabetic kidney disease. A central challenge is to remove harmful senescent cells while preserving their beneficial, context dependent roles in development, regeneration and tumor suppression.