Cellular senescence is a state in which cells permanently stop dividing in response to damage or stress, yet remain metabolically active. It is triggered by factors such as telomere shortening with repeated cell divisions, DNA damage, oxidative stress, oncogene activation and other cellular insults that threaten genomic integrity.

Senescent cells undergo characteristic changes. They activate tumor suppressor pathways, notably p53 and p16, leading to cell cycle arrest. Their chromatin is reorganized and they often express markers such as senescence associated beta galactosidase. Critically, senescent cells secrete a complex mixture of inflammatory cytokines, chemokines, growth factors and proteases known as the senescence associated secretory phenotype, or SASP.

Senescence has a dual role. In youth, it acts as a powerful anticancer mechanism by preventing damaged cells from proliferating. It also contributes to tissue remodeling and wound healing. However, senescent cells accumulate with age because the immune system and tissue clearance mechanisms become less efficient. Persistent SASP signaling can disrupt tissue structure and function, drive chronic inflammation, and promote age related diseases including osteoarthritis, atherosclerosis, pulmonary fibrosis, neurodegeneration and metabolic dysfunction. Paradoxically, SASP factors can in some contexts stimulate neighboring premalignant cells and favor tumor progression.

Research has therefore turned to therapies that selectively eliminate senescent cells, termed senolytics, or that suppress harmful SASP components, termed senomorphics. In animal models, senolytics improve physical function, delay onset of several age related pathologies and extend healthy lifespan. Ongoing work seeks to better define senescence biomarkers, understand tissue specific effects, and develop safe interventions that preserve the beneficial roles of senescence while limiting its contribution to aging and disease.