Cellular senescence is a state in which cells permanently stop dividing in response to damage or stress, while remaining metabolically active. It is triggered by factors such as telomere shortening, DNA damage, oxidative stress, oncogene activation and certain chemotherapies. Key pathways involve the tumor suppressors p53 and p16, which enforce a stable cell cycle arrest.

Senescent cells undergo characteristic changes: altered gene expression, chromatin remodeling, resistance to apoptosis and a distinctive secretory profile called the senescence associated secretory phenotype, or SASP. The SASP includes inflammatory cytokines, chemokines, growth factors and matrix remodeling enzymes. These factors can recruit immune cells to clear senescent cells and contribute to tissue repair.

In early life and in acute contexts, senescence is beneficial. It prevents damaged or precancerous cells from proliferating, supports wound healing and contributes to proper embryonic development. However, with age and chronic stress, senescent cells accumulate because immune clearance becomes less efficient. Persisting senescent cells and their SASP can disrupt tissue structure and function, promote chronic inflammation and alter the behavior of neighboring cells.

This accumulation is linked to multiple age related diseases such as osteoarthritis, atherosclerosis, pulmonary fibrosis, type 2 diabetes and neurodegenerative disorders. Animal studies show that selectively eliminating senescent cells using senolytic drugs, or dampening the SASP with senomorphic agents, can delay or alleviate aspects of aging and disease. Current research seeks to refine markers that reliably identify senescent cells, understand context specific SASP profiles and develop targeted therapies that remove or reprogram harmful senescent cells while preserving their protective roles.