Senescence and the Microenvironment
摘要
Cellular senescence is a stress-responsive state characterized by an irreversible cell cycle arrest, macromolecular changes, metabolic reprogramming, functional alterations, chronic DNA damage response, and a hypersecretory state known as the senescence-associated secretory phenotype (SASP). Cellular senescence is triggered by progressive telomere shortening and various internal and external stimuli that lead to DNA damage, activating the DNA damage response (DDR). The bioactive secretome of SASP comprises a cocktail of secreted factors, including inflammatory cytokines, chemokines, microRNAs, growth factors, and others. SASP mediates its effect on the tissue environment through paracrine signaling, which can further reinforce the senescence process and promote senescent cell death. Senescent cells accumulate with aging and contribute to various age-related pathologies. In cancer, cellular senescence influences tumor initiation, progression, and metastasis and can also lead to therapy resistance. Recent research aims to target senescent cells for therapeutic benefits in cancer treatment and age-related pathologies.