Cellular Senescence

Cellular Senescence is a state of irreversible growth arrest that cells enter in response to various stressors, including DNA damage, telomere shortening, oxidative stress, and oncogene activation. Senescent cells undergo profound changes in morphology, gene expression, and metabolism, characterized by increased expression of senescence-associated markers such as p16INK4a, p21CIP1/WAF1, and senescence-associated β-galactosidase (SA-β-gal). While cellular senescence serves as a protective mechanism to prevent the proliferation of damaged or potentially cancerous cells, it also plays a complex role in aging, tissue repair, and age-related diseases. Senescent cells secrete a diverse array of bioactive molecules, collectively termed the senescence-associated secretory phenotype (SASP), which includes pro-inflammatory cytokines, growth factors, extracellular matrix-modifying enzymes, and microRNAs. The SASP can have both beneficial and detrimental effects, contributing to tissue repair and immune surveillance while also promoting chronic inflammation, tissue fibrosis, and age-related pathologies such as cancer, cardiovascular disease, and neurodegeneration. The accumulation of senescent cells with age has been implicated in the aging process and age-related diseases, leading to interest in targeting senescent cells as a potential therapeutic strategy for promoting healthy aging and extending lifespan. Various approaches have been explored to selectively eliminate senescent cells, including senolytic drugs that induce apoptosis in senescent cells, immune-mediated clearance of senescent cells, and targeting specific pathways involved in senescence induction or maintenance.