Senescent cells and senescence-associated secretory phenotype factors (SASP)

Senescent cells are characterized by a stable exit from the cell cycle in response to various stressors, such as DNA damage, oxidative stress, or oncogene activation (Campisi & d'Adda di Fagagna, 2007). Although they no longer proliferate, these cells remain metabolically active and develop a complex Senescence-Associated Secretory Phenotype (SASP), which consists of pro-inflammatory cytokines, chemokines, growth factors, and matrix metalloproteinases (Coppé et al., 2010). In a physiological context, senescence acts as a potent tumor-suppressive mechanism and facilitates tissue repair and remodeling (Munoz-Espin & Serrano, 2014). However, the chronic accumulation of senescent cells and their persistent SASP during aging drive systemic low-grade inflammation and contribute to the pathogenesis of numerous age-related diseases, including osteoarthritis, idiopathic pulmonary fibrosis, and atherosclerosis (Kirkland & Tchkonia, 2017). Therapeutic interventions, collectively known as senotherapeutics, aim to either selectively eliminate these cells (senolytics) or suppress their harmful secretions (senomorphics) (Childs et al., 2017). By targeting the survival pathways that senescent cells rely on to avoid apoptosis, such as the BCL-2 family or specific kinase networks, these drugs seek to restore tissue homeostasis and extend healthspan (Zhu et al., 2015).

Other names

Cellular senescenceZombie cellsSASPSenescence-associated secretory phenotype

Senolytics induce apoptosis in senescent cells by inhibiting pro-survival pathways (e.g., BCL-2 family proteins), while senomorphics suppress the SASP by modulating signaling pathways like mTOR or NF-kB (Kirkland & Tchkonia, 2017; Laberge et al., 2015).