The secretion of senescent cells is another prominent feature of senescence. Senescent cells typically produce numerous molecules, collectively called the senescent-associated secretory phenotype (SASP), including angiogenic factors, matrix metalloproteinases (MMPs), growth modulators, and various proinflammatory chemokines and cytokines (Coppe
et al. 2010; Kuilman and Peeper
2009). Specifically, there are many signaling pathways participating in the production of SASP, mainly through enhancer remodeling and transcription factors activation, including mammalian target of rapamycin (mTOR), p38MAPK (Freund
et al. 2011; Ito
et al. 2017; Kuilman and Peeper
2009), NF-κB, GATA4, and C/EBPβ (Kang
et al. 2015; Salama
et al. 2014). Various signaling pathways contributing to SASP activation result from the different senescence inducers. Due to DNA damage, type I interferon response is triggered by cytoplasmic chromatin fragments (CCFs), and the inflammasome is activated by damage-associated molecular patterns (DAMPs) instead (Acosta
et al. 2013; Davalos
et al. 2013; Li and Chen
2018). Depending on the pathophysiological context, the senescence response can be useful or harmful. Early in our embryonic development, the SASP can help the morphogenesis of certain structures (Munoz-Espin
et al. 2013) and initiate parturition (Menon
et al. 2019). Besides, when tissue damage occurs, senescent cells can be found in the injured site transiently, where they function in wound healing and regeneration tissue repair, mainly by secretion of certain SASP factors (Ritschka
et al. 2017; Sarig
et al. 2019). One more critical function of SASP is in the process of immunity. Senescent cells can secrete SASP factors through autocrine and paracrine (Acosta
et al. 2013; Coppe
et al. 2010; Kuilman and Peeper
2009), which can activate immune responses, leading to the clearance of senescent cells (Krizhanovsky
et al. 2008; Munoz-Espin and Serrano
2014). Considering the flip side, there are detrimental, pro-aging impacts of senescence because of the SASP. As reported, broad statistics from pharmacological interventions and transgenic rodent models consistently associate senescent cells with a high risk of various age-related pathologies, including tumorigenesis, cardiovascular diseases, and neurodegenerative disorders (Childs
et al. 2017; Song
et al. 2020). Chronic inflammation, mainly due to the SASP development, also termed "inflammaging"
in vivo, is a main trigger for these illnesses (Franceschi and Campisi
2014). More and more senescent cells accumulate in various organs and tissues with age (Bussian
et al. 2018; Childs
et al. 2018), leading to compromised functional ability and more susceptibility to age-related disease.