Exploring the Communication of the SASP: Dynamic, Interactive, and Adaptive Effects on the Microenvironment

Abstract

Cellular senescence is a complex cell state that can occur during physiological ageing or after exposure to stress signals, regardless of age. It is a dynamic process that continuously evolves in a context-dependent manner. Senescent cells interact with their microenvironment by producing a heterogenous and plastic secretome referred to as the senescence-associated secretory phenotype (SASP). Hence, understanding the cross-talk between SASP and the microenvironment can be challenging due to the complexity of signal exchanges. In this review, we first aim to update the definition of senescence and its associated biomarkers from its discovery to the present day. We detail the regulatory mechanisms involved in the expression of SASP at multiple levels and develop how SASP can orchestrate microenvironment modifications, by focusing on extracellular matrix modifications, neighboring cells’ fate, and intercellular communications. We present hypotheses on how these microenvironmental events may affect dynamic changes in SASP composition in return. Finally, we discuss the various existing approaches to targeting SASP and clarify what is currently known about the biological effects of these modified SASPs on the cellular environment.

Optimal combination of MYCN differential gene and cellular senescence gene predicts adverse outcomes in patients with neuroblastoma

“…Additionally, senescent cells secrete various bioactive cytokines known as SASP ( 34 ). SASP may contribute to shaping the immunosuppressive TME, by inducing immune cells to express high senescence phenotype, such as CD244, and exhausted phenotype like PD-1, TIM-3, et al, aiding tumor cell immune escape ( 11 , 35 – 38 ). It is important to highlight that senescent tumor cells, upon entering the G0 stage, have the ability to evade the cytotoxic effects of traditional chemotherapy drugs that primarily target actively dividing cells ( 14 ).…”

Age-Related Macular Degeneration: A Disease of Cellular Senescence and Dysregulated Immune Homeostasis

“… 10 Although SNCs stop replicating and proliferating, they remain in a metabolically active state, accompanied by the upregulation of numerous inflammatory factors, chemokines, growth factors, etc., collectively termed the Senescence-Associated Secretory Phenotype (SASP). 11 …”

“…The SASP drives the senescence of neighboring cells through autocrine or paracrine mechanisms and exerts deleterious effects in the tissue microenvironment. 11 In the oxygen-induced retinopathy (OIR) mice model, cellular senescence observed in neurons can spread to other cell populations in the retina (such as microglia(MG) cells and ECs), further exacerbating retinal pathology. 29 The SASP produced by SNCs is a major and persistent source of age-related chronic inflammation, with its components varying depending on the disease, triggering factors, and cell type.…”

Silica-coated LiYF4:Yb3+, Tm3+ upconverting nanoparticles are non-toxic and activate minor stress responses in mammalian cells

“…Hallmarks of cellular senescence include changes in cell and nuclear morphologies as well as a profound reorganization of the cytoskeleton and nuclear lamina. 47–49 With the possible exception of cancer cells and wound healing, the induction of cellular senescence by nanomaterials will largely be an undesired outcome. Although NPs may trigger senescence in target cells, only few studies have explored this relationship.…”

“…Aside from cell death, a possible consequence of stress exposure is the induction of cellular senescence. 47 Senescent cells are viable and metabolically active. However, they can damage tissues, organs, and whole organisms through the secretion of a complex mixture of factors, known as the senescence-associated secretome.…”