Altered intercellular communication

Based on the provided sources, intercellular communication and related signaling networks play a critical role in mediating physiological and pathological processes across various biological systems. Methodological frameworks have been established to quantify and analyze these complex cell-cell signaling links, incorporating databases of ligands, receptors, and heteromeric molecular complexes [4]. Additionally, extracellular vesicles (EVs)—including exosomes, microvesicles, and apoptotic bodies—have been increasingly recognized over the past decade for their physiological and pathological functions in cell-to-cell communication, prompting standardized guidelines for their study [2].

Other conserved signaling pathways, such as the insulin/IGF-like signaling (IIS) pathway and mTOR(definition) signaling, are well-documented regulators of cellular growth, organismal metabolism, immunity, and lifespan [5, 10]. Furthermore, metabolic byproducts and second messengers such as reactive oxygen species (ROS) and lipid peroxidation products (e.g., malondialdehyde and 4-hydroxy-2-nonenal) act as signaling mechanisms that influence cell biology, stress responses, and human health [6, 8].

While the fundamental architecture and functional importance of these communication pathways are supported by robust experimental frameworks and consensus guidelines (e.g., MISEV2018 for extracellular vesicles [2]), open questions remain regarding the systems-level integration of global cellular communications and the precise in vivo dynamics of vesicular and ligand-receptor networks in disease progression. The strength of evidence varies by domain: while molecular pathways like IIS and mTOR(definition) are supported by extensive conserved genetic and biochemical data [5, 10], mapping global intercellular networks computationally and standardizing heterogeneous EV preparations represent rapidly evolving areas of ongoing investigation [2, 4].