Pez cebra: modelado de senescencia en el contexto de la enfermedad y la regeneración

Abstract

Cellular senescence is a natural biological process characterized by a permanent and irreversible state of cellular arrest, mitochondrial alteration, and secretion of senescence-associated phenotype (SASP) components. Several factors can induce senescence, including but not limited to DNA damage, oxidative stress, and neuroinflammation, these factors have also been linked to several disorders such as Alzheimer's, Parkinson's, cancer, among others. The increased presence of senescent cells among different diseases suggests the importance of senescence in the pathophysiology of a great number of disorders, thus the need for different models that could help deepen our understanding of the molecular mechanisms of senescence, identify possible targets for therapeutic interventions, and arising challenges. In addition to in vitro models, most senescent research has come from classical model species, i.e., mouse (Mus musculus) and rat (Rattus norvegicus). However, senescence is highly conserved; different studies have shown that senescent cells seem to accumulate in all vertebrate organisms and that several associated genes show similar expression patterns, opening the door to new vertebrate models. The zebrafish has become a strong emerging model for different diseases, such as cancer, inflammation, neurodegeneration, among others; it shares multiple advantages with classical models, such as well-established genome editing tools and a fully sequenced genome. Additionally, zebrafish exhibit multiple advantages, including high fecundity for robust statistical analysis, external fertilization, and optical transparency that enables powerful imaging capabilities and makes it a versatile model for experimental manipulation and structural visualization. Here we present the zebrafish as a model that can contribute significantly to our understanding of the processes involved in senescence and age-related diseases. ResumenLa senescencia celular es un proceso biológico natural caracterizado por un estado permanente e irreversible de arresto celular, alteraciones mitocondriales y secreción de componentes del fenotipo asociado a la senescencia (SASP). Varios factores pueden inducir la senescencia, incluidos el daño al ADN, estrés oxidante y neuroinflamación; estos factores también se han relacionado con varios trastornos como el Alzheimer, el Parkinson, el cáncer, entre otros. La mayor presencia de células senescentes entre diferentes enfermedades sugiere la importancia de la senescencia en la fisiopatología de un gran número de trastornos, por lo tanto, la necesidad de diferentes modelos que podrían ayudar a profundizar nuestra comprensión de los mecanismos moleculares de la senescencia, identificar posibles objetivos para intervenciones terapéuticas y los desafíos que surgen. Además de los modelos in vitro, la mayoría de las investigaciones senescentes provienen de especies modelo clásicas, es decir, ratón (Mus musculus) y rata (Rattus norvegicus). Sin embargo, la senescencia está muy conservada;