Alterações moleculares e celulares provocadas pela indução da senescência celular com D-galactose sobre células epiteliais tímicas humanas

Abstract

Cell senescence is a biological process characterized by the permanent arrest of the cell cycle, often associated with aging and tissue dysfunction. This phenomenon can be triggered by various factors, such as DNA damage, oxidative stress, and metabolic alterations, playing a fundamental role in both physiological processes, such as tissue repair and tumor suppression, and pathological conditions, including aging and the development of chronic diseases. In the immune system, cell senescence can affect the thymus, a primary lymphoid organ responsible for the maturation of T lymphocytes. With aging, the thymus undergoes progressive involution, marked by the reduction of thymic epithelial cells (TECs), increased fibrosis, and infiltration of adipose tissue, ultimately leading to a decline in immune competence. Therefore, understanding the mechanisms involved in TEC senescence is essential to elucidate the factors driving thymic involution and its consequences for immunosenescence. Thus, this study aimed to investigate the molecular and cellular alterations in the cell senescence induced by D-galactose (D-gal) in TECs using traditional cell biology techniques and Raman spectroscopy. Cell viability, proliferation, morphology, and biochemical changes were evaluated in D-gal-treated cells. The results showed that exposure to D-gal significantly reduced cell viability and proliferation, while also causing disorganization of the cellular network, loss of cell adhesion, changes in cell size, morphological flattening, and the presence of vacuoles. Additionally, these alterations were accompanied by an increased presence of apoptotic cells—an unexpected finding, given the typical resistance of senescent cells to apoptosis. Spectroscopic analysis revealed biochemical damage in cellular components such as DNA, proteins, and lipids, highlighting the sensitivity of Raman spectroscopy in detecting senescence-associated changes. This study reinforces the relevance of the D-gal experimental model for investigating cell aging and underscores the need for further research to deepen the understanding of the molecular mechanisms involved and the relationship between cell senescence and apoptosis in the human thymus. Additionally, it highlights Raman spectroscopy as a versatile and promising approach for studying cellular senescence, offering advantages over traditional techniques.