Efeitos da senescência celular induzida com D-galactose em células epiteliais tímicas de camundongos

Abstract

Aging is the result of the accumulation of molecular and cellular damage that reduces the functional capacity of tissues and affects the quality of life of the elderly population. In the immune system, this results in immunosenescence, with changes in the immune response and thymic involution, which impair the production of T lymphocytes in the thymus. Thymic involution results from changes in thymic epithelial cells (TEC). The TEC may be susceptible to the effects of free radicals, which favor cellular senescence and, as a result, thymic degeneration as people age. This study aimed to investigate the changes caused by cellular senescence induced by oxidative stress in TEC of mice in vitro. To this end, D-galactose (D-gal), a sugar reducer that induces oxidative stress and promotes cellular senescence, was used in a murine TEC cell line 2BH4. The results demonstrated that treatment with D-gal was effective in inducing senescence, as evidenced by characteristic morphological changes in the cells and a significant increase in the expression of p16, a senescence marker responsible for cell cycle arrest, in addition to a reduction in the number of cells exposed to D-gal. Senescent cells significant increased the expression of the gene for the cytokine TNF-α, reducing a possible participation in the Senescence-Associated Secretory Phenotype (SASP). Regarding cellular function, changes in the composition of the extracellular matrix molecules, fibronectin and laminin, were observed, in addition to significant changes in the expression of the integrin VLA-5, providing possible modifications in cellular interactions with the extracellular matrix, compromising cell adhesion and migration in the thymic microenvironment. These findings suggest that oxidative stress resulting from treatment with D-gal plays an important role in the senescence of these cells, providing a basis for future investigations on age-related thymic involution.