SOX2 and NTF3 expression are associated with taste-bud alterations in aging klotho-deficient mice

Taste dysfunction is commonly associated with aging and accompanied by morphological and molecular alterations in the tongue epithelium. To investigate the mechanisms underlying this phenomenon, we utilized Klotho-deficient (Kl -/-) mice, a model of accelerated aging. The tongue epithelium of Kl -/- mice showed altered muscle organization and increased clear spaces within the muscle compartment. The minor salivary glands displayed acinar cell atrophy. Notably, compared with WT, Kl -/- mice presented a reduced taste bud diameter and decreased expression of key taste receptors, as well as type II taste cells. Importantly, immunohistochemical and western blot analyses revealed decreased expression of SOX2 in taste buds and tongue epithelium. Overexpression of SOX2 significantly upregulated PLCB2, which plays roles in taste bud cell differentiation and function. Conversely, siRNA-mediated knockdown of SOX2 resulted in reduced expression of taste-related genes (Keratin 8, PLCB2, Taste receptors) and decreased expression of NTF3 and BDNF, neurotrophic factors involved in sensory-neural maintenance. Furthermore, SOX2 directly regulated the promoter activity of NTF3, suggesting that SOX2 contributes to taste bud maintenance through transcriptional regulation of NTF3. Together, these findings suggest that altered SOX2 expression is associated with changes in taste-associated proteins and neurotrophic-factors expression in the aging Kl -/- tongue.