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Cellular Senescence Drives Zinc Accumulation and Transporter Dysregulation in Intestinal Epithelial Cells

Terrell, K. C.; Choi, S.; Choi, J.; Choi, S.

2026-02-20 cell biology
10.64898/2026.02.19.706872 bioRxiv
Show abstract

Zinc is essential for life, and its regulation is tightly controlled by numerous transporters. As we age, our micronutrient levels, intake, and absorption change. Additionally, senescent cells increase with age and can contribute to the progression of age-related diseases. The study of Zn homeostasis in senescent intestinal cells is a relatively unexplored area that we aimed to investigate. Using two models to induce senescence in intestinal epithelial cells--etoposide treatment and {gamma}-irradiation--we observed that Zn levels increased in the cells, likely due to the upregulation of Zn transporters ZIP4 and ZnT7. This upregulated Zn seems to accumulate in the Golgi apparatus, and when Zn accumulation is blocked through chelation, a rescue effect occurs, marked by a decrease in senescence markers. This research emphasizes the role of Zn in senescent cells and its possible involvement in the development of senescence and the disrupted Zn homeostasis seen with aging.

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