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In response to many stresses, such as oncogene activation or DNA damage, cells can enter cellular senescence, a state of proliferation arrest accompanied by a senescence-associated secretory phenotype (SASP). Cellular senescence plays a key role in many physiopathological contexts, including cancer, aging and aging-associated diseases, therefore, it is critical to understand how senescence is regulated. Calcium ions (Ca²⁺) recently emerged as pivotal regulators of cellular senescence. However, how Ca²⁺ levels are controlled during this process is barely known. Here, we report that intracellular Ca²⁺ contents increase in response to many senescence inducers in immortalized human mammary epithelial cells (HMECs) and that expression of calbindin 1 (CALB1), a Ca²⁺-binding protein, is upregulated in this context, through the Ca²⁺-dependent calcineurin/NFAT pathway. We further show that overexpression of CALB1 buffers the rise in intracellular Ca²⁺ levels observed in senescent cells. Finally, we suggest that increased expression of Ca²⁺-binding proteins calbindins is a frequent mark of senescent cells. This work thus supports that, together with Ca²⁺channels, Ca²⁺-binding proteins modulate Ca²⁺ levels and flux during cellular senescence. This opens potential avenues of research to better understand the role of Ca²⁺ and of Ca²⁺-binding proteins in regulating cellular senescence.