ORIGINAL ABSTRACT

Glyphosate potential to induce cellular senescence remains an overlooked aspect of its cytotoxicity mechanism. We investigated glyphosate impact on oxidative and senescence markers in lung and dermal fibroblasts. Primary fibroblasts cultured in the absence or presence of 0.59 and 1.66 µM glyphosate were analyzed after the first (P1) and tenth (P10) passages. Upon glyphosate treatment, protein antioxidant capacity (PAC) was upregulated and cell viability to H2O2 challenge was reduced in P1 and P10 fibroblasts. Non-protein antioxidant capacity (NPAC) was down-regulated, while malondialdehyde, protein carbonyl, and 8-hydroxy-deoxyguanosine levels, p16, p21, p53, HO-1, NRF2, and NQO-1 genes were upregulated in P10 fibroblasts. Telomere length remained unchanged, though proliferative capacity was reduced in these cells. Our findings indicate that prolonged exposure to occupationally relevant glyphosate concentrations increases susceptibility to oxidative stress, accelerating senescence in lung and dermal fibroblasts. Lower antioxidant efficiency is potentially linked to faster senescence progression in dermal fibroblasts.