Ponce Mora, A.; Fauzi El-Adhiri, Y.; Guillamin, G.; Martell Vergara, A.; Locascio, A.

Organic germanium, particularly carboxyethyl germanium sesquioxide (Ge 132), has been investigated for decades in relation to diverse biological effects, with a strong emphasis on its antioxidant properties. However, the available literature remains dispersed, encompassing heterogeneous experimental models and endpoints that limit mechanistic interpretation. While antiglycative activity has been described at the biochemical level, its downstream gene regulatory consequences under glycative stress remain inconsistently characterized. Here, we combined systematic review of the literature of experimental studies with targeted molecular analysis in a standardized cellular model. Based on patterns emerging from literature, we focused on pathways associated with glycative stress responses, including carbonyl stress, inflammatory signaling, and autophagy regulation. Gene expression analysis revealed a limited and selective modulation of regulatory pathways under glycative stress conditions, consistent with a context-dependent effect rather than broad transcriptional reprogramming. In parallel, protein analysis showed reduced intracellular accumulation of advanced glycation end products (AGEs) in Ge 132 treated cells under glycative stress conditions. Importantly, these findings support a dissociation between glycative damage reduction and cellular stress response pathways. This combined approach helps interpretation of previously fragmented observations across the literature and highlights gene regulation under glycative stress as a relevant but still unresolved aspect of organogermanium biology.