Moreno Borrallo, A.; Colominas-Ciuro, R.; Colicchio, B.; M'kacher, R.; Allak, A. L.; Criscuolo, F.; Bertile, F.

Birds exhibit longer lifespans than similarly sized mammals, despite having higher mass-adjusted blood glucose levels. This makes them a valuable model for the comparative study of the metabolic and physiological aspects of aging. Circulating glucose contributes to multiple pathological processes, primarily through glycation reactions and the formation of advanced glycation end-products (AGEs), as well as by promoting oxidative stress. These mechanisms are interconnected by feedback loops and play a key role in the development of age-related pathologies. To explore the causal role of glycaemia in avian ageing, we conducted a one-year dietary supplementation experiment in captive zebra finches. Birds received either glucose- or methylglyoxal-enriched water. Previously, we observed that chronic glucose supplementation in zebra finches increased mortality, an effect that did not appear to be mediated by the associated increase in plasma protein glycation or AGE levels. Therefore, the mechanisms underlying increased mortality in the glucose group remained unclear. In the present study, we investigated how glucose and methylglyoxal supplementation affect blood oxidative status and red blood cell telomere dynamics and apoptosis. We found that methylglyoxal supplementation decreased the non-enzymatic antioxidant capacity (OXY) of plasma and increased DNA damage, while glucose supplementation had no significant effect on oxidative stress, although circulating glucose levels influenced oxidative status in a sex-dependent manner. Males exhibited a positive correlation between glucose levels and organic hydroperoxides and protein carbonyls. Additionally, we report, for the first time in birds, a seasonal variation in telomere length, which was more pronounced in glucose-supplemented individuals, yet seemed independent of oxidative status. Apoptosis probability increased with both treatments, particularly with the methylglyoxal supplementation. These results highlight that glucose and methylglyoxal trigger different glucotoxicity-related pathways, with distinct effects on bird health and aging. However, the relationship between glucose supplementation and mortality remains still unclear and warrants further investigation.