Decoupling glycation from mortality: glucose, but not methylglyoxal, reduces survival in zebra finches

Birds provide a unique model for ageing research, as they exhibit higher mass-adjusted metabolic rates and blood glucose levels than other vertebrate groups, yet demonstrate greater longevity and slower senescence compared to mammals of similar body size. This challenges the "pace of life syndrome" hypothesis, which predicts that high metabolic rates and elevated glucose should correlate with shorter lifespans. While the effects of glucose, glycation, and advanced glycation end-products (AGEs) on ageing are well-documented in humans and the conventional models used in biomedical research, their impact on avian physiology and ageing remains poorly understood. Some evidence suggests that birds possess adaptations mitigating the potential detrimental effects of glucose levels, which are much higher than those of all other vertebrate groups. However, previous studies indicate that elevated glucose predicts reduced lifespan, and protein glycation -varying with age - can influence survival and some fitness-related traits. This implies that glycation or AGE accumulation may have relevant effects on avian longevity. In this study, we experimentally investigated how one year of dietary supplementation with glucose or methylglyoxal affects survival and ageing markers (metabolic rate, flying performance, and beak coloration) in captive zebra finches (Taeniopygia guttata). Our results reveal a significant increase in mortality exclusively in glucose-supplemented birds. Although glucose treatment elevated albumin glycation rate and AGE formation - the latter also observed with methylglyoxal supplementation - these variables did not directly explain the increased mortality in glucose-treated birds, which was absent in methylglyoxal-treated individuals despite similar AGE accumulation. Additionally, we observed some effects on the assessed senescence markers, with an age-related constraint on seasonal metabolic adjustment, and a treatment-influenced age decline in secondary sexual traits expression. These findings support the use of these markers as proxies for senescence in zebra finches. We also discuss alternative mechanisms, independent of the glycation cascade, which may contribute to mortality. A seasonal decline in flight performance, particularly during peak mortality periods, suggests a broader deterioration of health. Thus, although we demonstrate glucose supplementation to be more deleterious than methylglyoxal, the underlying mechanisms for the observed increase in mortality induced by the treatment remain unresolved.