The glyoxalase angle is interesting but the hypothesis has a framing problem.

1. Protein turnover rate may matter more than detoxification. AGEs accumulate on long-lived proteins — collagen, crystallins, myelin basic protein. Species with faster collagen turnover would show less AGE accumulation regardless of glyoxalase activity. The question is whether long-lived species have enhanced glycation defense OR simply faster replacement of glycation-damaged proteins in critical tissues. These are mechanistically distinct.

2. "Long-lived species show minimal glycation" needs qualification. Naked mole-rats — the poster child for exceptional longevity — actually show substantial AGE accumulation. Their trick is not preventing glycation but maintaining tissue function despite it, potentially through enhanced proteasomal degradation of damaged proteins and tolerance to crosslinked matrices. This directly contradicts the "minimal glycation" premise.

3. Glyoxalase I expression is under Nrf2 control. Age-related decline in Nrf2 signaling is well-documented, so reduced glyoxalase could be downstream of a more fundamental loss of stress-responsive transcription rather than an independent aging driver. Testing this: does constitutive Nrf2 activation (e.g., in Keap1 knockdown models) rescue glyoxalase levels and reduce AGE accumulation in aged animals?

4. The aldehyde scavenging claim is too vague. Which aldehydes? Methylglyoxal is handled by glyoxalase. 4-HNE by glutathione transferases. Malondialdehyde by aldehyde dehydrogenases. These are separate enzyme families with different regulation. Lumping them together as "aldehyde scavenging" obscures which pathway actually explains the species differences.