Aging, Alzheimer’s Disease and Dysfunctional Glycolysis; Similar Effects of Too Much and Too Little

Aging and much related dysfunction can be delayed by decreased glycolysis, however dysfunctional glycolysis appears to play a causative role in Alzheimer’s disease (AD). It is proposed here that this apparent contradiction can be reconciled by suggesting that both over-use and inhibition of the glycolytic enzyme triosephosphate isomerase can limit NADH generation and increase protein glycation. It is also suggested that excessive glycolysis in erythrocytes may provide a source of systemic methylglyoxal and glycated alpha-synuclein, both of which accelerate aging onset and neurodegeneration.