The mechanisms in glucose metabolism of aging hippocampus

With the intensification of the aging society, the incidence of various neurodegenerative diseases is on the rise. The hippocampus is susceptible to age-related neuronal decline and is the earliest and crucial region affected in the transition from healthy aging to neurodegenerative diseases. Before the diagnosis of neurodegenerative diseases, there is already a decline in brain energy metabolism, with the disruption of energy metabolism serving as the primary mechanism leading to neuronal damage. This triggers complex signaling mechanisms both inside and outside the brain during the aging process. Glucose serves as the primary energy source for brain tissues, and a decrease in glucose metabolism is an early indicator of age-related functional changes in the brain. Therefore, understanding the pathophysiological basis of glucose metabolism in the aging hippocampus, as well as the underlying mechanisms, is crucial in comprehending cognitive aging. Such understanding is integral for early intervention and the mitigation of memory and learning impairments caused by energy metabolism. In this review, we have delved into the characteristics of energy metabolism, focusing specifically on glucose metabolism, as well as exploring the molecular foundations and associated mechanisms present within hippocampal neuronal cells under both normal and aging conditions. Notably, our investigation has highlighted the vital roles played by ALG5 and STT3A, key molecules involved in N-glycosylation, in influencing GLUT expression and the rate of membrane transport, regulating glucose metabolism, and thereby influencing cellular glucose uptake. The exploration of this study direction holds considerable promise for future endeavors.