Abstract
Aging is a complex natural phenomenon that is manifested by degenerative changes in the structure and function of cells and tissues. D-Galactose-induced aging mice are an artificial accelerated aging model that causes memory and learning impairment, oxidative stress, and neuroinflammation. In this study, we examined the underlying mechanism of an aging mouse model induced by D-galactose. Our behavioral Morris water maze results revealed that D-galactose administration for 2 months significantly induced memory and learning impairment in C57BL/6J mice. High performance liquid chromatography (HPLC) results showed elevated levels of the metabolite methylglyoxal (MG) in D-galactose-induced aging mice. Whether and how D-galactose induces senescence by elevated levels of reactive metabolite MG remain unclear. In our study, MG mainly accumulated through the following two aspects: to increase its source, namely, the triose phosphate produced by the glycolysis pathway, and to reduce its detoxification system, namely, the glyoxalase system. Therefore, elevated MG levels may be one of the causes of brain senescence in D-galactose-induced mice. However, the molecular mechanism of the increased level of the reaction metabolite methylglyoxal requires further exploration.
Highlights
Galactose is generally present in milk as a structural part of lactose
To confirm the inflammatory response induced by advanced glycation end products (AGEs)–receptors for AGEs (RAGEs) interaction in the cortex of the D-galactoseinduced aging mouse model, we examined the ERK, Nuclear factor κB (NF-κB), tumor necrosis factor-α (TNF-α), and IL-1β expression in the mouse cortex by Western blot
We found that elevated MG levels may induce the progressive development of the main characteristics of senescence in D-galactose-induced aging mice
Summary
Galactose is generally present in milk as a structural part of lactose. The main pathway of galactose metabolism in humans involves the conversion of galactose into glucose by galactokinase and galactose-1-phosphate uridyltransferase for glycolysis (Song et al, 1999). Methylglyoxal, which is known as pyruvic aldehyde, is mainly derived from the intermediates of triose phosphate, including G3P and DHAP, during glycolysis; the intermediates are dephosphorylated by non-enzymatic processes or by TPI and MG synthase-catalyzed production (Marie-Julie et al, 2016; Bellahcène et al, 2017). MG accumulation due to reduced TPI activity and impaired MG detoxification resulted in the gradual development of D-galactose-induced aging mice into the core characteristics of aging. Given that elevated MG can generalize the main features of senescence, the possibility that elevated MG levels may be a cause of senescence on D-galactose-induced aging mice is increased
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