d-galactose-induced aging and brain mitochondria

Aging is a natural biological phenomenon that leads to a gradual decrease in the biological functions of many organs, namely the brain. Brain aging is associated with a progressive decline of the cognitive function, which is mainly caused by oxidative stress and mitochondrial dysfunction. d-galactose (D-gal) is a reducing sugar that has been widely used to induce an artificial accelerated brain-aging model in rodents. Chronic D-gal administration recapitulates many features of brain aging that resemble natural human brain aging, such as memory impairment and neurodegeneration. This chapter will discuss the mechanisms contributing to D-gal-induced brain aging, particularly cognitive dysfunction. A growing body of evidence has demonstrated that D-gal induces brain aging in a dose-dependent manner (100–500 mg/kg/day for 6–8 weeks) in rodents. The mechanisms underlying brain aging by D-gal include increasing the generation of free radicals and oxidative stress, deterioration of antioxidant system, accumulation of mitochondrial DNA mutations, inhibition of mitochondrial respiratory chain enzymes and adenosine triphosphate production, collapse of mitochondrial membrane potential, neuroinflammation, and apoptosis, as well as reduction of neurogenesis and brain-derived neurotrophic factor. All of these imperfections ultimately result in cognitive impairment.