Studies On D-galactose Aging Model And Its Mechanism Of Oxidative Damage And Antagonistic Effects Of α-Lipoic Acid

Aging and age-related diseases have become more and more important social and medical problems with the acceleration of population senescence in the world. Many hypotheses have been proposed to explore the process of aging, however, the underlying mechanisms are yet not well-known. The investigation of the mechanisms of aging and the search for effective agents that can delay the aging process will be beneficial for the human longevity and releasing family and social burdens.Natural old animals are usually used in aging study, however, they are expensive and not easy to obtain. In addition, old animals have high mortality rate and high incidence of tumor, hypertension, diabetes and other diseases. Therefore, developing good aging model is essential and important for studying aging mechanisms and anti-aging agents. D-galactose (D-gal)-induced aging model was first reported in China 20 years ago. This aging model has been continually studied and widely used. However, the underlying mechanism remains largely unknown.The present thesis reports two studies on the D-gal induced aging in different animals. The first study investigated D-gal induced the lifespan shortening in fruit fly and housefly, and the impairment of behavior, changes in central cholinergic and glutamate system function, neuronal apoptosis and the inhibition of proliferation and differentiation of neural stem cells (NSCs) in mice. The second study, based on the mitochondrial free radical theory of aging, mainly investigated the antagonistic effect of R-α-lipoic acid (a-LA), a mitochondrial antioxidant, on D-gal-induced aging in fruit flies, mice, and primary cultured cells of rat cerebral cortex and hippocampus.