| Exploring healthy longevity and aging of human is playing a crucial role in the area of life sciences and medicine at all times. Because the aging processes is very complex and involves various factors, despite considerable researches over centuries, the exact mechanism underlying aging still remains to be elucidate. Until now, there are hundreds of theories of aging. Those theories from different research points can be summed up to two types:genetic factors and environmental damages on aging. Both of them provide important information of aging from different perspectives, but they have limits to explain the aging. In a word, senescence is a collective consequence of both heredity and environment.Reactive carbonyl species produced in lipid peroxidation and glycation can inevitably result in carbonyl-amino reaction with biomacromolecules in body, and then the products re-arrange. This process leads to the formation of the age pigment-like fluorescent substance which is difficult to be dissolved or degraded. According to the carbonyl stress theory of aging, the crosslink of biomacromolecule induced by carbonyl-amino reaction is the essential course of aging.Carnosine is a natural dipeptide that of highly efficient biological activity. It commonly presents, sometimes at a relatively high concentration (up to 20 mM in human muscle), in mammalian tissues, especially in muscle and brain. The amino group of carnosine can react with reactive carbonyl species thereby inhibiting crosslink of protein caused by toxic carbonyl species. Carnosine play important role in anti-aging of the organism.In this paper we discussed the free radical theory of aging, the glycation theory of aging and carbonyl stress theory of aging that proposed by my tutor professor Yin, based on the biochemical mechanisms of aging pigment formation. We investigated the anti-aging effects of carnosine and studied the reaction mechanisms of carnosine with malondialdehyde (MDA), the typical secondary products in lipid peroxidation.The studies included in the thesis are summarized as follows:In this thesis we study the reaction mechanisms between carnosine and MDA to explore the potential de-carbonylation function of carnosine. The carnosine was incubated with MDA in 0.2M phosphate buffer solution at pH7.4,37℃. The mixture of MDA and carnosine was assayed by high performance liquid chromatography (HPLC), spectrophotometry and spectrofluorometry. The reaction products were assayed by LC/MS. The results indicated that carnosine reacted readily with MDA at supra-physiological condition to form different products, such as a non-fluorescent enamine with an absorption peak at 280 nm (productl) and a lipofuscin-like fluorescent (Excite.392nm/Emission.452nm) 1,4-dihydropyridine(product2). The fluorescence intensity of reaction mixture was in direct proportion to the MDA concentration. Carnosine also greatly inhibited the formation of lipofuscin-like fluorescence induced by MDA reacted with bovine serum albumin (BSA). This study suggested that the reaction of carnosine with MDA may reveal toxic effect of unsaturated carbonyls and provided insight into the reaction mechanism of carnosine in protecting proteins against carbonyl stress.
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