CALORIC RESTRICTION DECREASES AGE-DEPENDENT ACCUMULATION OF THE GLYCOXIDATION PRODUCTS, N-EPSILON-(CARBOXYMETHYL)LYSINE AND PENTOSIDINE, IN RAT SKIN COLLAGEN
CALORIC RESTRICTION DECREASES AGE-DEPENDENT ACCUMULATION OF THE GLYCOXIDATION PRODUCTS, N-EPSILON-(CARBOXYMETHYL)LYSINE AND PENTOSIDINE, IN RAT SKIN COLLAGEN
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DOI：
10.1093/gerona/50a.6.b337
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发表时间：
1995-11-01
影响因子：
5.1
通讯作者：
THORPE, SR
中科院分区：
文献类型：
--
作者：
CEFALU, WT;BELLFARROW, AD;THORPE, SR
身体蛋白质的非酶糖化和随后的晚期糖化反应与衰老过程有关，而啮齿动物的热量限制（CR）导致平均寿命和最大寿命增加。我们评价了慢性（25个月）CR对血液蛋白糖化以及皮肤胶原中晚期糖化和氧化（糖氧化）产物N-羧甲基赖氨酸（CML）和戊糖苷的蓄积的影响。从出生开始随意喂食（AL）的Brown-Norway大鼠在4月龄时被分成两个相等的组，并置于AL或CR饮食（CR = AL饮食的60%）。在开始CR后7、13和25个月处死动物队列。尸检时，通过亲和HPLC测定糖化血红蛋白，通过果糖胺测定测定糖化血浆蛋白;通过气相色谱-质谱法分析皮肤胶原蛋白提取物中的CML，并通过反相HPLC分析戊糖苷。糖化血红蛋白，血浆蛋白，皮肤胶原蛋白显着降低（18-33%）CR。在AL和CR动物的裙边胶原蛋白中，CML和戊糖苷的浓度随着年龄的增长而显著增加;然而，CR显著降低了最老大鼠胶原蛋白中CML（25%）、戊糖苷（50%）和荧光（15%）的水平。我们得出结论，CR降低血液和组织蛋白的糖化程度和皮肤胶原中与年龄相关的糖基氧化产物的积累。
Nonenzymatic glycation of body proteins and subsequent advanced glycation reactions have been implicated in the aging process, while caloric restriction (CR) in rodents results in an increase in both mean and maximum life span. We have evaluated the effect of chronic (25 months) CR on glycation of blood proteins and accumulation of advanced glycation and oxidation (glycoxidation) products, N-epsilon-(carboxymethl)lysine (CML), and pentosidine, in skin collagen. Brown-Norway rats, fed ad libitum (AL)from birth, were divided into two equal groups at 4 months of age and placed on AL or CR diets (CR = 60% of AL diet). Cohorts of animals were sacrificed at 7, 13, and 25 months after the initiation of CR. At necropsy glycated hemoglobin was measured by affinity HPLC and glycated plasma protein by the fructosamine assay; extracts of skin collagen were analyzed by gas chromatography-mass spectrometry for CML and by reversed-phase HPLC for pentosidine. Glycation of hemoglobin, plasma proteins, and skin collagen was decreased significantly (18-33%) by CR. Concentrations of CML and pentosidine increased significantly with age in skirt collagen in both AL and CR animals; however, CR significantly reduced levels of CML (25%), pentosidine (50%), and fluorescence (15%) in collagen in the oldest rats. We conclude that CR reduces the extent of glycation of blood and tissue proteins and the age-related accumulation of glycoxidation products in skin collagen.