Baynes John W
Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina 29208, USA.
Ann N Y Acad Sci. 2002 Apr;959:360-7. doi: 10.1111/j.1749-6632.2002.tb02107.x.
Aging is the outcome of the contest between chemistry and biology in living systems. Chronic, cumulative chemical modifications compromise the structure and function of biomolecules throughout the body. Proteins with long life spans serve as cumulators of exposure to chemical damage, which is detectable in the form of advanced glycation and lipoxidation end products (AGEs, ALEs); amino acids modified by reactive oxygen, chlorine, and nitrogen species; and deamidated and racemized amino acids. Not all of these modifications are oxidative in nature, although oxidative reactions are an important source of age-related damage. Measurements of AGEs and ALEs in proteins are useful for assessing the rate and extent of Maillard reaction damage, but it is the damage to the genome that undoubtedly has the greatest effect on the viability of the organism. The extent of genomic damage represents a balance between the rate of modification and the rate and fidelity of repair. Damage to DNA accumulates not in the form of modified nucleic acids, but as chemically "silent" errors in repair-insertions, deletions, substitutions, transpositions, and inversions in DNA sequences-that affect the expression and structure of proteins. These mutations are random, vary from cell to cell, and are passed forward from one cell generation to another. Although they are not detectable in DNA by conventional analytical techniques, purines and pyrimidines modified by Maillard reaction intermediates may be detectable in urine, and studies on these compounds should provide insight into the role of Maillard reactions of DNA in aging and disease.
衰老乃是生命系统中化学与生物学之间较量的结果。慢性、累积性的化学修饰会损害全身生物分子的结构与功能。寿命较长的蛋白质会累积化学损伤，这些损伤可通过晚期糖基化终产物和脂氧化终产物（AGEs、ALEs）、被活性氧、氯和氮修饰的氨基酸以及脱酰胺和消旋氨基酸的形式检测到。并非所有这些修饰本质上都是氧化反应，尽管氧化反应是与衰老相关损伤的重要来源。对蛋白质中AGEs和ALEs的测量有助于评估美拉德反应损伤的速率和程度，但对基因组的损伤无疑对生物体的生存能力影响最大。基因组损伤的程度代表了修饰速率与修复速率及保真度之间的平衡。DNA的损伤并非以修饰后的核酸形式累积，而是以化学上“沉默”的修复错误形式累积——DNA序列中的插入、缺失、替换、转座和倒位——这些错误会影响蛋白质的表达和结构。这些突变是随机的，在细胞之间各不相同，并从一个细胞世代传递到另一个细胞世代。尽管通过传统分析技术在DNA中无法检测到这些突变，但美拉德反应中间体修饰的嘌呤和嘧啶可能在尿液中被检测到，对这些化合物的研究应能深入了解DNA美拉德反应在衰老和疾病中的作用。
